@article{assiPolatuzumabVedotinCurrent2021,
title = {Polatuzumab {{Vedotin}}: {{Current Role}} and {{Future Applications}} in the {{Treatment}} of {{Patients}} with {{Diffuse Large B-Cell Lymphoma}}},
shorttitle = {Polatuzumab {{Vedotin}}},
author = {Assi, Rita and Masri, Nohad and Dalle, Iman Abou and {El-Cheikh}, Jean and Ghanem, Hady and Bazarbachi, Ali},
year = 2021,
month = mar,
journal = {Clinical Hematology International},
volume = {3},
number = {1},
pages = {21--26},
issn = {2590-0048},
doi = {10.2991/chi.k.210305.001},
urldate = {2026-01-21},
abstract = {Diffuse large B-cell lymphoma (DLBCL) is a biologically and clinically heterogeneous disease. Despite good responses to standard of care frontline chemoimmunotherapy, the prognosis of relapsed/refractory (R/R) patients remains obscured by the possible inadequate responses to salvage therapy, eligibility for autologous transplantation, age and comorbidities. Polatuzumab vedotin is an antibody-drug conjugate formed by a CD79b antibody conjugated to the highly cytotoxic agent monomethyl auristatin E by means of a cleavable linker. Following significant clinical efficacy in R/R DLBCL, polatuzumab vedotin was granted accelerated Food and Drug Administration (FDA) approval in combination with bendamustine plus rituximab for patients who have failed at least two prior therapies. Other clinical studies involving polatuzumab vedotin in combination with other therapy regimens are also under evaluation for previously untreated DLBCL patients. In this article, we review the different phases from the preclinical development of polatuzumab vedotin to studies leading to its first approval, and highlight the potential future roles of this molecule in the treatment landscape of DLBCL.},
pmcid = {PMC8432323},
pmid = {34595463},
file = {/Users/rmorin/Zotero/storage/FWDPNZQT/Assi et al. - 2021 - Polatuzumab Vedotin Current Role and Future Applications in the Treatment of Patients with Diffuse.pdf}
}
@article{camusXPO1CellHematological2017,
title = {{{XPO1}} in {{B}} Cell Hematological Malignancies: From Recurrent Somatic Mutations to Targeted Therapy},
shorttitle = {{{XPO1}} in {{B}} Cell Hematological Malignancies},
author = {Camus, Vincent and Miloudi, Hadjer and Taly, Antoine and Sola, Brigitte and Jardin, Fabrice},
year = 2017,
month = feb,
journal = {Journal of Hematology \& Oncology},
volume = {10},
number = {1},
pages = {47},
issn = {1756-8722},
doi = {10.1186/s13045-017-0412-4},
urldate = {2026-01-21},
abstract = {Many recent publications highlight the large role of the pivotal eukaryotic nuclear export protein exportin-1 (XPO1) in the oncogenesis of several malignancies, and there is emerging evidence that XPO1 inhibition is a key target against cancer. The clinical validation of the pharmacological inhibition of XPO1 was recently achieved with the development of the selective inhibitor of nuclear export compounds, displaying an interesting anti-tumor activity in patients with massive pre-treated hematological malignancies. Recent reports have shown molecular alterations in the gene encoding XPO1 and showed a mutation hotspot (E571K) in the following two hematological malignancies with similar phenotypes and natural histories: primary mediastinal diffuse large B cell lymphoma and classical Hodgkin's lymphoma. Emerging evidence suggests that the mutant XPO1 E571K plays a role in carcinogenesis, and this variant is quantifiable in tumor and plasma cell-free DNA of patients using highly sensitive molecular biology techniques, such as digital PCR and next-generation sequencing. Therefore, it was proposed that the XPO1 E571K variant may serve as a minimal residual disease tool in this setting. To clarify and summarize the recent findings on the role of XPO1 in B cell hematological malignancies, we conducted a literature search to present the major publications establishing the landscape of XPO1 molecular alterations, their impact on the XPO1 protein, their interest as biomarkers, and investigations into the development of new XPO1-targeted therapies in B cell hematological malignancies.},
langid = {english},
keywords = {Exportin,Lymphoma,Minimal residual disease,Targeted therapy,XPO1},
file = {/Users/rmorin/Zotero/storage/RM8HLVIZ/Camus et al. - 2017 - XPO1 in B cell hematological malignancies from recurrent somatic mutations to targeted therapy.pdf}
}
@article{balasubramanianSelectiveInhibitionNuclear2022,
title = {Selective Inhibition of Nuclear Export: A Promising Approach in the Shifting Treatment Paradigms for Hematological Neoplasms},
shorttitle = {Selective Inhibition of Nuclear Export},
author = {Balasubramanian, Suresh Kumar and Azmi, Asfar S. and Maciejewski, Jaroslaw},
year = 2022,
month = mar,
journal = {Leukemia},
volume = {36},
number = {3},
pages = {601--612},
publisher = {Nature Publishing Group},
issn = {1476-5551},
doi = {10.1038/s41375-021-01483-z},
urldate = {2026-01-21},
abstract = {Novel targeted therapeutics alone or in rational combinations are likely to dominate the future management of various hematological neoplasms. However, the challenges currently faced are the molecular heterogeneity in driver lesions and genetic plasticity leading to multiple resistance pathways. Thus, progress has overall been gradual. For example, despite the advent of targeted agents against actionable drivers like FLT3 in acute myeloid leukemia (AML), the prognosis remains suboptimal in newly diagnosed and dismal in the relapsed/refractory (R/R) setting, due to other molecular abnormalities contributing to inherent and acquired treatment resistance. Nuclear export inhibitors are of keen interest because they can inhibit several active tumorigenic processes simultaneously and also synergize with other targeted drugs and chemotherapy. XPO1 (or CRM1, chromosome maintenance region 1) is one of the most studied exportins involved in transporting critical cargoes, including tumor suppressor proteins like p27, p53, and RB1. Apart from the TSP cargo transport and its role in drug resistance, XPO1 inhibition results in retention of master transcription factors essential for cell differentiation, cell survival, and autophagy, rendering cells more susceptible to the effects of other antineoplastic agents, including targeted therapies. This review will dissect the role of XPO1 inhibition in hematological neoplasms, focusing on mechanistic insights gleaned mainly from work with SINE compounds. Future potential combinatorial strategies will be discussed.},
copyright = {2021 The Author(s)},
langid = {english},
keywords = {Drug development,Targeted therapies},
file = {/Users/rmorin/Zotero/storage/JS9P4ZZJ/Balasubramanian et al. - 2022 - Selective inhibition of nuclear export a promising approach in the shifting treatment paradigms for.pdf}
}
@article{freemanMolecularDeterminantsOutcomes2022,
title = {Molecular Determinants of Outcomes in Relapsed or Refractory Mantle Cell Lymphoma Treated with Ibrutinib or Temsirolimus in the {{MCL3001}} ({{RAY}}) Trial},
author = {Freeman, Ciara L. and Pararajalingam, Prasath and Jin, Ling and Balasubramanian, Sriram and Jiang, Aixiang and Xu, Wendan and Grau, Michael and Zapukhlyak, Myroslav and Boyle, Merrill and Hodkinson, Brendan and Schaffer, Michael and Enny, Christopher and Deshpande, Sanjay and Sun, Steven and Vermeulen, Jessica and Morin, Ryan D. and Scott, David W. and Lenz, Georg},
date = {2022-10},
journaltitle = {Leukemia},
shortjournal = {Leukemia},
volume = {36},
number = {10},
eprint = {35963941},
eprinttype = {pmid},
pages = {2479--2487},
issn = {1476-5551},
doi = {10.1038/s41375-022-01658-2},
abstract = {Mantle cell lymphoma (MCL) is a rare, incurable lymphoma subtype characterized by heterogeneous outcomes. To better understand the clinical behavior and response to treatment, predictive biomarkers are needed. Using residual archived material from patients enrolled in the MCL3001 (RAY) study, we performed detailed analyses of gene expression and targeted genetic sequencing. This phase III clinical trial randomized patients with relapsed or refractory MCL to treatment with either ibrutinib or temsirolimus. We confirmed the prognostic capability of the gene expression proliferation assay MCL35 in this cohort treated with novel agents; it outperformed the simplified MCL International Prognostic Index in discriminating patients with different outcomes. Regardless of treatment arm, our data demonstrated that this assay captures the risk conferred by known biological factors, including increased MYC expression, blastoid morphology, aberrations of TP53, and truncated CCND1 3' untranslated region. We showed the negative impact of BIRC3 mutations/deletions on outcomes in this cohort and identified that deletion of chromosome 8p23.3 also negatively impacts survival. Restricted to patients with deletions/alterations in TP53, ibrutinib appeared to abrogate the deleterious impact on outcome. These data illustrate the potential to perform a molecular analysis of predictive biomarkers on routine patient samples that can meaningfully inform clinical practice.},
langid = {english},
keywords = {3' Untranslated Regions,Adenine,Adult,Biological Factors,Humans,Lymphoma Mantle-Cell,Neoplasm Recurrence Local,Piperidines,Pyrazoles,Pyrimidines,Sirolimus}
}
@article{crouchMolecularSubclustersFollicular2022,
title = {Molecular Subclusters of Follicular Lymphoma: A Report from the {{United Kingdom}}’s {{Haematological Malignancy Research Network}}},
shorttitle = {Molecular Subclusters of Follicular Lymphoma},
author = {Crouch, Simon and Painter, Daniel and Barrans, Sharon L. and Roman, Eve and Beer, Philip A. and Cooke, Susanna L. and Glover, Paul and Van Hoppe, Suzan J.L. and Webster, Nichola and Lacy, Stuart E. and Ruiz, Camilo and Campbell, Peter J. and Hodson, Daniel J. and Patmore, Russell and Burton, Cathy and Smith, Alexandra and Tooze, Reuben M.},
date = {2022-11-02},
journaltitle = {Blood Advances},
shortjournal = {Blood Advances},
volume = {6},
number = {21},
pages = {5716--5731},
issn = {2473-9529},
doi = {10.1182/bloodadvances.2021005284},
url = {https://doi.org/10.1182/bloodadvances.2021005284},
urldate = {2024-11-18},
abstract = {Follicular lymphoma (FL) is morphologically and clinically diverse, with mutations in epigenetic regulators alongside t(14;18) identified as disease-initiating events. Identification of additional mutational entities confirms this cancer’s heterogeneity, but whether mutational data can be resolved into mechanistically distinct subsets remains an open question. Targeted sequencing was applied to an unselected population-based FL cohort (n~= 548) with full clinical follow-up (n~= 538), which included 96 diffuse large B-cell lymphoma (DLBCL) transformations. We investigated whether molecular subclusters of FL can be identified and whether mutational data provide predictive information relating to transformation. DNA extracted from FL samples was sequenced with a 293-gene panel representing genes frequently mutated in DLBCL and FL. Three clusters were resolved using mutational data alone, independent of translocation status: FL\_aSHM, with high burden of aberrant somatic hypermutation (aSHM) targets; FL\_STAT6, with high STAT6 \& CREBBP mutation and low aSHM; and FL\_Com, with the absence of features of other subtypes and enriched KMT2D mutation. Analysis of mutation signatures demonstrated differential enrichment of predicted mutation signatures between subgroups and a dominant preference in the FL\_aSHM subgroup for G(C\>T)T and G(C\>T)C transitions consistent with previously defined aSHM-like patterns. Of transformed cases with paired samples, 17 of 26 had evidence of branching evolution. Poorer overall survival (OS) in the aSHM group (P~= .04) was associated with older age; however, overall tumor genetics provided limited information to predict individual patient risk. Our approach identifies 3 molecular subclusters of FL linked to differences in underlying mechanistic pathways. These clusters, which may be further resolved by the inclusion of translocation status and wider mutation profiles, have implications for understanding pathogenesis as well as improving treatment strategies in the future.},
file = {/Users/rmorin/Zotero/storage/LC2Q4NX6/Crouch et al. - 2022 - Molecular subclusters of follicular lymphoma a re.pdf;/Users/rmorin/Zotero/storage/K9SNTHJA/Molecular-subclusters-of-follicular-lymphoma-a.html}
}
@article{pyrzynskaFOXO1PromotesResistance2018,
title = {{FOXO1} promotes resistance of non-{Hodgkin} lymphomas to anti-{CD20}-based therapy},
volume = {7},
issn = {2162-4011},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5927521/},
doi = {10.1080/2162402X.2017.1423183},
abstract = {Diminished overall survival rate of non-Hodgkin lymphoma (NHL) patients treated with a combination regimen of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) has been recently linked to recurrent somatic mutations activating FOXO1. Despite of the clinical relevance of this finding, the molecular mechanism driving resistance to R-CHOP therapy remains largely unknown. Herein, we investigated the potential role of FOXO1 in the therapeutic efficacy of rituximab, the only targeted therapy included in the R-CHOP regimen. We found CD20 transcription is negatively regulated by FOXO1 in NHL cell lines and in human lymphoma specimens carrying activating mutations of FOXO1. Furthermore, both the expression of exogenous mutants of FOXO1 and the inhibition of AKT led to FOXO1 activation in lymphoma cells, increased binding to MS4A1 promoter and diminished CD20 expression levels. In contrast, a disruption of FOXO1 with CRISPR/Cas9 genome-editing (sgFOXO1) resulted in CD20 upregulation, improved the cytotoxicity induced by rituximab and the survival of mice with sgFOXO1 tumors. Accordingly, pharmacological inhibition of FOXO1 activity in primary samples upregulated surface CD20 levels. Importantly, FOXO1 was required for the downregulation of CD20 levels by the clinically tested inhibitors of BTK, SYK, PI3K and AKT. Taken together, these results indicate for the first time that the AKT-unresponsive mutants of FOXO1 are important determinant of cell response to rituximab-induced cytotoxicity, and suggest that the genetic status of FOXO1 together with its transcriptional activity need further attention while designing anti-CD20 antibodies based regimens for the therapy of pre-selected lymphomas.},
number = {5},
urldate = {2024-12-20},
journal = {Oncoimmunology},
author = {Pyrzynska, Beata and Dwojak, Michal and Zerrouqi, Abdessamad and Morlino, Giulia and Zapala, Piotr and Miazek, Nina and Zagozdzon, Agnieszka and Bojarczuk, Kamil and Bobrowicz, Malgorzata and Siernicka, Marta and Machnicki, Marcin M. and Gobessi, Stefania and Barankiewicz, Joanna and Lech-Maranda, Ewa and Efremov, Dimitar G. and Juszczynski, Przemyslaw and Calado, Dinis and Golab, Jakub and Winiarska, Magdalena},
month = jan,
year = {2018},
pmid = {29721381},
pmcid = {PMC5927521},
pages = {e1423183},
file = {PubMed Central Full Text PDF:C\:\\Users\\gbanc\\Zotero\\storage\\2QQ2ZIN9\\Pyrzynska et al. - 2018 - FOXO1 promotes resistance of non-Hodgkin lymphomas to anti-CD20-based therapy.pdf:application/pdf},
}
@article{kober-hasslacherUnsolvedPuzzleCRel2019,
title = {The {Unsolved} {Puzzle} of c-{Rel} in {B} {Cell} {Lymphoma}},
volume = {11},
issn = {2072-6694},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678315/},
doi = {10.3390/cancers11070941},
abstract = {Aberrant constitutive activation of Rel/NF-κB transcription factors is a hallmark of numerous cancers. Of the five Rel family members, c-Rel has the strongest direct links to tumorigenesis. c-Rel is the only member that can malignantly transform lymphoid cells in vitro. Furthermore, c-Rel is implicated in human B cell lymphoma through the frequent occurrence of REL gene locus gains and amplifications. In normal physiology, high c-Rel expression predominates in the hematopoietic lineage and a diverse range of stimuli can trigger enhanced expression and activation of c-Rel. Both expression and activation of c-Rel are tightly regulated on multiple levels, indicating the necessity to keep its functions under control. In this review we meta-analyze and integrate studies reporting gene locus aberrations to provide an overview on the frequency of REL gains in human B cell lymphoma subtypes, namely follicular lymphoma, diffuse large B cell lymphoma, primary mediastinal B cell lymphoma, and classical Hodgkin lymphoma. We also summarize current knowledge on c-Rel expression and protein localization in these human B cell lymphomas and discuss the co-amplification of BCL11A with REL. In addition, we highlight and illustrate key pathways of c-Rel activation and regulation with a specific focus on B cell biology.},
number = {7},
urldate = {2024-12-17},
journal = {Cancers},
author = {Kober-Hasslacher, Maike and Schmidt-Supprian, Marc},
month = jul,
year = {2019},
pmid = {31277480},
pmcid = {PMC6678315},
pages = {941},
file = {PubMed Central Full Text PDF:C\:\\Users\\gbanc\\Zotero\\storage\\TGLI6QIT\\Kober-Hasslacher and Schmidt-Supprian - 2019 - The Unsolved Puzzle of c-Rel in B Cell Lymphoma.pdf:application/pdf},
}
@article{kingUbiquitinLigaseFBXW72013,
title = {The ubiquitin ligase {FBXW7} modulates leukemia-initiating cell activity by regulating {MYC} stability},
volume = {153},
issn = {1097-4172},
doi = {10.1016/j.cell.2013.05.041},
abstract = {Sequencing efforts led to the identification of somatic mutations that could affect the self-renewal and differentiation of cancer-initiating cells. One such recurrent mutation targets the binding pocket of the ubiquitin ligase Fbxw7. Missense FBXW7 mutations are prevalent in various tumors, including T cell acute lymphoblastic leukemia (T-ALL). To study the effects of such lesions, we generated animals carrying regulatable Fbxw7 mutant alleles. Here, we show that these mutations specifically bolster cancer-initiating cell activity in collaboration with Notch1 oncogenes but spare normal hematopoietic stem cell function. We were also able to show that FBXW7 mutations specifically affect the ubiquitylation and half-life of c-Myc protein, a key T-ALL oncogene. Using animals carrying c-Myc fusion alleles, we connected Fbxw7 function to c-Myc abundance and correlated c-Myc expression to leukemia-initiating activity. Finally, we demonstrated that small-molecule-mediated suppression of MYC activity leads to T-ALL remission, suggesting an effective therapeutic strategy.},
language = {eng},
number = {7},
journal = {Cell},
author = {King, Bryan and Trimarchi, Thomas and Reavie, Linsey and Xu, Luyao and Mullenders, Jasper and Ntziachristos, Panagiotis and Aranda-Orgilles, Beatriz and Perez-Garcia, Arianne and Shi, Junwei and Vakoc, Christopher and Sandy, Peter and Shen, Steven S. and Ferrando, Adolfo and Aifantis, Iannis},
month = jun,
year = {2013},
pmid = {23791182},
pmcid = {PMC4146439},
keywords = {Animals, Cell Cycle Proteins, Disease Models, Animal, F-Box Proteins, F-Box-WD Repeat-Containing Protein 7, Hematopoietic Stem Cells, Humans, Mice, Mice, Knockout, Mutation, Missense, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Proto-Oncogene Proteins c-myc, Receptor, Notch1, Tumor Suppressor Protein p53, Ubiquitin-Protein Ligases, Ubiquitination},
pages = {1552--1566},
file = {Full Text:C\:\\Users\\gbanc\\Zotero\\storage\\669DC46T\\King et al. - 2013 - The ubiquitin ligase FBXW7 modulates leukemia-initiating cell activity by regulating MYC stability.pdf:application/pdf},
}
@article{rysFasMutationsNonHodgkins2019,
title = {Fas {Mutations} in {Non}-{Hodgkin}'s {Lymphoma} ({NHL}): {Implications} for {Disease} {Progression} and {Therapeutic} {Resistance}},
volume = {134},
issn = {0006-4971, 1528-0020},
shorttitle = {Fas {Mutations} in {Non}-{Hodgkin}'s {Lymphoma} ({NHL})},
url = {https://ashpublications.org/blood/article/134/Supplement_1/1520/427201/Fas-Mutations-in-NonHodgkins-Lymphoma-NHL},
doi = {10.1182/blood-2019-130602},
abstract = {Introduction: Diffuse large B cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma and standard frontline treatment is carried out with R-CHOP chemotherapy. However, DLBCL remains an extremely heterogenous disease and refractory/relapse events are common. Recent sequencing experiments have found 18\% of relapsed DLBCL contains Fas mutations, an increase from mutations seen at initial diagnosis. Fas receptor (FasR) is a transmembrane protein encoded by the Fas gene that is critical for the induction of extrinsic apoptosis. Once FasR is bound by Fas Ligand expressed on cytotoxic T cells, it initiates the formation of the death-inducing signaling complex and subsequent programmed cell death. Downregulation of FasR expression on B cells has also been a proposed method by which B cell lymphomas are able to evade immune surveillance. Therefore, we hypothesized that dysfunction in Fas signaling contributes to chemotherapy resistance and disease relapse in DLBCL. We used an immune-competent mouse model that can generate aggressive B cell lymphomas (Eμ-Myc) to investigate the role of Fas mutations in lymphomagenesis and response to chemotherapy.
Methods: We designed a breeding program, in which we crossed heterozygous Lpr mice, which harbor a germline mutation in Fas, with Eμ-Myc mice. This led to the development of mice that grow spontaneous Eμ-Myc lymphomas with either FasWT or Fasmut gene alterations, hereafter designated WT and MUT. These mice were analyzed for disease progression and their lymphoma cells were intravenously injected into C57BL/6 mice to create 2nd generation lymphomas. A 3rd generation cohort was developed similarly from injecting 2nd generation lymphoma cells into another group of C57BL/6 mice. 3rd generation mice were treated with components of R-CHOP chemotherapy, namely doxorubicin, vincristine, and cyclophosphamide. Overall and disease-related survival were monitored for all cohorts, and lymph node and spleen tissues were preserved from all 3 generations as formalin-fixed paraffin-embedded (FFPE) blocks. A tissue microarray was created to analyze the tumor microenvironment and elements of extrinsic apoptosis/immune response. Immunohistochemistry staining of the microarray using T cell and lymphoma-related markers is currently ongoing (CD3, CD4, CD8, CD25, FoxP3, TP53, Nfkb, Bcl2).
Results: In the 1st generation, 21/37 WT and 11/18 MUT mice developed lymphoma, with the time to lymphoma death being similar in both groups (170 days versus 140 days, respectively, p =0.32). Of the 32 primary NHLs generated, 3 didn't have sufficient viable cells to perform subsequent experiments. The remaining 29 NHLs were injected into at least two different C57BL/6 mice, with the exception of one who only had enough cells to inject into one mouse. Thus, the second generation included 57 mice transplanted with 29 primary NHLs. Lymphoma development was higher in the MUT cohort (12/37 WT and 14/20 MUT, p=0.011). The all-cause overall survival was not different between both genotypes (p=0.152), but lymphoma specific survival was significantly shorter in the MUT mice (67 days for MUT and 136 days for WT, p=0.026). In the 3rd generation, 93 mice developed lymphoma (54 WT and 39 MUT), of which 15 were used as untreated controls and 78 were treated with components of R-CHOP. Overall, WT mice appeared to have durable responses to therapy, as shown by increased survival when compared to controls across doxorubicin, vincristine, and cyclophosphamide groups (p=0.0147, 0.0406, 0.0321 respectively). However, no difference in survival was seen in the MUT cohort between treated and untreated controls.
Conclusion: Fas mutations may provide survival advantages to lymphoma cells implanted into immune-competent mice. They may also promote resistance to R-CHOP, particularly vincristine, doxorubicin, and cyclophosphamide, but the exact mechanism by which this occurs is unclear. The immune-tumor cell interactions are being investigated by IHC and will be presented.
Disclosures
Johnson: Roche: Consultancy, Employment, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel fees, gifts, and others, Research Funding; Abbvie: Consultancy, Employment, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Consultancy, Honoraria; BMS: Consultancy, Honoraria; BD Biosciences: Other: Provided a significant proportion of the antibodies used in this project free of cost.; Seattle Genetics: Honoraria; Lundbeck: Employment, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel fees, gifts, and others, Research Funding.},
language = {en},
number = {Supplement\_1},
urldate = {2024-12-17},
journal = {Blood},
author = {Rys, Ryan N and Venkataraman, Maanasa and Zeng, Jibin and Mann, Koren Kathleen and Johnson, Nathalie},
month = nov,
year = {2019},
pages = {1520--1520},
}
@article{wohlfartFASCD95Mutations2004,
title = {{FAS} ({CD95}) mutations are rare in gastric {MALT} lymphoma but occur more frequently in primary gastric diffuse large {B}-cell lymphoma},
volume = {164},
issn = {0002-9440},
doi = {10.1016/S0002-9440(10)63195-1},
abstract = {A loss of FAS (CD95) function has been proposed to constitute an important step in early mucosa-associated lymphoid tissue (MALT) lymphoma development and FAS mutations have been recognized in malignant lymphomas, in particular at extranodal sites. Since primary gastric lymphomas frequently exhibit resistance to FAS-mediated apoptosis, we investigated whether FAS is mutated in 18 gastric MALT lymphomas and 28 diffuse large B-cell lymphomas (DLBCL). We detected seven mutations in five lymphomas, one MALT lymphoma and four DLBCL; two DLBCL had two mutations. The MALT lymphoma exhibited a point mutation in the splice donor region of intron 3. Three DLBCL had missense mutations in exon 2, which encodes a signal peptide and a portion of the extracellular FAS ligand-binding domain. One DLBCL carried a point mutation in the splice donor region of intron 8, which would result in exon skipping. Two DLBCL harbored a missense mutation in exon 9, which encodes the intracellular death domain. The two death domain mutations inhibited FAS ligand-induced apoptosis in a dominant-negative mode, when transiently expressed in human T47D breast carcinoma and Jurkat T cells. A signal peptide and an extracellular domain mutation, however, failed to inhibit apoptosis in these transfection assays. They are likely to reduce apoptosis in lymphoma cells solely by a loss of function. In summary, our data show that FAS mutations are rare in primary gastric MALT lymphomas (5.6\%) but occur in a subset of primary gastric DLBCL (14.3\%) and suggest that these mutations contribute to the pathogenesis of gastric lymphomas by rendering lymphocytes resistant to apoptosis.},
language = {eng},
number = {3},
journal = {The American Journal of Pathology},
author = {Wohlfart, Sabine and Sebinger, David and Gruber, Petra and Buch, Judith and Polgar, Doris and Krupitza, Georg and Rosner, Margit and Hengstschläger, Markus and Raderer, Markus and Chott, Andreas and Müllauer, Leonhard},
month = mar,
year = {2004},
pmid = {14982861},
pmcid = {PMC1614721},
keywords = {Apoptosis, Blotting, Western, Cell Line, Tumor, DNA Mutational Analysis, fas Receptor, Humans, Loss of Heterozygosity, Lymphoma, B-Cell, Lymphoma, B-Cell, Marginal Zone, Lymphoma, Large B-Cell, Diffuse, Mutation, Polymorphism, Genetic, Polymorphism, Single-Stranded Conformational, Reverse Transcriptase Polymerase Chain Reaction, Stomach Neoplasms, Transfection},
pages = {1081--1089},
file = {Full Text:C\:\\Users\\gbanc\\Zotero\\storage\\QTZY76EX\\Wohlfart et al. - 2004 - FAS (CD95) mutations are rare in gastric MALT lymphoma but occur more frequently in primary gastric.pdf:application/pdf},
}
@article{gyoryTranscriptionFactorEbf12012,
title = {Transcription factor {Ebf1} regulates differentiation stage-specific signaling, proliferation, and survival of {B} cells},
volume = {26},
issn = {1549-5477},
doi = {10.1101/gad.187328.112},
abstract = {The transcription factor Ebf1 is an important determinant of early B lymphopoiesis. To gain insight into the functions of Ebf1 at distinct stages of differentiation, we conditionally inactivated Ebf1. We found that Ebf1 is required for the proliferation, survival, and signaling of pro-B cells and peripheral B-cell subsets, including B1 cells and marginal zone B cells. The proliferation defect of Ebf1-deficient pro-B cells and the impaired expression of multiple cell cycle regulators are overcome by transformation with v-Abl. The survival defect of transformed Ebf1(fl/fl) pro-B cells can be rescued by the forced expression of the Ebf1 targets c-Myb or Bcl-x(L). In mature B cells, Ebf1 deficiency interferes with signaling via the B-cell-activating factor receptor (BAFF-R)- and B-cell receptor (BCR)-dependent Akt pathways. Moreover, Ebf1 is required for germinal center formation and class switch recombination. Genome-wide analyses of Ebf1-mediated gene expression and chromatin binding indicate that Ebf1 regulates both common and distinct sets of genes in early and late stage B cells. By regulating important components of transcription factor and signaling networks, Ebf1 appears to be involved in the coordination of cell proliferation, survival, and differentiation at multiple stages of B lymphopoiesis.},
language = {eng},
number = {7},
journal = {Genes \& Development},
author = {Györy, Ildiko and Boller, Sören and Nechanitzky, Robert and Mandel, Elizabeth and Pott, Sebastian and Liu, Edison and Grosschedl, Rudolf},
month = apr,
year = {2012},
pmid = {22431510},
pmcid = {PMC3323878},
keywords = {Animals, B-Lymphocytes, Cell Differentiation, Cell Proliferation, Cell Survival, Gene Expression Regulation, Genome-Wide Association Study, Immunoglobulin Heavy Chains, Mice, Mice, Inbred C57BL, Mice, Transgenic, Signal Transduction, Trans-Activators, Transcription, Genetic},
pages = {668--682},
}
@article{schejbelInactivatingBTKMutations2022,
title = {Inactivating {BTK} mutations in large {B}-cell lymphoma in a real-world cohort: {Strong} correlation with {BCL2} translocation},
volume = {3},
issn = {2688-6146},
shorttitle = {Inactivating {BTK} mutations in large {B}-cell lymphoma in a real-world cohort},
doi = {10.1002/jha2.489},
abstract = {Inactivating mutations in Bruton's tyrosine kinase (BTK) in patients with follicular lymphoma (FL) have recently been reported. These mutations were found in BTK inhibitor-treatment naïve patients. Here, we report the BTK mutation status in a real-world cohort of patients with non-Hodgkin lymphoma. We found primary BTK mutations in 7.7\% of patients with large B-cell lymphoma (LBCL) and in 14.1\% of patients with FL. All patients with BTK-mutated LBCL were BCL2 translocation positive, and the correlation between BCL2 translocation and BTK mutation persisted even when patients with known transformation from FL were excluded.},
language = {eng},
number = {3},
journal = {EJHaem},
author = {Schejbel, Lone and Breinholt, Marie Fredslund and Gang, Anne Ortved and Nielsen, Torsten Holm and Pedersen, Lars Møller and Høgdall, Estrid and Nørgaard, Peter},
month = aug,
year = {2022},
pmid = {36051027},
pmcid = {PMC9421985},
keywords = {BTK, molecular pathology, non‐Hodgkin lymphoma},
pages = {936--939},
file = {PubMed Central Full Text PDF:C\:\\Users\\gbanc\\Zotero\\storage\\W8FFCTVJ\\Schejbel et al. - 2022 - Inactivating BTK mutations in large B-cell lymphoma in a real-world cohort Strong correlation with.pdf:application/pdf},
}
@article{balSuperenhancerHypermutationAlters2022,
title = {Super-Enhancer Hypermutation Alters Oncogene Expression in {{B}} Cell Lymphoma},
author = {Bal, Elodie and Kumar, Rahul and Hadigol, Mohammad and Holmes, Antony B. and Hilton, Laura K. and Loh, Jui Wan and Dreval, Kostiantyn and Wong, Jasper C. H. and Vlasevska, Sofija and Corinaldesi, Clarissa and Soni, Rajesh Kumar and Basso, Katia and Morin, Ryan D. and Khiabanian, Hossein and Pasqualucci, Laura and Dalla-Favera, Riccardo},
date = {2022-07},
journaltitle = {Nature},
shortjournal = {Nature},
volume = {607},
number = {7920},
eprint = {35794478},
eprinttype = {pmid},
pages = {808--815},
issn = {1476-4687},
doi = {10.1038/s41586-022-04906-8},
abstract = {Diffuse large B~cell lymphoma (DLBCL) is the most common B cell non-Hodgkin lymphoma and remains incurable in around 40\% of patients. Efforts to sequence the coding genome identified several genes and pathways that are altered in this disease, including potential therapeutic targets1-5. However, the non-coding genome of DLBCL remains largely unexplored. Here we show that active super-enhancers are highly and specifically hypermutated in 92\% of samples from individuals with DLBCL, display signatures of activation-induced cytidine deaminase activity, and are linked to genes that encode B cell developmental regulators and oncogenes. As evidence of oncogenic relevance, we show that the hypermutated super-enhancers linked to the BCL6, BCL2 and CXCR4 proto-oncogenes prevent the binding and transcriptional downregulation of the corresponding target gene by transcriptional repressors, including BLIMP1 (targeting BCL6) and the steroid receptor NR3C1 (targeting BCL2 and CXCR4). Genetic correction of selected mutations restored repressor DNA binding, downregulated target gene expression and led to the counter-selection of cells containing corrected alleles, indicating an oncogenic dependency on the super-enhancer mutations. This pervasive super-enhancer mutational mechanism reveals a major set of genetic lesions deregulating gene expression, which expands the involvement of known oncogenes in DLBCL pathogenesis and identifies new deregulated gene targets of therapeutic relevance.},
langid = {english},
pmcid = {PMC9583699},
keywords = {Down-Regulation,Enhancer Elements Genetic,Gene Expression Regulation Neoplastic,Humans,Lymphoma Large B-Cell Diffuse,mustread,Mutation,Oncogenes,Positive Regulatory Domain I-Binding Factor 1,Proto-Oncogene Proteins c-bcl-2,Proto-Oncogene Proteins c-bcl-6,Receptors CXCR4,Receptors Glucocorticoid,Repressor Proteins},
file = {/Users/rmorin/Zotero/storage/AU9PZ65P/Bal et al. - 2022 - Super-enhancer hypermutation alters oncogene expre.pdf}
}
@article{deschGenotypingCirculatingTumor2020,
title = {Genotyping Circulating Tumor {{DNA}} of Pediatric {{Hodgkin}} Lymphoma},
author = {Desch, Ann-Kathrin and Hartung, Kristin and Botzen, Ante and Brobeil, Alexander and Rummel, Mathias and Kurch, Lars and Georgi, Thomas and Jox, Theresa and Bielack, Stefan and Burdach, Stefan and Classen, Carl Friedrich and Claviez, Alexander and Debatin, Klaus-Michael and Ebinger, Martin and Eggert, Angelika and Faber, Jörg and Flotho, Christian and Frühwald, Michael and Graf, Norbert and Jorch, Norbert and Kontny, Udo and Kramm, Christof and Kulozik, Andreas and Kühr, Joachim and Sykora, Karl-Walter and Metzler, Markus and Müller, Hermann L. and Nathrath, Michaela and Nüßlein, Thomas and Paulussen, Michael and Pekrun, Arnulf and Reinhardt, Dirk and Reinhard, Harald and Rössig, Claudia and Sauerbrey, Axel and Schlegel, Paul-Gerhardt and Schneider, Dominik T. and Scheurlen, Wolfram and Schweigerer, Lothar and Simon, Thorsten and Suttorp, Meinolf and Vorwerk, Peter and Schmitz, Roland and Kluge, Regine and Mauz-Körholz, Christine and Körholz, Dieter and Gattenlöhner, Stefan and Bräuninger, Andreas},
date = {2020-01},
journaltitle = {Leukemia},
shortjournal = {Leukemia},
volume = {34},
number = {1},
eprint = {31431735},
eprinttype = {pmid},
pages = {151--166},
issn = {1476-5551},
doi = {10.1038/s41375-019-0541-6},
abstract = {We used hybrid capture-targeted next-generation sequencing of circulating cell-free DNA (ccfDNA) of pediatric Hodgkin lymphoma (PHL) patients to determine pathogenic mechanisms and assess the clinical utility of this method. Hodgkin-Reed/Sternberg (HRS) cell-derived single nucleotide variants, insertions/deletions, translocations and VH-DH-JH rearrangements were detected in pretherapy ccfDNA of 72 of 96 patients. Number of variants per patient ranged from 1 to 21 with allele frequencies from 0.6 to 42\%. Nine translocation breakpoints were detected. Genes involved in JAK/STAT, NFkB and PI3K signaling and antigen presentation were most frequently affected. SOCS1 variants, mainly deletions, were found in most circulating tumor (ct) DNAs, and seven of the nine translocation breakpoints involved SOCS1. Analysis of VH-DH-JH rearrangements revealed an origin of PHL HRS cells from partially selected germinal center B cells. Amounts of pretherapy ctDNA were correlated with metabolic tumor volumes. Furthermore, in all ccfDNA samples of 43 patients with early response assessment quantitative qPET\,{$<$}\,3, indicative of a favorable clinical course, ctDNA was not detectable. In contrast, in five of six patients with qPET\,{$>$}\,3, indicative of an unfavorable clinical course, ctDNA remained detectable. ccfDNA analysis of PHL is thus a suitable approach to determine pathogenic mechanisms and monitor therapy response.},
langid = {english},
keywords = {Adolescent,Child,Child Preschool,Circulating Tumor DNA,Female,Genotype,Hodgkin Disease,Humans,Male},
file = {/Users/rmorin/Zotero/storage/ZAV2XQXF/Desch et al. - 2020 - Genotyping circulating tumor DNA of pediatric Hodg.pdf}
}
@article{rossiAberrantSomaticHypermutation2006,
title = {Aberrant somatic hypermutation in transformation of follicular lymphoma and chronic lymphocytic leukemia to diffuse large {B}-cell lymphoma},
volume = {91},
issn = {1592-8721},
abstract = {The molecular mechanisms involved in histologic transformation of follicular lymphoma (FL) and B-chronic lymphocytic leukemia (B-CLL) to diffuse large B-cell lymphoma (DLBCL) are heterogeneous and largely unknown. Here we explored whether aberrant somatic hypermutation, leading to the acquisition of new mutations in PIM-1, PAX-5, RhoH/TTF and c-MYC genes, is involved in transformation from FL or B-CLL to DLBCL. Eighteen sequential pairs of FL/DLBCL (n=9) and B-CLL/DLBCL (n=9) were investigated. Our findings demonstrate that acquisition of novel mutations due to aberrant somatic hypermutation was associated with DLBCL transformation in 5/9 (55.5\%) cases of FL and 2/9 (22.2\%) cases of B-CLL.},
language = {eng},
number = {10},
journal = {Haematologica},
author = {Rossi, Davide and Berra, Eva and Cerri, Michaela and Deambrogi, Clara and Barbieri, Caterina and Franceschetti, Silvia and Lunghi, Monia and Conconi, Annarita and Paulli, Marco and Matolcsy, Andràs and Pasqualucci, Laura and Capello, Daniela and Gaidano, Gianluca},
month = oct,
year = {2006},
pmid = {17018394},
keywords = {Humans, Gene Frequency, Lymphoma, B-Cell, Cell Transformation, Neoplastic, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Follicular, Somatic Hypermutation, Immunoglobulin, Gene Rearrangement, B-Lymphocyte},
pages = {1405--1409},
}
@article{barariaCathepsinAlterationsInduce2020,
title = {Cathepsin {S} {Alterations} {Induce} a {Tumor}-{Promoting} {Immune} {Microenvironment} in {Follicular} {Lymphoma}},
volume = {31},
issn = {2211-1247},
doi = {10.1016/j.celrep.2020.107522},
abstract = {Tumor cells orchestrate their microenvironment. Here, we provide biochemical, structural, functional, and clinical evidence that Cathepsin S (CTSS) alterations induce a tumor-promoting immune microenvironment in follicular lymphoma (FL). We found CTSS mutations at Y132 in 6\% of FL (19/305). Another 13\% (37/286) had CTSS amplification, which was associated with higher CTSS expression. CTSS Y132 mutations lead to accelerated autocatalytic conversion from an enzymatically inactive profrom to active CTSS and increased substrate cleavage, including CD74, which regulates major histocompatibility complex class II (MHC class II)-restricted antigen presentation. Lymphoma cells with hyperactive CTSS more efficiently activated antigen-specific CD4+ T cells in vitro. Tumors with hyperactive CTSS showed increased CD4+ T cell infiltration and proinflammatory cytokine perturbation in a mouse model and in human FLs. In mice, this CTSS-induced immune microenvironment promoted tumor growth. Clinically, patients with CTSS-hyperactive FL had better treatment outcomes with standard immunochemotherapies, indicating that these immunosuppressive regimens target both the lymphoma cells and the tumor-promoting immune microenvironment.},
language = {eng},
number = {5},
journal = {Cell Reports},
author = {Bararia, Deepak and Hildebrand, Johannes A. and Stolz, Sebastian and Haebe, Sarah and Alig, Stefan and Trevisani, Christopher P. and Osorio-Barrios, Francisco and Bartoschek, Michael D. and Mentz, Michael and Pastore, Alessandro and Gaitzsch, Erik and Heide, Michael and Jurinovic, Vindi and Rautter, Katharina and Gunawardana, Jay and Sabdia, Muhammed B. and Szczepanowski, Monika and Richter, Julia and Klapper, Wolfram and Louissaint, Abner and Ludwig, Christina and Bultmann, Sebastian and Leonhardt, Heinrich and Eustermann, Sebastian and Hopfner, Karl-Peter and Hiddemann, Wolfgang and von Bergwelt-Baildon, Michael and Steidl, Christian and Kridel, Robert and Tobin, Joshua W. D. and Gandhi, Maher K. and Weinstock, David M. and Schmidt-Supprian, Marc and Sárosi, Menyhárt B. and Rudelius, Martina and Passerini, Verena and Mautner, Josef and Weigert, Oliver},
month = may,
year = {2020},
pmid = {32330423},
keywords = {Animals, Humans, Antigen Presentation, Mice, Cytokines, Lymphoma, Follicular, follicular lymphoma, Tumor Microenvironment, Antigens, Differentiation, B-Lymphocyte, antigen processing and presentation, cathepsin S, Cathepsins, cysteine-protease, Histocompatibility Antigens Class II, immune microenvironment, Immunosuppression Therapy, T cell activation, Lymphopedia},
pages = {107522},
file = {Full Text:/Users/rmorin/Zotero/storage/D9BZZT9L/Bararia et al. - 2020 - Cathepsin S Alterations Induce a Tumor-Promoting I.pdf:application/pdf},
}
@article{maSubtypespecificCooccurringGenetic2022,
title = {Subtype-specific and co-occurring genetic alterations in {B}-cell non-{Hodgkin} lymphoma},
volume = {107},
issn = {1592-8721},
doi = {10.3324/haematol.2020.274258},
abstract = {B-cell non-Hodgkin lymphoma (B-NHL) encompasses multiple clinically and phenotypically distinct subtypes of malignancy with unique molecular etiologies. Common subtypes of B-NHL, such as diffuse large B-cell lymphoma, have been comprehensively interrogated at the genomic level, but rarer subtypes, such as mantle cell lymphoma, remain less extensively characterized. Furthermore, multiple B-NHL subtypes have thus far not been comprehensively compared using the same methodology to identify conserved or subtype-specific patterns of genomic alterations. Here, we employed a large targeted hybrid-capture sequencing approach encompassing 380 genes to interrogate the genomic landscapes of 685 B-NHL tumors at high depth, including diffuse large B-cell lymphoma, mantle cell lymphoma, follicular lymphoma, and Burkitt lymphoma. We identified conserved hallmarks of B-NHL that were deregulated in the majority of tumors from each subtype, including frequent genetic deregulation of the ubiquitin proteasome system. In addition, we identified subtype-specific patterns of genetic alterations, including clusters of co-occurring mutations and DNA copy number alterations. The cumulative burden of mutations within a single cluster were more discriminatory of B-NHL subtypes than individual mutations, implicating likely patterns of genetic cooperation that contribute to disease etiology. We therefore provide the first cross-sectional analysis of mutations and DNA copy number alterations across major B-NHL subtypes and a framework of co-occurring genetic alterations that deregulate genetic hallmarks and likely cooperate in lymphomagenesis.},
language = {eng},
number = {3},
journal = {Haematologica},
author = {Ma, Man Chun John and Tadros, Saber and Bouska, Alyssa and Heavican, Tayla and Yang, Haopeng and Deng, Qing and Moore, Dalia and Akhter, Ariz and Hartert, Keenan and Jain, Neeraj and Showell, Jordan and Ghosh, Sreejoyee and Street, Lesley and Davidson, Marta and Carey, Christopher and Tobin, Joshua and Perumal, Deepak and Vose, Julie M. and Lunning, Matthew A. and Sohani, Aliyah R. and Chen, Benjamin J. and Buckley, Shannon and Nastoupil, Loretta J. and Davis, R. Eric and Westin, Jason R. and Fowler, Nathan H. and Parekh, Samir and Gandhi, Maher and Neelapu, Sattva and Stewart, Douglas and Bhalla, Kapil and Iqbal, Javeed and Greiner, Timothy and Rodig, Scott J. and Mansoor, Adnan and Green, Michael R.},
month = mar,
year = {2022},
pmid = {33792219},
pmcid = {PMC8883549},
keywords = {Humans, Mutation, Adult, Lymphoma, Large B-Cell, Diffuse, Burkitt Lymphoma, Lymphoma, Follicular, Cross-Sectional Studies},
pages = {690--701},
file = {Full Text:/Users/rmorin/Zotero/storage/3K8ZEXTA/Ma et al. - 2022 - Subtype-specific and co-occurring genetic alterati.pdf:application/pdf},
}
@article{laurentFollicularLymphomaComprises2024,
title = {Follicular lymphoma comprises germinal center-like and memory-like molecular subtypes with prognostic significance},
journal = {Blood},
author = {Laurent, Camille and Trisal, Preeti and Tesson, Bruno and Seth, Sahil and Beyou, Alicia and Roulland, Sandrine and Lesne, Bastien and Van Acker, Nathalie and Cerapio, Juan-Pablo and Chartier, Loic and Guille, Arnaud and Stokes, Matthew and Huang, Chris and Huet, Sarah and Gandhi, Anita and Morschauser, Franck and Xerri, Luc},
month = oct,
year = {2024},
}
@article{novakWholeexomeAnalysisReveals2015,
title = {Whole-exome analysis reveals novel somatic genomic alterations associated with outcome in immunochemotherapy-treated diffuse large {B}-cell lymphoma},
volume = {5},
copyright = {2015 The Author(s)},
issn = {2044-5385},
url = {https://www.nature.com/articles/bcj201569},
doi = {10.1038/bcj.2015.69},
abstract = {Lack of remission or early relapse remains a major clinical issue in diffuse large B-cell lymphoma (DLBCL), with 30\% of patients failing standard of care. Although clinical factors and molecular signatures can partially predict DLBCL outcome, additional information is needed to identify high-risk patients, particularly biologic factors that might ultimately be amenable to intervention. Using whole-exome sequencing data from 51 newly diagnosed and immunochemotherapy-treated DLBCL patients, we evaluated the association of somatic genomic alterations with patient outcome, defined as failure to achieve event-free survival at 24 months after diagnosis (EFS24). We identified 16 genes with mutations, 374 with copy number gains and 151 with copy number losses that were associated with failure to achieve EFS24 (P{\textless}0.05). Except for FOXO1 and CIITA, known driver mutations did not correlate with EFS24. Gene losses were localized to 6q21-6q24.2, and gains to 3q13.12-3q29, 11q23.1-11q23.3 and 19q13.12-19q13.43. Globally, the number of gains was highly associated with poor outcome (P=7.4 × 10−12) and when combined with FOXO1 mutations identified 77\% of cases that failed to achieve EFS24. One gene (SLC22A16) at 6q21, a doxorubicin transporter, was lost in 54\% of EFS24 failures and our findings suggest it functions as a doxorubicin transporter in DLBCL cells.},
language = {en},
number = {8},
urldate = {2024-11-15},
journal = {Blood Cancer Journal},
author = {Novak, A. J. and Asmann, Y. W. and Maurer, M. J. and Wang, C. and Slager, S. L. and Hodge, L. S. and Manske, M. and Price-Troska, T. and Yang, Z.-Z. and Zimmermann, M. T. and Nowakowski, G. S. and Ansell, S. M. and Witzig, T. E. and McPhail, E. and Ketterling, R. and Feldman, A. L. and Dogan, A. and Link, B. K. and Habermann, T. M. and Cerhan, J. R.},
month = aug,
year = {2015},
note = {Publisher: Nature Publishing Group},
keywords = {Cancer genomics, Haematological cancer, LCOR},
pages = {e346--e346},
file = {Full Text PDF:/Users/rmorin/Zotero/storage/IIMWS3Y4/Novak et al. - 2015 - Whole-exome analysis reveals novel somatic genomic.pdf:application/pdf},
}
@article{futrealCensusHumanCancer2004,
title = {A census of human cancer genes},
volume = {4},
issn = {1474-175X},
doi = {10.1038/nrc1299},
abstract = {A central aim of cancer research has been to identify the mutated genes that are causally implicated in oncogenesis (‘cancer genes’). After two decades of searching, how many have been identified and how do they compare to the complete gene set that has been revealed by the human genome sequence? We have conducted a ‘census’ of cancer genes that indicates that mutations in more than 1\% of genes contribute to human cancer. The census illustrates striking features in the types of sequence alteration, cancer classes in which oncogenic mutations have been identified and protein domains that are encoded by cancer genes.},
language = {eng},
number = {3},
journal = {Nature Reviews. Cancer},
author = {Futreal, P. Andrew and Coin, Lachlan and Marshall, Mhairi and Down, Thomas and Hubbard, Timothy and Wooster, Richard and Rahman, Nazneen and Stratton, Michael R.},
month = mar,
year = {2004},
pmid = {14993899},
pmcid = {PMC2665285},
keywords = {Genes, Genome, Human, Humans, Mutation, Neoplasms, Oncogenes},
pages = {177--183},
file = {Accepted Version:/Users/rmorin/Zotero/storage/CCYI8YXU/Futreal et al. - 2004 - A census of human cancer genes.pdf:application/pdf},
}
@article{shyrFLAGSFrequentlyMutated2014,
title = {{FLAGS}, frequently mutated genes in public exomes},
volume = {7},
issn = {1755-8794},
doi = {10.1186/s12920-014-0064-y},
abstract = {BACKGROUND: Dramatic improvements in DNA-sequencing technologies and computational analyses have led to wide use of whole exome sequencing (WES) to identify the genetic basis of Mendelian disorders. More than 180 novel rare-disease-causing genes with Mendelian inheritance patterns have been discovered through sequencing the exomes of just a few unrelated individuals or family members. As rare/novel genetic variants continue to be uncovered, there is a major challenge in distinguishing true pathogenic variants from rare benign mutations.
METHODS: We used publicly available exome cohorts, together with the dbSNP database, to derive a list of genes (n = 100) that most frequently exhibit rare ({\textless}1\%) non-synonymous/splice-site variants in general populations. We termed these genes FLAGS for FrequentLy mutAted GeneS and analyzed their properties.
RESULTS: Analysis of FLAGS revealed that these genes have significantly longer protein coding sequences, a greater number of paralogs and display less evolutionarily selective pressure than expected. FLAGS are more frequently reported in PubMed clinical literature and more frequently associated with diseased phenotypes compared to the set of human protein-coding genes. We demonstrated an overlap between FLAGS and the rare-disease causing genes recently discovered through WES studies (n = 10) and the need for replication studies and rigorous statistical and biological analyses when associating FLAGS to rare disease. Finally, we showed how FLAGS are applied in disease-causing variant prioritization approach on exome data from a family affected by an unknown rare genetic disorder.
CONCLUSIONS: We showed that some genes are frequently affected by rare, likely functional variants in general population, and are frequently observed in WES studies analyzing diverse rare phenotypes. We found that the rate at which genes accumulate rare mutations is beneficial information for prioritizing candidates. We provided a ranking system based on the mutation accumulation rates for prioritizing exome-captured human genes, and propose that clinical reports associating any disease/phenotype to FLAGS be evaluated with extra caution.},
language = {eng},
journal = {BMC medical genomics},
author = {Shyr, Casper and Tarailo-Graovac, Maja and Gottlieb, Michael and Lee, Jessica J. Y. and van Karnebeek, Clara and Wasserman, Wyeth W.},
month = dec,
year = {2014},
pmid = {25466818},
pmcid = {PMC4267152},
keywords = {Biomarkers, Child, Preschool, Databases, Factual, Datasets as Topic, Exome, Exome Sequencing, Exome Variant Server, Female, Gene Expression Profiling, Gene Frequency, Humans, Mutation, Oligonucleotide Array Sequence Analysis, Open Reading Frame Length, Rare Variant, Sequence Analysis, RNA, Whole Exome Sequencing},
pages = {64},
file = {Full Text:/Users/rmorin/Zotero/storage/275QZ9A9/Shyr et al. - 2014 - FLAGS, frequently mutated genes in public exomes.pdf:application/pdf},
}
@article{miloudiXPO1E571KMutationModifies2020,
title = {{{XPO1E571K Mutation Modifies Exportin}} 1 {{Localisation}} and {{Interactome}} in {{B-cell Lymphoma}}},
author = {Miloudi, Hadjer and Bohers, Élodie and Guillonneau, François and Taly, Antoine and Gibouin, Vincent Cabaud and Viailly, Pierre-Julien and Jego, Gaëtan and Grumolato, Luca and Jardin, Fabrice and Sola, Brigitte},
date = {2020-09-30},
journaltitle = {Cancers},
shortjournal = {Cancers (Basel)},
volume = {12},
number = {10},
eprint = {33007990},
eprinttype = {pmid},
pages = {2829},
issn = {2072-6694},
doi = {10.3390/cancers12102829},
abstract = {The XPO1 gene encodes exportin 1 (XPO1) that controls the nuclear export of cargo proteins and RNAs. Almost 25\% of primary mediastinal B-cell lymphoma (PMBL) and classical Hodgkin lymphoma (cHL) cases harboured a recurrent XPO1 point mutation (NM\_003400, chr2:g61718472C{$>$}T) resulting in the E571K substitution within the hydrophobic groove of the protein, the site of cargo binding. We investigated the impact of the XPO1E571K mutation using PMBL/cHL cells having various XPO1 statuses and CRISPR-Cas9-edited cells in which the E571K mutation was either introduced or knocked-out. We first confirmed that the mutation was present in both XPO1 mRNA and protein. We observed that the mutation did not modify the export capacity but rather the subcellular localisation of XPO1 itself. In particular, mutant XPO1 bound to importin β1 modified the nuclear export/import dynamics of relevant cargoes.},
langid = {english},
pmcid = {PMC7600770},
keywords = {B-cell lymphoma,CRISPR–Cas9,importin β1,indirect immunofluorescence,nuclear export,nuclear import,proteomics,proximity ligation assay,XPO1/CRM1},
file = {/Users/rmorin/Zotero/storage/IQBJHDK5/Miloudi et al. - 2020 - XPO1E571K Mutation Modifies Exportin 1 Localisatio.pdf}
}
@article{asmarGenomewideProfilingIdentifies2013,
title = {Genome-Wide Profiling Identifies a {{DNA}} Methylation Signature That Associates with {{TET2}} Mutations in Diffuse Large {{B-cell}} Lymphoma},
author = {Asmar, Fazila and Punj, Vasu and Christensen, Jesper and Pedersen, Marianne T. and Pedersen, Anja and Nielsen, Anders B. and Hother, Christoffer and Ralfkiaer, Ulrik and Brown, Peter and Ralfkiaer, Elisabeth and Helin, Kristian and Grønbæk, Kirsten},
date = {2013-12},
journaltitle = {Haematologica},
shortjournal = {Haematologica},
volume = {98},
number = {12},
eprint = {23831920},
eprinttype = {pmid},
pages = {1912--1920},
issn = {1592-8721},
doi = {10.3324/haematol.2013.088740},
abstract = {The discovery that the Ten-Eleven Translocation (TET) hydroxylases cause DNA demethylation has fundamentally changed the notion of how DNA methylation is regulated. Clonal analysis of the hematopoetic stem cell compartment suggests that TET2 mutations can be early events in hematologic cancers and recent investigations have shown TET2 mutations in diffuse large B-cell lymphoma. However, the detection rates and the types of TET2 mutations vary, and the relation to global methylation patterns has not been investigated. Here, we show TET2 mutations in 12 of 100 diffuse large B-cell lymphomas with 7\% carrying loss-of-function and 5\% carrying missense mutations. Genome-wide methylation profiling using 450K Illumina arrays identified 315 differentially methylated genes between TET2 mutated and TET2 wild-type cases. TET2 mutations are primarily associated with hypermethylation within CpG islands (70\%; P{$<$}0.0001), and at CpG-rich promoters (60\%; P{$<$}0.0001) of genes involved in hematopoietic differentiation and cellular development. Hypermethylated loci in TET2 mutated samples overlap with the bivalent (H3K27me3/H3K4me3) silencing mark in human embryonic stem cells (P=1.5×10(-30)). Surprisingly, gene expression profiling showed that only 11\% of the hypermethylated genes were down-regulated, among which there were several genes previously suggested to be tumor suppressors. A meta-analysis suggested that the 35 hypermethylated and down-regulated genes are associated with the activated B-cell-like type of diffuse large B-cell lymphoma in other studies. In conclusion, our data suggest that TET2 mutations may cause aberrant methylation mainly of genes involved in hematopoietic development, which are silenced but poised for activation in human embryonic stem cells.},
langid = {english},
pmcid = {PMC3856967},
keywords = {Aged,Dioxygenases,DNA Methylation,DNA-Binding Proteins,Female,Gene Expression Profiling,Genome-Wide Association Study,Humans,Lymphoma Large B-Cell Diffuse,Male,Middle Aged,Mutation,Proto-Oncogene Proteins},
file = {/Users/rmorin/Zotero/storage/AIIBGXFW/Asmar et al. - 2013 - Genome-wide profiling identifies a DNA methylation.pdf}
}
@article{mentzPARP14NovelTarget2022,
title = {{{PARP14}} Is a Novel Target in {{STAT6}} Mutant Follicular Lymphoma},
author = {Mentz, Michael and Keay, William and Strobl, Carolin Dorothea and Antoniolli, Martina and Adolph, Louisa and Heide, Michael and Lechner, Axel and Haebe, Sarah and Osterode, Elisa and Kridel, Robert and Ziegenhain, Christoph and Wange, Lucas Esteban and Hildebrand, Johannes Adrian and Shree, Tanaya and Silkenstedt, Elisabeth and Staiger, Annette M. and Ott, German and Horn, Heike and Szczepanowski, Monika and Richter, Julia and Levy, Ronald and Rosenwald, Andreas and Enard, Wolfgang and Zimber-Strobl, Ursula and family=Bergwelt-Baildon, given=Michael, prefix=von, useprefix=true and Hiddemann, Wolfgang and Klapper, Wolfram and Schmidt-Supprian, Marc and Rudelius, Martina and Bararia, Deepak and Passerini, Verena and Weigert, Oliver},
date = {2022-09},
journaltitle = {Leukemia},
shortjournal = {Leukemia},
volume = {36},
number = {9},
eprint = {35851155},
eprinttype = {pmid},
pages = {2281--2292},
issn = {1476-5551},
doi = {10.1038/s41375-022-01641-x},
abstract = {The variable clinical course of follicular lymphoma (FL) is determined by the molecular heterogeneity of tumor cells and complex interactions within the tumor microenvironment (TME). IL-4 producing follicular helper T cells (TFH) are critical components of the FL TME. Binding of IL-4 to IL-4R on FL cells activates JAK/STAT signaling. We identified STAT6 mutations (STAT6MUT) in 13\% of FL (N\,=\,33/258), all clustered within the DNA binding domain. Gene expression data and immunohistochemistry showed upregulation of IL-4/STAT6 target genes in STAT6MUT FL, including CCL17, CCL22, and FCER2 (CD23). Functionally, STAT6MUT was gain-of-function by serial replating phenotype in pre-B CFU assays. Expression of STAT6MUT enhanced IL-4 induced FCER2/CD23, CCL17 and CCL22 expression and was associated with nuclear accumulation of pSTAT6. RNA sequencing identified PARP14 -a transcriptional switch and co-activator of STAT6- among the top differentially upregulated genes in IL-4 stimulated STAT6MUT lymphoma cells and in STAT6MUT primary FL cells. Quantitative chromatin immunoprecipitation (qChIP) demonstrated binding of STAT6MUT but not STAT6WT to the PARP14 promotor. Reporter assays showed increased IL-4 induced transactivation activity of STAT6MUT at the PARP14 promotor, suggesting a self-reinforcing regulatory circuit. Knock-down of PARP14 or PARP-inhibition abrogated the STAT6MUT gain-of-function phenotype. Thus, our results identify PARP14 as a novel therapeutic target in STAT6MUT FL.},
langid = {english},
pmcid = {PMC9417990},
keywords = {Humans,Immunohistochemistry,Interleukin-4,Lymphoma B-Cell,Lymphoma Follicular,Poly(ADP-ribose) Polymerases,STAT6 Transcription Factor,Transcriptional Activation,Tumor Microenvironment},
file = {/Users/rmorin/Zotero/storage/YQKA9DY3/Mentz et al. - 2022 - PARP14 is a novel target in STAT6 mutant follicula.pdf}
}
@article{cazzolaBiologicClinicalSignificance2013,
title = {Biologic and Clinical Significance of Somatic Mutations of {{SF3B1}} in Myeloid and Lymphoid Neoplasms},
author = {Cazzola, Mario and Rossi, Marianna and Malcovati, Luca and {Associazione Italiana per la Ricerca sul Cancro Gruppo Italiano Malattie Mieloproliferative}},
date = {2013-01-10},
journaltitle = {Blood},
shortjournal = {Blood},
volume = {121},
number = {2},
eprint = {23160465},
eprinttype = {pmid},
pages = {260--269},
issn = {1528-0020},
doi = {10.1182/blood-2012-09-399725},
abstract = {Precursor mRNA splicing is catalyzed by the spliceosome, a macromolecule composed of small nuclear RNAs associated with proteins. The SF3B1 gene encodes subunit 1 of the splicing factor 3b, which is important for anchoring the spliceosome to precursor mRNA. In 2011, whole-exome sequencing studies showed recurrent somatic mutations of SF3B1 and other genes of the RNA splicing machinery in patients with myelodysplastic syndrome or myelodysplastic/myeloproliferative neoplasm. SF3B1 mutations had a particularly high frequency among conditions characterized by ring sideroblasts, which is consistent with a causal relationship. SF3B1 mutants were also detected at a lower frequency in a variety of other tumor types. In chronic lymphocytic leukemia, SF3B1 was found to be the second most frequently mutated gene. In myelodysplastic syndromes, SF3B1 mutations appear to be founding genetic lesions and are associated with a low risk of leukemic evolution. In contrast, SF3B1 mutations have a lower incidence in early stages of chronic lymphocytic leukemia, are more common in advanced disease, and tend to be associated with poor prognosis, suggesting that they occur during clonal evolution of the disease. The assessment of SF3B1 mutation status may become innovative diagnostic and prognostic tools and the availability of spliceosome modulators opens novel therapeutic prospects.},
langid = {english},
pmcid = {PMC3790951},
keywords = {Humans,Mutation,Myelodysplastic-Myeloproliferative Diseases,Phosphoproteins,Ribonucleoprotein U2 Small Nuclear,RNA Splicing,RNA Splicing Factors},
file = {/Users/rmorin/Zotero/storage/GQCK6NWZ/Cazzola et al. - 2013 - Biologic and clinical significance of somatic muta.pdf}
}
@article{fernandoFunctionalCharacterizationSMARCA42020,
title = {Functional Characterization of {{SMARCA4}} Variants Identified by Targeted Exome-Sequencing of 131,668 Cancer Patients},
author = {Fernando, Tharu M. and Piskol, Robert and Bainer, Russell and Sokol, Ethan S. and Trabucco, Sally E. and Zhang, Qing and Trinh, Huong and Maund, Sophia and Kschonsak, Marc and Chaudhuri, Subhra and Modrusan, Zora and Januario, Thomas and Yauch, Robert L.},
date = {2020-11-03},
journaltitle = {Nature Communications},
shortjournal = {Nat Commun},
volume = {11},
number = {1},
eprint = {33144586},
eprinttype = {pmid},
pages = {5551},
issn = {2041-1723},
doi = {10.1038/s41467-020-19402-8},
abstract = {Genomic studies performed in cancer patients and tumor-derived cell lines have identified a high frequency of alterations in components of the mammalian switch/sucrose non-fermentable (mSWI/SNF or BAF) chromatin remodeling complex, including its core catalytic subunit, SMARCA4. Cells exhibiting loss of SMARCA4 rely on its paralog, SMARCA2, making SMARCA2 an attractive therapeutic target. Here we report the genomic profiling of solid tumors from 131,668 cancer patients, identifying 9434 patients with one or more SMARCA4 gene alterations. Homozygous SMARCA4 mutations were highly prevalent in certain tumor types, notably non-small cell lung cancer (NSCLC), and associated with reduced survival. The large sample size revealed previously uncharacterized hotspot missense mutations within the SMARCA4 helicase domain. Functional characterization of these mutations demonstrated markedly reduced remodeling activity. Surprisingly, a few SMARCA4 missense variants partially or fully rescued paralog dependency, underscoring that careful selection criteria must be employed to identify patients with inactivating, homozygous SMARCA4 missense mutations who may benefit from SMARCA2-targeted therapy.},
langid = {english},
pmcid = {PMC7609548},
keywords = {Carcinogenesis,Cell Line Tumor,Cell Proliferation,Chromatin,Cohort Studies,DNA Helicases,Exome Sequencing,Gene Expression Regulation Neoplastic,Homozygote,Humans,Mutation,Mutation Missense,Neoplasms,Nuclear Proteins,Nucleosomes,Protein Domains,Transcription Factors},
file = {/Users/rmorin/Zotero/storage/B9PHK4HX/Fernando et al. - 2020 - Functional characterization of SMARCA4 variants id.pdf}
}
@article{weberPiggyBacTransposonTools2019,
title = {{{PiggyBac}} Transposon Tools for Recessive Screening Identify {{B-cell}} Lymphoma Drivers in Mice},
author = {Weber, Julia and family=Rosa, given=Jorge, prefix=de la, useprefix=true and Grove, Carolyn S. and Schick, Markus and Rad, Lena and Baranov, Olga and Strong, Alexander and Pfaus, Anja and Friedrich, Mathias J. and Engleitner, Thomas and Lersch, Robert and Öllinger, Rupert and Grau, Michael and Menendez, Irene Gonzalez and Martella, Manuela and Kohlhofer, Ursula and Banerjee, Ruby and Turchaninova, Maria A. and Scherger, Anna and Hoffman, Gary J. and Hess, Julia and Kuhn, Laura B. and Ammon, Tim and Kim, Johnny and Schneider, Günter and Unger, Kristian and Zimber-Strobl, Ursula and Heikenwälder, Mathias and Schmidt-Supprian, Marc and Yang, Fengtang and Saur, Dieter and Liu, Pentao and Steiger, Katja and Chudakov, Dmitriy M. and Lenz, Georg and Quintanilla-Martinez, Leticia and Keller, Ulrich and Vassiliou, George S. and Cadiñanos, Juan and Bradley, Allan and Rad, Roland},
date = {2019-03-29},
journaltitle = {Nature Communications},
shortjournal = {Nat Commun},
volume = {10},
number = {1},
eprint = {30926791},
eprinttype = {pmid},
pages = {1415},
issn = {2041-1723},
doi = {10.1038/s41467-019-09180-3},
abstract = {B-cell lymphoma (BCL) is the most common hematologic malignancy. While sequencing studies gave insights into BCL genetics, identification of non-mutated cancer genes remains challenging. Here, we describe PiggyBac transposon tools and mouse models for recessive screening and show their application to study clonal B-cell lymphomagenesis. In a genome-wide screen, we discover BCL genes related to diverse molecular processes, including signaling, transcriptional regulation, chromatin regulation, or RNA metabolism. Cross-species analyses show the efficiency of the screen to pinpoint human cancer drivers altered by non-genetic mechanisms, including clinically relevant genes dysregulated epigenetically, transcriptionally, or post-transcriptionally in human BCL. We also describe a CRISPR/Cas9-based in vivo platform for BCL functional genomics, and validate discovered genes, such as Rfx7, a transcription factor, and Phip, a chromatin regulator, which suppress lymphomagenesis in mice. Our study gives comprehensive insights into the molecular landscapes of BCL and underlines the power of genome-scale screening to inform biology.},
langid = {english},
pmcid = {PMC6440946},
keywords = {Animals,Clone Cells,CRISPR-Cas Systems,DNA Transposable Elements,Gene Dosage,Gene Expression Regulation Neoplastic,Genes Neoplasm,Genes Tumor Suppressor,Genetic Association Studies,Genetic Testing,Humans,Loss of Heterozygosity,Lymphoma B-Cell,Mice Inbred C57BL,Mice Transgenic,Receptors Antigen B-Cell,Reproducibility of Results},
file = {/Users/rmorin/Zotero/storage/3HPDTVR9/Weber et al. - 2019 - PiggyBac transposon tools for recessive screening .pdf}
}
@article{pinyolInactivationRB1Mantlecell2007,
title = {Inactivation of {{RB1}} in Mantle-Cell Lymphoma Detected by Nonsense-Mediated {{mRNA}} Decay Pathway Inhibition and Microarray Analysis},
author = {Pinyol, Magda and Bea, Silvia and Plà, Laura and Ribrag, Vincent and Bosq, Jacques and Rosenwald, Andreas and Campo, Elias and Jares, Pedro},
date = {2007-06-15},
journaltitle = {Blood},
shortjournal = {Blood},
volume = {109},
number = {12},
eprint = {17332242},
eprinttype = {pmid},
pages = {5422--5429},
issn = {0006-4971},
doi = {10.1182/blood-2006-11-057208},
abstract = {Mantle-cell lymphoma (MCL) is genetically characterized by the translocation t(11;14)(q13;q32) and a high number of secondary chromosomal abnormalities. To identify genes inactivated in this lymphoma, we examined 5 MCL cell lines following a strategy previously described in tumors with microsatellite instability that is based on the combined inhibition of the nonsense-mediated mRNA decay pathway and gene-expression profiling. This approach, together with the design of a conservative algorithm for analysis of the results, allowed the identification of 3 genes carrying premature stop codons. These genes were p53 with a mutation previously described in JEKO-1, the leukocyte-derived arginine aminopeptidase (LRAP) gene in REC-1 that showed a new splicing isoform generating a premature stop codon, and RB1 in UPN-1 that contained an intragenic homozygous deletion resulting in a truncated transcript and total loss of protein expression. The new LRAP isoform was detected also in 2 primary MCLs, whereas inactivating intragenic deletions of RB1 were found in the primary tumor from which UPN-1 was derived and 1 additional blastoid MCL. These tumors carried a concomitant inactivation of p53, whereas p16INK4a was wild type. These results indicate for the first time that RB1 may be inactivated in aggressive MCL by intragenic deletions.},
langid = {english},
keywords = {Algorithms,Cell Line Tumor,Codon Nonsense,Dental Enamel Proteins,Gene Expression Profiling,Gene Silencing,Humans,Lymphoma Mantle-Cell,Microarray Analysis,Protein Isoforms,Retinoblastoma Protein,RNA Messenger,Tumor Suppressor Protein p53},
file = {/Users/rmorin/Zotero/storage/AVNQXD5P/Pinyol et al. - 2007 - Inactivation of RB1 in mantle-cell lymphoma detect.pdf}
}
@article{freieGermlinePointMutation2024,
title = {A Germline Point Mutation in the {{MYC-FBW7}} Phosphodegron Initiates Hematopoietic Malignancies},
author = {Freie, Brian and Carroll, Patrick A. and Varnum-Finney, Barbara J. and Ramsey, Erin L. and Ramani, Vijay and Bernstein, Irwin and Eisenman, Robert N.},
date = {2024-04-17},
journaltitle = {Genes \& Development},
shortjournal = {Genes Dev},
volume = {38},
number = {5-6},
eprint = {38565249},
eprinttype = {pmid},
pages = {253--272},
issn = {1549-5477},
doi = {10.1101/gad.351292.123},
abstract = {Oncogenic activation of MYC in cancers predominantly involves increased transcription rather than coding region mutations. However, MYC-dependent lymphomas frequently acquire point mutations in the MYC phosphodegron, including at threonine 58 (T58), where phosphorylation permits binding via the FBW7 ubiquitin ligase triggering MYC degradation. To understand how T58 phosphorylation functions in normal cell physiology, we introduced an alanine mutation at T58 (T58A) into the endogenous c-Myc locus in the mouse germline. While MYC-T58A mice develop normally, lymphomas and myeloid leukemias emerge in ∼60\% of adult homozygous T58A mice. We found that primitive hematopoietic progenitor cells from MYC-T58A mice exhibit aberrant self-renewal normally associated with hematopoietic stem cells (HSCs) and up-regulate a subset of MYC target genes important in maintaining stem/progenitor cell balance. In lymphocytes, genomic occupancy by MYC-T58A was increased at all promoters compared with WT MYC, while genes differentially expressed in a T58A-dependent manner were significantly more proximal to MYC-bound enhancers. MYC-T58A lymphocyte progenitors exhibited metabolic alterations and decreased activation of inflammatory and apoptotic pathways. Our data demonstrate that a single point mutation stabilizing MYC is sufficient to skew target gene expression, producing a profound gain of function in multipotential hematopoietic progenitors associated with self-renewal and initiation of lymphomas and leukemias.},
langid = {english},
pmcid = {PMC11065175},
keywords = {Animals,F-Box-WD Repeat-Containing Protein 7,FBW7,Germ Cells,Hematologic Neoplasms,hematopoiesis,Hematopoietic Stem Cells,leukemia,lymphoma,Lymphoma,Mice,MYC,Point Mutation,progenitor cells,protein stability,Proto-Oncogene Proteins c-myc,self-renewal},
file = {/Users/rmorin/Zotero/storage/5ZEIGWRU/Freie et al. - 2024 - A germline point mutation in the MYC-FBW7 phosphod.pdf}
}
@article{demosthenousLossFunctionMutations2015,
title = {Loss of Function Mutations in {{PTPN6}} Promote {{STAT3}} Deregulation via {{JAK3}} Kinase in Diffuse Large {{B-cell}} Lymphoma},
author = {Demosthenous, Christos and Han, Jing Jing and Hu, Guangzhen and Stenson, Mary and Gupta, Mamta},
date = {2015-12-29},
journaltitle = {Oncotarget},
shortjournal = {Oncotarget},
volume = {6},
number = {42},
eprint = {26565811},
eprinttype = {pmid},
pages = {44703--44713},
issn = {1949-2553},
doi = {10.18632/oncotarget.6300},
abstract = {PTPN6 (SHP1) is a tyrosine phosphatase that negatively controls the activity of multiple signaling pathways including STAT signaling, however role of mutated PTPN6 is not much known. Here we investigated whether PTPN6 might also be a potential target for diffuse large B cell lymphoma (DLBCL) and performed Sanger sequencing of the PTPN6 gene. We have identified missense mutations within PTPN6 (N225K and A550V) in 5\% (2/38) of DLBCL tumors. Site directed mutagenesis was performed to mutate wild type (WT) PTPN6 and stable cell lines were generated by lentiviral transduction of PTPN6(WT), PTPN6(N225K) and PTPN6(A550V) constructs, and effects of WT or mutated PTPN6 on STAT3 signaling were analyzed. WT PTPN6 dephosphorylated STAT3, but had no effect on STAT1, STAT5 or STAT6 phosphorylation. Both PTPN6 mutants were unable to inhibit constitutive, as well as cytokines induced STAT3 activation. Both PTPN6 mutants also demonstrated reduced tyrosine phosphatase activity and exhibited enhanced STAT3 transactivation activity. Intriguingly, a lack of direct binding between STAT3 and WT or mutated PTPN6 was observed. However, compared to WT PTPN6, cells expressing PTPN6 mutants exhibited increased binding between JAK3 and PTPN6 suggesting a more dynamic interaction of PTPN6 with upstream regulators of STAT3. Consistent with this notion, both the mutants demonstrated increased resistance to JAK3 inhibitor, WHIP-154 relative to WT PTPN6. Overall, this is the first study, which demonstrates that N225K and A550V PTPN6 mutations cause loss-of-function leading to JAK3 mediated deregulation of STAT3 pathway and uncovers a mechanism that tumor cells can use to control PTPN6 substrate specificity.},
langid = {english},
pmcid = {PMC4792586},
keywords = {Antineoplastic Agents,DLBCL,Drug Resistance Neoplasm,Gene Expression Regulation Enzymologic,Gene Expression Regulation Neoplastic,HEK293 Cells,Humans,JAK kinases,Janus Kinase 3,Lymphoma Large B-Cell Diffuse,Mutagenesis Site-Directed,Mutation Missense,Phosphorylation,Protein Binding,Protein Kinase Inhibitors,Protein Tyrosine Phosphatase Non-Receptor Type 6,PTPN6 mutations,Signal Transduction,STAT3,STAT3 Transcription Factor,Substrate Specificity,Transfection},
file = {/Users/rmorin/Zotero/storage/3T2BAVY4/Demosthenous et al. - 2015 - Loss of function mutations in PTPN6 promote STAT3 .pdf}
}
@article{grabinerDiverseArrayCancerassociated2014,
title = {A Diverse Array of Cancer-Associated {{MTOR}} Mutations Are Hyperactivating and Can Predict Rapamycin Sensitivity},
author = {Grabiner, Brian C. and Nardi, Valentina and Birsoy, Kıvanc and Possemato, Richard and Shen, Kuang and Sinha, Sumi and Jordan, Alexander and Beck, Andrew H. and Sabatini, David M.},
date = {2014-05},
journaltitle = {Cancer Discovery},
shortjournal = {Cancer Discov},
volume = {4},
number = {5},
eprint = {24631838},
eprinttype = {pmid},
pages = {554--563},
issn = {2159-8290},
doi = {10.1158/2159-8290.CD-13-0929},
abstract = {Genes encoding components of the PI3K-AKT-mTOR signaling axis are frequently mutated in cancer, but few mutations have been characterized in MTOR, the gene encoding the mTOR kinase. Using publicly available tumor genome sequencing data, we generated a comprehensive catalog of mTOR pathway mutations in cancer, identifying 33 MTOR mutations that confer pathway hyperactivation. The mutations cluster in six distinct regions in the C-terminal half of mTOR and occur in multiple cancer types, with one cluster particularly prominent in kidney cancer. The activating mutations do not affect mTOR complex assembly, but a subset reduces binding to the mTOR inhibitor DEPTOR. mTOR complex 1 (mTORC1) signaling in cells expressing various activating mutations remains sensitive to pharmacologic mTOR inhibition, but is partially resistant to nutrient deprivation. Finally, cancer cell lines with hyperactivating MTOR mutations display heightened sensitivity to rapamycin both in culture and in vivo xenografts, suggesting that such mutations confer mTOR pathway dependency.},
langid = {english},
pmcid = {PMC4012430},
keywords = {Animals,Antibiotics Antineoplastic,Cell Line Tumor,Databases Factual,HEK293 Cells,HeLa Cells,Humans,MAP Kinase Signaling System,MCF-7 Cells,Mechanistic Target of Rapamycin Complex 1,Mechanistic Target of Rapamycin Complex 2,Mice,Mice Nude,Multiprotein Complexes,Mutation,Neoplasms,Neoplasms Experimental,Protein Kinase Inhibitors,Sirolimus,TOR Serine-Threonine Kinases,Xenograft Model Antitumor Assays},
file = {/Users/rmorin/Zotero/storage/9XHKLA8X/Grabiner et al. - 2014 - A diverse array of cancer-associated MTOR mutation.pdf}
}
@article{trissalMIR142LossofFunctionMutations2018,
title = {{{MIR142 Loss-of-Function Mutations Derepress ASH1L}} to {{Increase HOXA Gene Expression}} and {{Promote Leukemogenesis}}},
author = {Trissal, Maria C. and Wong, Terrence N. and Yao, Juo-Chin and Ramaswamy, Rahul and Kuo, Iris and Baty, Jack and Sun, Yaping and Jih, Gloria and Parikh, Nishi and Berrien-Elliott, Melissa M. and Fehniger, Todd A. and Ley, Timothy J. and Maillard, Ivan and Reddy, Pavan R. and Link, Daniel C.},
date = {2018-07-01},
journaltitle = {Cancer Research},
shortjournal = {Cancer Res},
volume = {78},
number = {13},
eprint = {29724719},
eprinttype = {pmid},
pages = {3510--3521},
issn = {1538-7445},
doi = {10.1158/0008-5472.CAN-17-3592},
abstract = {Point mutations in the seed sequence of miR-142-3p are present in a subset of acute myelogenous leukemia (AML) and in several subtypes of B-cell lymphoma. Here, we show that mutations associated with AML result both in loss of miR-142-3p function and in decreased miR-142-5p expression. Mir142 loss altered the hematopoietic differentiation of multipotent hematopoietic progenitors, enhancing their myeloid potential while suppressing their lymphoid potential. During hematopoietic maturation, loss of Mir142 increased ASH1L protein expression and consequently resulted in the aberrant maintenance of Hoxa gene expression in myeloid-committed hematopoietic progenitors. Mir142 loss also enhanced the disease-initiating activity of IDH2-mutant hematopoietic cells in mice. Together these data suggest a novel model in which miR-142, through repression of ASH1L activity, plays a key role in suppressing HOXA9/A10 expression during normal myeloid differentiation. AML-associated loss-of-function mutations of MIR142 disrupt this negative signaling pathway, resulting in sustained HOXA9/A10 expression in myeloid progenitors/myeloblasts and ultimately contributing to leukemic transformation.Significance: These findings provide mechanistic insights into the role of miRNAs in leukemogenesis and hematopoietic stem cell function. Cancer Res; 78(13); 3510-21. ©2018 AACR.},
langid = {english},
pmcid = {PMC6030481},
keywords = {Animals,Bone Marrow,Carcinogenesis,Disease Models Animal,DNA-Binding Proteins,Gene Expression Regulation Leukemic,HEK293 Cells,Hematopoietic Stem Cells,Histone-Lysine N-Methyltransferase,Homeobox A10 Proteins,Homeodomain Proteins,Humans,Isocitrate Dehydrogenase,Leukemia Myeloid Acute,Loss of Function Mutation,Mice,Mice Inbred C57BL,Mice Knockout,MicroRNAs,Point Mutation,Receptor EphB2,Signal Transduction,Transcription Factors},
file = {/Users/rmorin/Zotero/storage/IZCJQVV3/Trissal et al. - 2018 - MIR142 Loss-of-Function Mutations Derepress ASH1L .pdf}
}
@article{depaoliMGASuppressorMYC2013,
title = {{{MGA}}, a Suppressor of {{MYC}}, Is Recurrently Inactivated in High Risk Chronic Lymphocytic Leukemia},
author = {De Paoli, Lorenzo and Cerri, Michaela and Monti, Sara and Rasi, Silvia and Spina, Valeria and Bruscaggin, Alessio and Greco, Mariangela and Ciardullo, Carmela and Famà, Rosella and Cresta, Stefania and Maffei, Rossana and Ladetto, Marco and Martini, Maurizio and Laurenti, Luca and Forconi, Francesco and Marasca, Roberto and Larocca, Luigi M. and Bertoni, Francesco and Gaidano, Gianluca and Rossi, Davide},
date = {2013-05},
journaltitle = {Leukemia \& Lymphoma},
shortjournal = {Leuk Lymphoma},
volume = {54},
number = {5},
eprint = {23039309},
eprinttype = {pmid},
pages = {1087--1090},
issn = {1029-2403},
doi = {10.3109/10428194.2012.723706},
langid = {english},
keywords = {Base Sequence,Basic Helix-Loop-Helix Transcription Factors,Gene Deletion,Humans,Leukemia Lymphocytic Chronic B-Cell,Mutation,Proto-Oncogene Proteins c-myc}
}
@article{scheffzekRasRasGAPComplexStructural1997,
title = {The {{Ras-RasGAP}} Complex: Structural Basis for {{GTPase}} Activation and Its Loss in Oncogenic {{Ras}} Mutants},
shorttitle = {The {{Ras-RasGAP}} Complex},
author = {Scheffzek, K. and Ahmadian, M. R. and Kabsch, W. and Wiesmüller, L. and Lautwein, A. and Schmitz, F. and Wittinghofer, A.},
date = {1997-07-18},
journaltitle = {Science (New York, N.Y.)},
shortjournal = {Science},
volume = {277},
number = {5324},
eprint = {9219684},
eprinttype = {pmid},
pages = {333--338},
issn = {0036-8075},
doi = {10.1126/science.277.5324.333},
abstract = {The three-dimensional structure of the complex between human H-Ras bound to guanosine diphosphate and the guanosine triphosphatase (GTPase)-activating domain of the human GTPase-activating protein p120GAP (GAP-334) in the presence of aluminum fluoride was solved at a resolution of 2.5 angstroms. The structure shows the partly hydrophilic and partly hydrophobic nature of the communication between the two molecules, which explains the sensitivity of the interaction toward both salts and lipids. An arginine side chain (arginine-789) of GAP-334 is supplied into the active site of Ras to neutralize developing charges in the transition state. The switch II region of Ras is stabilized by GAP-334, thus allowing glutamine-61 of Ras, mutation of which activates the oncogenic potential, to participate in catalysis. The structural arrangement in the active site is consistent with a mostly associative mechanism of phosphoryl transfer and provides an explanation for the activation of Ras by glycine-12 and glutamine-61 mutations. Glycine-12 in the transition state mimic is within van der Waals distance of both arginine-789 of GAP-334 and glutamine-61 of Ras, and even its mutation to alanine would disturb the arrangements of residues in the transition state.},
langid = {english},
keywords = {Aluminum Compounds,Amino Acid Sequence,Binding Sites,Catalysis,Cell Transformation Neoplastic,Crystallography X-Ray,Enzyme Activation,Fluorides,GTP Phosphohydrolases,GTP-Binding Proteins,GTPase-Activating Proteins,Guanosine Diphosphate,Guanosine Triphosphate,Humans,Models Molecular,Molecular Sequence Data,Mutation,Protein Conformation,Protein Structure Secondary,Proteins,ras GTPase-Activating Proteins,ras Proteins,Signal Transduction}
}
@article{pfeiferPTENLossDefines2013,
title = {{{PTEN}} Loss Defines a {{PI3K}}/{{AKT}} Pathway-Dependent Germinal Center Subtype of Diffuse Large {{B-cell}} Lymphoma},
author = {Pfeifer, Matthias and Grau, Michael and Lenze, Dido and Wenzel, Sören-Sebastian and Wolf, Annette and Wollert-Wulf, Brigitte and Dietze, Kerstin and Nogai, Hendrik and Storek, Benjamin and Madle, Hannelore and Dörken, Bernd and Janz, Martin and Dirnhofer, Stephan and Lenz, Peter and Hummel, Michael and Tzankov, Alexandar and Lenz, Georg},
date = {2013-07-23},
journaltitle = {Proceedings of the National Academy of Sciences of the United States of America},
shortjournal = {Proc Natl Acad Sci U S A},
volume = {110},
number = {30},
eprint = {23840064},
eprinttype = {pmid},
pages = {12420--12425},
issn = {1091-6490},
doi = {10.1073/pnas.1305656110},
abstract = {Diffuse large B-cell lymphoma (DLBCL) represents a heterogeneous diagnostic category with distinct molecular subtypes that can be defined by gene expression profiling. However, even within these defined subtypes, heterogeneity prevails. To further elucidate the pathogenesis of these entities, we determined the expression of the tumor suppressor phosphatase and tensin homolog (PTEN) in 248 primary DLBCL patient samples. These analyses revealed that loss of PTEN was detectable in 55\% of germinal center B-cell-like (GCB) DLBCLs, whereas this abnormality was found in only 14\% of non-GCB DLBCL patient samples. In GCB DLBCL, the PTEN status was inversely correlated with activation of the oncogenic PI3K/protein kinase B (AKT) pathway in both DLBCL cell lines and primary patient samples. Reexpression of PTEN induced cytotoxicity in PTEN-deficient GCB DLBCL cell line models by inhibiting PI3K/AKT signaling, indicating an addiction to this pathway in this subset of GCB DLBCLs. PI3K/AKT inhibition induced down-regulation of the transcription factor MYC. Reexpression of MYC rescued GCB DLBCL cells from PTEN-induced toxicity, identifying a regulatory mechanism of MYC expression in DLBCL. Finally, pharmacologic PI3K inhibition resulted in toxicity selectively in PTEN-deficient GCB DLBCL lines. Collectively, our results indicate that PTEN loss defines a PI3K/AKT-dependent GCB DLBCL subtype that is addicted to PI3K and MYC signaling and suggest that pharmacologic inhibition of PI3K might represent a promising therapeutic approach in these lymphomas.},
langid = {english},
pmcid = {PMC3725065},
keywords = {Cohort Studies,Humans,Lymphoma Large B-Cell Diffuse,lymphopedia,p38 Mitogen-Activated Protein Kinases,Phosphatidylinositol 3-Kinases,PTEN Phosphohydrolase,Signal Transduction},
file = {/Users/rmorin/Zotero/storage/XALB6YM6/Pfeifer et al. - 2013 - PTEN loss defines a PI3KAKT pathway-dependent ger.pdf}
}
@article{hodsonRegulationNormalBcell2016,
title = {Regulation of Normal {{B-cell}} Differentiation and Malignant {{B-cell}} Survival by {{OCT2}}},
author = {Hodson, Daniel J. and Shaffer, Arthur L. and Xiao, Wenming and Wright, George W. and Schmitz, Roland and Phelan, James D. and Yang, Yandan and Webster, Daniel E. and Rui, Lixin and Kohlhammer, Holger and Nakagawa, Masao and Waldmann, Thomas A. and Staudt, Louis M.},
date = {2016-04-05},
journaltitle = {Proceedings of the National Academy of Sciences of the United States of America},
shortjournal = {Proc Natl Acad Sci U S A},
volume = {113},
number = {14},
eprint = {26993806},
eprinttype = {pmid},
pages = {E2039-2046},
issn = {1091-6490},
doi = {10.1073/pnas.1600557113},
abstract = {The requirement for the B-cell transcription factor OCT2 (octamer-binding protein 2, encoded by Pou2f2) in germinal center B cells has proved controversial. Here, we report that germinal center B cells are formed normally after depletion of OCT2 in a conditional knockout mouse, but their proliferation is reduced and in vivo differentiation to antibody-secreting plasma cells is blocked. This finding led us to examine the role of OCT2 in germinal center-derived lymphomas. shRNA knockdown showed that almost all diffuse large B-cell lymphoma (DLBCL) cell lines are addicted to the expression of OCT2 and its coactivator OCA-B. Genome-wide chromatin immunoprecipitation (ChIP) analysis and gene-expression profiling revealed the broad transcriptional program regulated by OCT2 that includes the expression of STAT3, IL-10, ELL2, XBP1, MYC, TERT, and ADA. Importantly, genetic alteration of OCT2 is not a requirement for cellular addiction in DLBCL. However, we detected amplifications of the POU2F2 locus in DLBCL tumor biopsies and a recurrent mutation of threonine 223 in the DNA-binding domain of OCT2. This neomorphic mutation subtly alters the DNA-binding preference of OCT2, leading to the transactivation of noncanonical target genes including HIF1a and FCRL3 Finally, by introducing mutations designed to disrupt the OCT2-OCA-B interface, we reveal a requirement for this protein-protein interface that ultimately might be exploited therapeutically. Our findings, combined with the predominantly B-cell-restricted expression of OCT2 and the absence of a systemic phenotype in our knockout mice, suggest that an OCT2-targeted therapeutic strategy would be efficacious in both major subtypes of DLBCL while avoiding systemic toxicity.},
langid = {english},
pmcid = {PMC4833274},
keywords = {Animals,B-Lymphocytes,cancer biology,Cell Differentiation,Cell Line Tumor,Cell Survival,germinal center,lymphoma,Lymphoma Large B-Cell Diffuse,lymphopedia,Mice,Mice Knockout,Organic Cation Transport Proteins,Organic Cation Transporter 2},
file = {/Users/rmorin/Zotero/storage/IMDHB5EC/Hodson et al. - 2016 - Regulation of normal B-cell differentiation and ma.pdf;/Users/rmorin/Zotero/storage/YQRVND4V/Hodson et al. - 2016 - Regulation of normal B-cell differentiation and ma.pdf}
}
@article{gaoSGK1MutationsDLBCL2021,
title = {{{SGK1}} Mutations in {{DLBCL}} Generate Hyperstable Protein Neoisoforms That Promote {{AKT}} Independence},
author = {Gao, Jie and Sidiropoulou, Eirini and Walker, Ieuan and Krupka, Joanna A. and Mizielinski, Karol and Usheva, Zelvera and Samarajiwa, Shamith A. and Hodson, Daniel J.},
date = {2021-09-16},
journaltitle = {Blood},
shortjournal = {Blood},
volume = {138},
number = {11},
eprint = {33988691},
eprinttype = {pmid},
pages = {959--964},
issn = {1528-0020},
doi = {10.1182/blood.2020010432},
abstract = {Serum and glucocorticoid-regulated kinase 1 (SGK1) is one of the most frequently mutated genes in diffuse large B-cell lymphoma (DLBCL). However, little is known about its function or the consequence of its mutation. The frequent finding of truncating mutations has led to the widespread assumption that these represent loss-of-function variants and, accordingly, that SGK1 must act as a tumor suppressor. In this study, instead, the most common SGK1 mutations led to production of aberrantly spliced messenger RNA neoisoforms in which translation is initiated from downstream methionines. The resulting N-terminal truncated protein isoforms showed increased expression related to the exclusion of an N-terminal degradation domain. However, they retained a functional kinase domain, the overexpression of which rendered cells resistant to AKT inhibition, in part because of increased phosphorylation of GSK3B. These findings challenge the prevailing assumption that SGK1 is a tumor-suppressor gene in DLBCL and provide the impetus to explore further the pharmacological inhibition of SGK1 as a therapeutic strategy for DLBCL.},
langid = {english},
pmcid = {PMC8701626},
keywords = {Cells Cultured,Enzyme Stability,Humans,Immediate-Early Proteins,Lymphoma Large B-Cell Diffuse,lymphopedia,Phosphorylation,Protein Domains,Protein Isoforms,Protein Serine-Threonine Kinases,Proto-Oncogene Proteins c-akt},
file = {/Users/rmorin/Zotero/storage/J9ETHUL6/Gao et al. - 2021 - SGK1 mutations in DLBCL generate hyperstable prote.pdf;/Users/rmorin/Zotero/storage/TXGZRW9Y/Gao et al. - 2021 - SGK1 mutations in DLBCL generate hyperstable prote.pdf}
}
@article{gonzalez-rinconUnravelingTransformationFollicular2019,
title = {Unraveling Transformation of Follicular Lymphoma to Diffuse Large {{B-cell}} Lymphoma},
author = {González-Rincón, Julia and Méndez, Miriam and Gómez, Sagrario and García, Juan F. and Martín, Paloma and Bellas, Carmen and Pedrosa, Lucía and Rodríguez-Pinilla, Socorro M. and Camacho, Francisca I. and Quero, Cristina and Pérez-Callejo, David and Rueda, Antonio and Llanos, Marta and Gómez-Codina, José and Piris, Miguel A. and Montes-Moreno, Santiago and Bárcena, Carmen and Rodríguez-Abreu, Delvys and Menárguez, Javier and family=Cruz-Merino, given=Luis, prefix=de la, useprefix=true and Monsalvo, Silvia and Parejo, Consuelo and Royuela, Ana and Kwee, Ivo and Cascione, Luciano and Arribas, Alberto and Bertoni, Francesco and Mollejo, Manuela and Provencio, Mariano and Sánchez-Beato, Margarita},
date = {2019},
journaltitle = {PloS One},
shortjournal = {PLoS One},
volume = {14},
number = {2},
eprint = {30802265},
eprinttype = {pmid},
pages = {e0212813},
issn = {1932-6203},
doi = {10.1371/journal.pone.0212813},
abstract = {Follicular lymphoma (FL) is an indolent but largely incurable disease. Some patients suffer histological transformation to a more aggressive subtype with poorer prognosis. This study aimed to improve our understanding of the genetics underlying FL histological transformation, and to identify genetic drivers or promoters of the transformation by elucidating the differences between FL samples from patients who did and did not transform. We conducted targeted massive parallel sequencing of 22 pre-transformed FL/transformed diffuse large B-cell lymphoma pairs and 20 diagnostic samples from non-transformed FL patients. Additionally, 22 matched samples from 11 transformed FL patients (pre-transformed FL and diffuse large B-cell lymphoma) and 9 non-transformed FLs were studied for copy number variation using SNP arrays. We identified recurrently mutated genes that were enriched at transformation, most notably LRP1B, GNA13 and POU2AF1, which have roles in B-cell differentiation, GC architecture and migration. Mutations in POU2AF1 might be associated with lower levels of expression, were more frequent in transformed FLs, and seemed to be specific to transformed- compared with de novo-diffuse large B-cell lymphomas. Pre-transformed FLs carried more mutations per sample and had greater subclonal heterogeneity than non-transformed FLs. Finally, we identified four mutated genes in FL samples that differed between patients who did and did not transform: NOTCH2, DTX1, UBE2A and HIST1H1E. The presence of mutations in these genes was associated with shorter time to transformation when mutated in the FL biopsies. This information might be useful for identifying patients at higher risk of transformation.},
langid = {english},
pmcid = {PMC6388933},
keywords = {Adult,Aged,B-Lymphocytes,Biopsy,Cell Differentiation,Cell Transformation Neoplastic,Female,Follow-Up Studies,Humans,Lymphoma Follicular,Lymphoma Large B-Cell Diffuse,Male,Middle Aged,Mutation,Neoplasm Proteins},
file = {/Users/rmorin/Zotero/storage/BBLFASN6/González-Rincón et al. - 2019 - Unraveling transformation of follicular lymphoma t.pdf}
}
@article{jungnickelClonalDeleteriousMutations2000,
title = {Clonal Deleterious Mutations in the {{IkappaBalpha}} Gene in the Malignant Cells in {{Hodgkin}}'s Lymphoma},
author = {Jungnickel, B. and Staratschek-Jox, A. and Bräuninger, A. and Spieker, T. and Wolf, J. and Diehl, V. and Hansmann, M. L. and Rajewsky, K. and Küppers, R.},
date = {2000-01-17},
journaltitle = {The Journal of Experimental Medicine},
shortjournal = {J Exp Med},
volume = {191},
number = {2},
eprint = {10637284},
eprinttype = {pmid},
pages = {395--402},
issn = {0022-1007},
doi = {10.1084/jem.191.2.395},
abstract = {Members of the nuclear factor (NF)-kappaB family of transcription factors play a crucial role in cellular activation, immune responses, and oncogenesis. In most cells, they are kept inactive in the cytosol by complex formation with members of the inhibitor of NF-kappaB (IkappaB) family, whose degradation activates NF-kappaB in response to diverse stimuli. In Hodgkin's lymphoma (HL), high constitutive nuclear activity of NF-kappaB is characteristic of the malignant Hodgkin and Reed-Sternberg (H/RS) cells, which occur at low number in a background of nonneoplastic inflammatory cells. In single H/RS cells micromanipulated from histological sections of HL, we detect clonal deleterious somatic mutations in the IkappaBalpha gene in two of three Epstein-Barr virus (EBV)-negative cases but not in two EBV-positive cases (in which a viral oncogene may account for NF-kappaB activation). There was no evidence for IkappaBalpha mutations in two non-HL entities or in normal germinal center B cells. This study establishes deleterious IkappaBalpha mutations as the first recurrent genetic defect found in H/RS cells, indicating a role of IkappaBalpha defects in the pathogenesis of HL and implying that IkappaBalpha is a tumor suppressor gene.},
langid = {english},
pmcid = {PMC2195754},
keywords = {Adult,Child,DNA-Binding Proteins,Female,Gene Deletion,Hodgkin Disease,Humans,I-kappa B Proteins,Male,NF-KappaB Inhibitor alpha,Tumor Cells Cultured},
file = {/Users/rmorin/Zotero/storage/CABELY4P/Jungnickel et al. - 2000 - Clonal deleterious mutations in the IkappaBalpha g.pdf}
}
@article{kuoRolePIM1Ibrutinibresistant2016,
title = {The Role of {{PIM1}} in the Ibrutinib-Resistant {{ABC}} Subtype of Diffuse Large {{B-cell}} Lymphoma},
author = {Kuo, Hsu-Ping and Ezell, Scott A. and Hsieh, Sidney and Schweighofer, Karl J. and Cheung, Leo Wk and Wu, Shiquan and Apatira, Mutiah and Sirisawad, Mint and Eckert, Karl and Liang, Yu and Hsu, Jeff and Chen, Chun-Te and Beaupre, Darrin and Chang, Betty Y.},
date = {2016},
journaltitle = {American Journal of Cancer Research},
shortjournal = {Am J Cancer Res},
volume = {6},
number = {11},
eprint = {27904766},
eprinttype = {pmid},
pages = {2489--2501},
issn = {2156-6976},
abstract = {Diffuse large B cell lymphoma (DLBCL) is a heterogeneous lymphoma and the most common subtype of non-Hodgkin lymphoma, accounting for roughly 30\% of newly diagnosed cases in the United States. DLBCL can be separated into the activated B cell-like (ABC) and germinal center B cell-like (GCB) subtypes, with distinct gene expression profiles, oncogenic aberrations, and clinical outcomes. ABC-DLBCL is characterized by chronically active B-cell receptor (BCR) signaling that can be modulated by Bruton's tyrosine kinase (BTK) activity. Thus, BTK serves as an attractive therapeutic target in this type of B-cell malignancy. Ibrutinib, a first-in-class, orally available covalent BTK inhibitor, has demonstrated clinical activity in several B-cell leukemias and lymphomas. A phase 1/2 clinical trial of single-agent ibrutinib in relapsed and refractory DLBCL patients revealed an overall response rate of 37\% in ABC-DLBCL patients. However, responses to kinase-directed therapies are often limited by emerging resistance mechanisms that bypass the therapeutic target. Here we report the discovery of point mutations within the kinase PIM1 that reduce sensitivity to ibrutinib in ABC-DLBCL. These mutations stabilize PIM1 and affect upstream regulators and downstream targets of NF-κB signaling. The introduction of mutant PIM1 into an ABC-DLBCL cell line, TMD8, increased colony formation and decreased sensitivity to ibrutinib. In addition, ibrutinib-resistant cell lines generated by prolonged ibrutinib exposure in vitro upregulated PIM1 expression, consistent with a role for PIM1 in antagonizing ibrutinib activity. The combination of a pan-PIM inhibitor with ibrutinib synergistically inhibited proliferation in vitro and tumor growth in vivo. Together, these data provide a rationale for combining BTK and PIM1 inhibition in the treatment of ABC-DLBCL.},
langid = {english},
pmcid = {PMC5126268},
keywords = {Bruton’s tyrosine kinase,DLBCL,ibrutinib,PIM1}
}
@article{ryanCellRegulomeLinks2017,
title = {A {{B Cell Regulome Links Notch}} to {{Downstream Oncogenic Pathways}} in {{Small B Cell Lymphomas}}},
author = {Ryan, Russell J. H. and Petrovic, Jelena and Rausch, Dylan M. and Zhou, Yeqiao and Lareau, Caleb A. and Kluk, Michael J. and Christie, Amanda L. and Lee, Winston Y. and Tarjan, Daniel R. and Guo, Bingqian and Donohue, Laura K. H. and Gillespie, Shawn M. and Nardi, Valentina and Hochberg, Ephraim P. and Blacklow, Stephen C. and Weinstock, David M. and Faryabi, Robert B. and Bernstein, Bradley E. and Aster, Jon C. and Pear, Warren S.},
date = {2017-10-17},
journaltitle = {Cell Reports},
shortjournal = {Cell Rep},
volume = {21},
number = {3},
eprint = {29045844},
eprinttype = {pmid},
pages = {784--797},
issn = {2211-1247},
doi = {10.1016/j.celrep.2017.09.066},
abstract = {Gain-of-function Notch mutations are recurrent in mature small B cell lymphomas such as mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL), but the Notch target genes that contribute to B cell oncogenesis are largely unknown. We performed integrative analysis of Notch-regulated transcripts, genomic binding of Notch transcription complexes, and genome conformation data to identify direct Notch target genes in MCL cell lines. This B~cell Notch regulome is largely controlled through Notch-bound distal enhancers and includes genes involved in B cell receptor and cytokine signaling and the oncogene MYC, which sustains proliferation of Notch-dependent MCL cell lines via a Notch-regulated lineage-restricted enhancer complex. Expression of direct Notch target genes is associated with Notch activity in an MCL xenograft model and in CLL lymph node biopsies. Our findings provide key insights into the role of Notch in MCL and other B~cell malignancies and have important implications for therapeutic targeting of Notch-dependent oncogenic pathways.},
langid = {english},
pmcid = {PMC5687286},
keywords = {Animals,B-Lymphocytes,Biopsy,Cell Differentiation,Cell Line Tumor,chronic lymphocytic leukemia,Enhancer Elements Genetic,Gene Expression Regulation Neoplastic,Gene Rearrangement,Humans,Lymph Nodes,lymphoma,Lymphoma B-Cell,mantle cell lymphoma,Mice,MYC,Notch signaling,Oncogenes,Proto-Oncogene Proteins c-myc,Receptors Notch,Signal Transduction,Tumor Microenvironment,Xenograft Model Antitumor Assays},
file = {/Users/rmorin/Zotero/storage/THJV7L2D/Ryan et al. - 2017 - A B Cell Regulome Links Notch to Downstream Oncoge.pdf}
}
@article{lazarianHotspotMutationTranscription2021,
title = {A Hotspot Mutation in Transcription Factor {{IKZF3}} Drives {{B}} Cell Neoplasia via Transcriptional Dysregulation},
author = {Lazarian, Gregory and Yin, Shanye and Ten Hacken, Elisa and Sewastianik, Tomasz and Uduman, Mohamed and Font-Tello, Alba and Gohil, Satyen H. and Li, Shuqiang and Kim, Ekaterina and Joyal, Heather and Billington, Leah and Witten, Elizabeth and Zheng, Mei and Huang, Teddy and Severgnini, Mariano and Lefebvre, Valerie and Rassenti, Laura Z. and Gutierrez, Catherine and Georgopoulos, Katia and Ott, Christopher J. and Wang, Lili and Kipps, Thomas J. and Burger, Jan A. and Livak, Kenneth J. and Neuberg, Donna S. and Baran-Marszak, Fanny and Cymbalista, Florence and Carrasco, Ruben D. and Wu, Catherine J.},
date = {2021-03-08},
journaltitle = {Cancer Cell},
shortjournal = {Cancer Cell},
volume = {39},
number = {3},
eprint = {33689703},
eprinttype = {pmid},
pages = {380-393.e8},
issn = {1878-3686},
doi = {10.1016/j.ccell.2021.02.003},
abstract = {Hotspot mutation of IKZF3 (IKZF3-L162R) has been identified as a putative driver of chronic lymphocytic leukemia (CLL), but its function remains unknown. Here, we demonstrate its driving role in CLL through a B cell-restricted conditional knockin mouse model. Mutant Ikzf3 alters DNA binding specificity and target selection, leading to hyperactivation of B cell receptor (BCR) signaling, overexpression of nuclear factor κB (NF-κB) target genes, and development of CLL-like disease in elderly mice with a penetrance of \textasciitilde 40\%. Human CLL carrying either IKZF3 mutation or high IKZF3 expression was associated with overexpression of BCR/NF-κB pathway members and reduced sensitivity to BCR signaling inhibition by ibrutinib. Our results thus highlight IKZF3 oncogenic function in CLL via transcriptional dysregulation and demonstrate that this pro-survival function can be achieved by either somatic mutation or overexpression of this CLL driver. This emphasizes the need for combinatorial approaches to overcome IKZF3-mediated BCR inhibitor resistance.},
langid = {english},
pmcid = {PMC8034546},
keywords = {Animals,B-Lymphocytes,BCR signaling,CLL,Humans,Ikaros Transcription Factor,IKZF3,Leukemia Lymphocytic Chronic B-Cell,Mice,Mice Inbred C57BL,Mice Inbred NOD,murine mode,Mutation,NF-kappa B,NF-κB,Receptors Antigen B-Cell,Signal Transduction,Transcription Genetic},
file = {/Users/rmorin/Zotero/storage/52PQRRWL/Lazarian et al. - 2021 - A hotspot mutation in transcription factor IKZF3 d.pdf}
}
@article{zhangDisruptionKMT2DPerturbs2015,
title = {Disruption of {{KMT2D}} Perturbs Germinal Center {{B}} Cell Development and Promotes Lymphomagenesis},
author = {Zhang, Jiyuan and Dominguez-Sola, David and Hussein, Shafinaz and Lee, Ji-Eun and Holmes, Antony B. and Bansal, Mukesh and Vlasevska, Sofija and Mo, Tongwei and Tang, Hongyan and Basso, Katia and Ge, Kai and Dalla-Favera, Riccardo and Pasqualucci, Laura},
date = {2015-10},
journaltitle = {Nature Medicine},
shortjournal = {Nat Med},
volume = {21},
number = {10},
eprint = {26366712},
eprinttype = {pmid},
pages = {1190--1198},
issn = {1546-170X},
doi = {10.1038/nm.3940},
abstract = {Mutations in the gene encoding the KMT2D (or MLL2) methyltransferase are highly recurrent and occur early during tumorigenesis in diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL). However, the functional consequences of these mutations and their role in lymphomagenesis are unknown. Here we show that FL- and DLBCL-associated KMT2D mutations impair KMT2D enzymatic activity, leading to diminished global H3K4 methylation in germinal-center (GC) B cells and DLBCL cells. Conditional deletion of Kmt2d early during B cell development, but not after initiation of the GC reaction, results in an increase in GC B cells and enhances B cell proliferation in mice. Moreover, genetic ablation of Kmt2d in mice overexpressing Bcl2 increases the incidence of GC-derived lymphomas resembling human tumors. These findings suggest that KMT2D acts as a tumor suppressor gene whose early loss facilitates lymphomagenesis by remodeling the epigenetic landscape of the cancer precursor cells. Eradication of KMT2D-deficient cells may thus represent a rational therapeutic approach for targeting early tumorigenic events.},
langid = {english},
pmcid = {PMC5145002},
keywords = {Animals,B-Lymphocytes,Cell Proliferation,DNA Methylation,DNA-Binding Proteins,Epigenesis Genetic,Gene Silencing,Germinal Center,Humans,Lymphoma Large B-Cell Diffuse,Mice,Mutation Missense,Neoplasm Proteins,Transcription Genetic},
file = {/Users/rmorin/Zotero/storage/3WZ3HYIK/Zhang et al. - 2015 - Disruption of KMT2D perturbs germinal center B cel.pdf}
}
@article{choiLossKLHL6Promotes2018,
title = {Loss of {{KLHL6}} Promotes Diffuse Large {{B-cell}} Lymphoma Growth and Survival by Stabilizing the {{mRNA}} Decay Factor Roquin2},
author = {Choi, Jaewoo and Lee, Kyutae and Ingvarsdottir, Kristin and Bonasio, Roberto and Saraf, Anita and Florens, Laurence and Washburn, Michael P. and Tadros, Saber and Green, Michael R. and Busino, Luca},
date = {2018-05},
journaltitle = {Nature Cell Biology},
shortjournal = {Nat Cell Biol},
volume = {20},
number = {5},
eprint = {29695787},
eprinttype = {pmid},
pages = {586--596},
issn = {1476-4679},
doi = {10.1038/s41556-018-0084-5},
abstract = {Kelch-like protein 6 (KLHL6) is an uncharacterized gene mutated in diffuse large B-cell lymphoma (DLBCL). Here we report that KLHL6 assembles with cullin3 to form a functional cullin-RING ubiquitin ligase. Mutations in KLHL6 inhibit its ligase activity by disrupting the interaction with cullin3. Loss of KLHL6 favours DLBCL growth and survival both in vitro and in xenograft models. We further established that the mRNA decay factor roquin2 is a substrate of KLHL6. Degradation of roquin2 is dependent on B-cell receptor activation, and requires the integrity of the Tyr691 residue in roquin2 that is essential for its interaction with KLHL6. A non-degradable roquin2(Y691F) mutant requires its RNA-binding ability to phenocopy the effect of KLHL6 loss. Stabilization of roquin2 promotes mRNA decay of the tumour suppressor and NF-κB pathway inhibitor, tumour necrosis factor-α-inducible gene 3. Collectively, our findings uncover the tumour suppressing mechanism of KLHL6.},
langid = {english},
pmcid = {PMC5926793},
keywords = {Animals,Carrier Proteins,Cell Line Tumor,Cell Proliferation,Cell Survival,Gene Expression Regulation Enzymologic,Gene Expression Regulation Neoplastic,HEK293 Cells,Humans,Lymphoma Large B-Cell Diffuse,Mice Inbred NOD,Mice SCID,Mutation,NF-kappa B,Protein Stability,Proteolysis,Receptors Antigen B-Cell,Repressor Proteins,RNA Messenger,RNA Stability,Signal Transduction,Tumor Necrosis Factor alpha-Induced Protein 3,Tumor Suppressor Proteins,Tyrosine,Ubiquitination},
}
@article{mansouriFunctionalLossIkBe2015,
title = {Functional Loss of {{IκBε}} Leads to {{NF-κB}} Deregulation in Aggressive Chronic Lymphocytic Leukemia},
author = {Mansouri, Larry and Sutton, Lesley-Ann and Ljungström, Viktor and Bondza, Sina and Arngården, Linda and Bhoi, Sujata and Larsson, Jimmy and Cortese, Diego and Kalushkova, Antonia and Plevova, Karla and Young, Emma and Gunnarsson, Rebeqa and Falk-Sörqvist, Elin and Lönn, Peter and Muggen, Alice F. and Yan, Xiao-Jie and Sander, Birgitta and Enblad, Gunilla and Smedby, Karin E. and Juliusson, Gunnar and Belessi, Chrysoula and Rung, Johan and Chiorazzi, Nicholas and Strefford, Jonathan C. and Langerak, Anton W. and Pospisilova, Sarka and Davi, Frederic and Hellström, Mats and Jernberg-Wiklund, Helena and Ghia, Paolo and Söderberg, Ola and Stamatopoulos, Kostas and Nilsson, Mats and Rosenquist, Richard},
date = {2015-06-01},
journaltitle = {The Journal of Experimental Medicine},
shortjournal = {J Exp Med},
volume = {212},
number = {6},
eprint = {25987724},
eprinttype = {pmid},
pages = {833--843},
issn = {1540-9538},
doi = {10.1084/jem.20142009},
abstract = {NF-κB is constitutively activated in chronic lymphocytic leukemia (CLL); however, the implicated molecular mechanisms remain largely unknown. Thus, we performed targeted deep sequencing of 18 core complex genes within the NF-κB pathway in a discovery and validation CLL cohort totaling 315 cases. The most frequently mutated gene was NFKBIE (21/315 cases; 7\%), which encodes IκBε, a negative regulator of NF-κB in normal B cells. Strikingly, 13 of these cases carried an identical 4-bp frameshift deletion, resulting in a truncated protein. Screening of an additional 377 CLL cases revealed that NFKBIE aberrations predominated in poor-prognostic patients and were associated with inferior outcome. Minor subclones and/or clonal evolution were also observed, thus potentially linking this recurrent event to disease progression. Compared with wild-type patients, NFKBIE-deleted cases showed reduced IκBε protein levels and decreased p65 inhibition, along with increased phosphorylation and nuclear translocation of p65. Considering the central role of B cell receptor (BcR) signaling in CLL pathobiology, it is notable that IκBε loss was enriched in aggressive cases with distinctive stereotyped BcR, likely contributing to their poor prognosis, and leading to an altered response to BcR inhibitors. Because NFKBIE deletions were observed in several other B cell lymphomas, our findings suggest a novel common mechanism of NF-κB deregulation during lymphomagenesis.},
langid = {english},
pmcid = {PMC4451125},
keywords = {Cell Nucleus,Cell Survival,Chromosome Aberrations,Cohort Studies,Cytoplasm,DNA Mutational Analysis,Frameshift Mutation,Gene Deletion,Gene Expression Profiling,Gene Expression Regulation Leukemic,Humans,I-kappa B Kinase,Leukemia Lymphocytic Chronic B-Cell,Lymphoma B-Cell,Lymphoma B-Cell Marginal Zone,Lymphoma Mantle-Cell,NF-kappa B,Oligonucleotide Array Sequence Analysis,Receptors Antigen B-Cell,Signal Transduction,Treatment Outcome},
file = {/Users/rmorin/Zotero/storage/IFEN6256/Mansouri et al. - 2015 - Functional loss of IκBε leads to NF-κB deregulatio.pdf}
}
@article{saffieFBXW7TriggersDegradation2020,
title = {{{FBXW7 Triggers Degradation}} of {{KMT2D}} to {{Favor Growth}} of {{Diffuse Large B-cell Lymphoma Cells}}},
author = {Saffie, Rizwan and Zhou, Nan and Rolland, Delphine and Önder, Özlem and Basrur, Venkatesha and Campbell, Sydney and Wellen, Kathryn E. and Elenitoba-Johnson, Kojo S. J. and Capell, Brian C. and Busino, Luca},
date = {2020-06-15},
journaltitle = {Cancer Research},
shortjournal = {Cancer Res},
volume = {80},
number = {12},
eprint = {32350066},
eprinttype = {pmid},
pages = {2498--2511},
issn = {1538-7445},
doi = {10.1158/0008-5472.CAN-19-2247},
abstract = {Mature B-cell neoplasms are the fifth most common neoplasm. Due to significant heterogeneity at the clinical and genetic levels, current therapies for these cancers fail to provide long-term cures. The clinical success of proteasome inhibition for the treatment of multiple myeloma and B-cell lymphomas has made the ubiquitin pathway an important emerging therapeutic target. In this study, we assessed the role of the E3 ligase FBXW7 in mature B-cell neoplasms. FBXW7 targeted the frequently inactivated tumor suppressor KMT2D for protein degradation, subsequently regulating gene expression signatures related to oxidative phosphorylation (OxPhos). Loss of FBXW7 inhibited diffuse large B-cell lymphoma cell growth and further sensitized cells to OxPhos inhibition. These data elucidate a novel mechanism of regulation of KMT2D levels by the ubiquitin pathway and uncover a role of FBXW7 in regulating oxidative phosphorylation in B-cell malignancies. SIGNIFICANCE: These findings characterize FBXW7 as a prosurvival factor in B-cell lymphoma via degradation of the chromatin modifier KMT2D.},
langid = {english},
pmcid = {PMC7417195},
keywords = {Animals,Cell Line Tumor,Cell Proliferation,Chromatin,DNA-Binding Proteins,F-Box-WD Repeat-Containing Protein 7,Female,Gene Expression Regulation Neoplastic,Gene Knockout Techniques,HEK293 Cells,Humans,Lymphoma Large B-Cell Diffuse,Mice,Neoplasm Proteins,Oxidative Phosphorylation,Proteolysis,RNA Small Interfering,Signal Transduction,Ubiquitin,Xenograft Model Antitumor Assays},
file = {/Users/rmorin/Zotero/storage/5KJ466DP/Saffie et al. - 2020 - FBXW7 Triggers Degradation of KMT2D to Favor Growt.pdf;/Users/rmorin/Zotero/storage/RQSU3BV9/Saffie et al. - 2020 - FBXW7 Triggers Degradation of KMT2D to Favor Growt.pdf}
}
@article{katoUnderstandingFunctionstructureFunctionmutation2003,
title = {Understanding the Function-Structure and Function-Mutation Relationships of P53 Tumor Suppressor Protein by High-Resolution Missense Mutation Analysis},
author = {Kato, Shunsuke and Han, Shuang-Yin and Liu, Wen and Otsuka, Kazunori and Shibata, Hiroyuki and Kanamaru, Ryunosuke and Ishioka, Chikashi},
date = {2003-07-08},
journaltitle = {Proceedings of the National Academy of Sciences of the United States of America},
shortjournal = {Proc Natl Acad Sci U S A},
volume = {100},
number = {14},
eprint = {12826609},
eprinttype = {pmid},
pages = {8424--8429},
issn = {0027-8424},
doi = {10.1073/pnas.1431692100},
abstract = {Inactivation of the tumor suppressor p53 by missense mutations is the most frequent genetic alteration in human cancers. The common missense mutations in the TP53 gene disrupt the ability of p53 to bind to DNA and consequently to transactivate downstream genes. However, it is still not fully understood how a large number of the remaining mutations affect p53 structure and function. Here, we used a comprehensive site-directed mutagenesis technique and a yeast-based functional assay to construct, express, and evaluate 2,314 p53 mutants representing all possible amino acid substitutions caused by a point mutation throughout the protein (5.9 substitutions per residue), and correlated p53 function with structure- and tumor-derived mutations. This high-resolution mutation analysis allows evaluation of previous predictions and hypotheses through interrelation of function, structure and mutation.},
langid = {english},
pmcid = {PMC166245},
keywords = {Amino Acid Substitution,DNA Repair,Genes p53,Genes Reporter,Humans,Luciferases,Models Molecular,Mutagenesis Site-Directed,Mutation Missense,Point Mutation,Polymerase Chain Reaction,Protein Conformation,Protein Structure Tertiary,Recombinant Fusion Proteins,Saccharomyces cerevisiae,Structure-Activity Relationship,Transcriptional Activation,Tumor Suppressor Protein p53},
file = {/Users/rmorin/Zotero/storage/K7XZZIYN/Kato et al. - 2003 - Understanding the function-structure and function-.pdf}
}
@article{skalniakRegulatoryFeedbackLoop2009,
title = {Regulatory Feedback Loop between {{NF-kappaB}} and {{MCP-1-induced}} Protein 1 {{RNase}}},
author = {Skalniak, Lukasz and Mizgalska, Danuta and Zarebski, Adrian and Wyrzykowska, Paulina and Koj, Aleksander and Jura, Jolanta},
date = {2009-10},
journaltitle = {The FEBS journal},
shortjournal = {FEBS J},
volume = {276},
number = {20},
eprint = {19747262},
eprinttype = {pmid},
pages = {5892--5905},
issn = {1742-4658},
doi = {10.1111/j.1742-4658.2009.07273.x},
abstract = {A novel gene ZC3H12A, encoding MCP-1-induced protein 1 (MCPIP), was recently identified in human peripheral blood monocytes treated with monocyte chemotactic protein 1 (MCP-1) and in human monocyte-derived macrophages stimulated with interleukin (IL)-1beta. These experiments revealed that the gene undergoes rapid and potent transcription induction upon stimulation with proinflammatory molecules, such as MCP-1, IL-1beta, tumour necrosis factor alpha and lipopolysaccharide. Here we show that the induction of ZC3H12A by IL-1beta is predominantly NF-kappaB-dependent because inhibition of this signalling pathway results in the impairment of ZC3H12A transcription activation. Our results indicate the presence of an IL-1beta-responding region within the second intron of the ZC3H12A gene, which contains four functional NF-kappaB-binding sites. Therefore, we propose that this transcription enhancer transduces a ZC3H12A transcription-inducing signal after IL-1beta stimulation. Recent reports suggest that MCPIP acts as a negative regulator of inflammatory processes because it is engaged in the degradation of transcripts coding for certain proinflammatory cytokines. Our observations provide evidence for a novel negative feedback loop in the activation of NF-kappaB and point to potential significance of MCPIP in the treatment of various pathological states, such as diabetes or cancer that involve disturbances in the functioning of the NF-kappaB system.},
langid = {english},
keywords = {Base Sequence,Binding Sites,Blotting Western,Cell Line Tumor,Chromatin Immunoprecipitation,Electrophoretic Mobility Shift Assay,Humans,I-kappa B Proteins,Interleukin-1beta,Molecular Sequence Data,Mutagenesis Site-Directed,NF-kappa B,Polymerase Chain Reaction,Ribonucleases,Signal Transduction,Transcription Factors,Transcription Genetic,Transcription Initiation Site}
}
@article{wangFasFADDDeathDomain2010,
title = {The {{Fas-FADD}} Death Domain Complex Structure Reveals the Basis of {{DISC}} Assembly and Disease Mutations},
author = {Wang, Liwei and Yang, Jin Kuk and Kabaleeswaran, Venkataraman and Rice, Amanda J. and Cruz, Anthony C. and Park, Ah Young and Yin, Qian and Damko, Ermelinda and Jang, Se Bok and Raunser, Stefan and Robinson, Carol V. and Siegel, Richard M. and Walz, Thomas and Wu, Hao},
date = {2010-11},
journaltitle = {Nature Structural \& Molecular Biology},
shortjournal = {Nat Struct Mol Biol},
volume = {17},
number = {11},
eprint = {20935634},
eprinttype = {pmid},
pages = {1324--1329},
issn = {1545-9985},
doi = {10.1038/nsmb.1920},
abstract = {The death-inducing signaling complex (DISC) formed by the death receptor Fas, the adaptor protein FADD and caspase-8 mediates the extrinsic apoptotic program. Mutations in Fas that disrupt the DISC cause autoimmune lymphoproliferative syndrome (ALPS). Here we show that the Fas-FADD death domain (DD) complex forms an asymmetric oligomeric structure composed of 5-7 Fas DD and 5 FADD DD, whose interfaces harbor ALPS-associated mutations. Structure-based mutations disrupt the Fas-FADD interaction in vitro and in living cells; the severity of a mutation correlates with the number of occurrences of a particular interaction in the structure. The highly oligomeric structure explains the requirement for hexameric or membrane-bound FasL in Fas signaling. It also predicts strong dominant negative effects from Fas mutations, which are confirmed by signaling assays. The structure optimally positions the FADD death effector domain (DED) to interact with the caspase-8 DED for caspase recruitment and higher-order aggregation.},
langid = {english},
pmcid = {PMC2988912},
keywords = {Amino Acid Sequence,Animals,Apoptosis,Autoimmune Lymphoproliferative Syndrome,Caspase 8,Cell Line,fas Receptor,Fas-Associated Death Domain Protein,Humans,Mice,Models Molecular,Molecular Sequence Data,Mutation,Protein Structure Tertiary,Sequence Alignment,Spectrometry Mass Electrospray Ionization,Tandem Mass Spectrometry},
}
@article{zmajkovicovaGenotypephenotypeCorrelationsWHIM2022,
title = {Genotype-Phenotype Correlations in {{WHIM}} Syndrome: A Systematic Characterization of {{CXCR4WHIM}} Variants},
shorttitle = {Genotype-Phenotype Correlations in {{WHIM}} Syndrome},
author = {Zmajkovicova, Katarina and Pawar, Sumit and Maier-Munsa, Sabine and Maierhofer, Barbara and Wiest, Ivana and Skerlj, Renato and Taveras, Arthur G. and Badarau, Adriana},
date = {2022-09},
journaltitle = {Genes and Immunity},
shortjournal = {Genes Immun},
volume = {23},
number = {6},
eprint = {36089616},
eprinttype = {pmid},
pages = {196--204},
issn = {1476-5470},
doi = {10.1038/s41435-022-00181-9},
abstract = {Warts, hypogammaglobulinemia, infections, myelokathexis (WHIM) syndrome is a rare primary immunodeficiency predominantly caused by heterozygous gain-of-function mutations in CXCR4 C-terminus. We assessed genotype-phenotype correlations for known pathogenic CXCR4 variants and in vitro response of each variant to mavorixafor, an investigational CXCR4 antagonist. We used cell-based assays to analyze CXCL12-induced receptor trafficking and downstream signaling of 14 pathogenic CXCR4 variants previously identified in patients with WHIM syndrome. All CXCR4 variants displayed impaired receptor trafficking, hyperactive downstream signaling, and enhanced chemotaxis in response to CXCL12. Mavorixafor inhibited CXCL12-dependent signaling and hyperactivation in cells harboring CXCR4WHIM mutations. A strong correlation was found between CXCR4 internalization defect and severity of blood leukocytopenias and infection susceptibility, and between AKT activation and immunoglobulin A level and CD4+ T-cell counts. This study is the first to show WHIM syndrome clinical phenotype variability as a function of both CXCR4WHIM genotype diversity and associated functional dysregulation. Our findings suggest that CXCR4 internalization may be used to assess the pathogenicity of CXCR4 variants in vitro and also as a potential WHIM-related disease biomarker. The investigational CXCR4 antagonist mavorixafor inhibited CXCL12-dependent signaling in all tested CXCR4-variant cell lines at clinically relevant concentrations.},
langid = {english},
pmcid = {PMC9519442},
keywords = {Agammaglobulinemia,Aminoquinolines,Benzimidazoles,Biomarkers,Butylamines,Genetic Association Studies,Humans,Immunoglobulin A,Immunologic Deficiency Syndromes,Neutropenia,Primary Immunodeficiency Diseases,Proto-Oncogene Proteins c-akt,Receptors CXCR4,Warts},
}
@article{ramirez-komoSpontaneousLossLineage2017,
title = {Spontaneous Loss of {{B}} Lineage Transcription Factors Leads to Pre-{{B}} Leukemia in {{Ebf1}}+/-{{Bcl-xLTg}} Mice},
author = {Ramírez-Komo, J. A. and Delaney, M. A. and Straign, D. and Lukin, K. and Tsang, M. and Iritani, B. M. and Hagman, J.},
date = {2017-07-10},
journaltitle = {Oncogenesis},
shortjournal = {Oncogenesis},
volume = {6},
number = {7},
eprint = {28692033},
eprinttype = {pmid},
pages = {e355},
issn = {2157-9024},
doi = {10.1038/oncsis.2017.55},
abstract = {Early B-cell factor 1 (EBF1) plays a central role in B-cell lineage specification and commitment. Loss of this critical transcription factor is strongly associated with high-risk, relapsed and therapy-resistant B-cell-acute lymphoblastic leukemia, especially in children. However, Ebf1 haploinsufficient mice exhibit a normal lifespan. To determine whether prolonged survival of B cells would enable tumorigenesis in Ebf1 haploinsufficient animals, we generated Ebf1+/-Bcl-xLTg mice, which express the anti-apoptotic factor Bcl-xL in B cells. Approximately half of Ebf1+/-Bcl-xLTg mice develop aggressive oligoclonal leukemia as they age, which engrafts in congenic wild-type recipients without prior conditioning. The neoplastic cells display a pre-B phenotype and express early developmental- and natural killer cell/myeloid-markers inappropriately. In addition, we found tumor cell-specific loss of several transcription factors critical for maintaining differentiation: EBF1, TCF3 and RUNX1. However, in the majority of tumors, loss of Ebf1 expression was not due to loss of heterozygosity. This is the first spontaneous mouse model of pre-B leukemia to demonstrate inappropriate expression of non-B-cell-specific genes associated with loss of Ebf1, Tcf3 and Runx1 expression.},
langid = {english},
pmcid = {PMC5541707},
}
@article{wangETV6MutationCohort2014,
title = {{{ETV6}} Mutation in a Cohort of 970 Patients with Hematologic Malignancies},
author = {Wang, Qinrong and Dong, Shasha and Yao, Hong and Wen, Lijun and Qiu, Huiying and Qin, Llili and Ma, Liang and Chen, Suning},
date = {2014-10},
journaltitle = {Haematologica},
shortjournal = {Haematologica},
volume = {99},
number = {10},
eprint = {24997145},
eprinttype = {pmid},
pages = {e176-178},
issn = {1592-8721},
doi = {10.3324/haematol.2014.104406},
langid = {english},
pmcid = {PMC4181263},
keywords = {Cohort Studies,ETS Translocation Variant 6 Protein,ETV6,hematologic malignancies,Hematologic Neoplasms,Humans,Mutation,mutations,Proto-Oncogene Proteins c-ets,Repressor Proteins},
}
@article{sneeringerCoordinatedActivitiesWildtype2010,
title = {Coordinated Activities of Wild-Type plus Mutant {{EZH2}} Drive Tumor-Associated Hypertrimethylation of Lysine 27 on Histone {{H3}} ({{H3K27}}) in Human {{B-cell}} Lymphomas},
author = {Sneeringer, Christopher J. and Scott, Margaret Porter and Kuntz, Kevin W. and Knutson, Sarah K. and Pollock, Roy M. and Richon, Victoria M. and Copeland, Robert A.},
date = {2010-12-07},
journaltitle = {Proceedings of the National Academy of Sciences of the United States of America},
shortjournal = {Proc Natl Acad Sci U S A},
volume = {107},
number = {49},
eprint = {21078963},
eprinttype = {pmid},
pages = {20980--20985},
issn = {1091-6490},
doi = {10.1073/pnas.1012525107},
abstract = {EZH2, the catalytic subunit of the PRC2 complex, catalyzes the mono- through trimethylation of lysine 27 on histone H3 (H3K27). Histone H3K27 trimethylation is a mechanism for suppressing transcription of specific genes that are proximal to the site of histone modification. Point mutations of the EZH2 gene (Tyr641) have been reported to be linked to subsets of human B-cell lymphoma. The mutant allele is always found associated with a wild-type allele (heterozygous) in disease cells, and the mutations were reported to ablate the enzymatic activity of the PRC2 complex for methylating an unmodified peptide substrate. Here we demonstrate that the WT enzyme displays greatest catalytic efficiency (k(cat)/K) for the zero to monomethylation reaction of H3K27 and diminished efficiency for subsequent (mono- to di- and di- to trimethylation) reactions. In stark contrast, the disease-associated Y641 mutations display very limited ability to perform the first methylation reaction, but have enhanced catalytic efficiency for the subsequent reactions, relative to the WT enzyme. These results imply that the malignant phenotype of disease requires the combined activities of a H3K27 monomethylating enzyme (PRC2 containing WT EZH2 or EZH1) together with the mutant PRC2s for augmented conversion of H3K27 to the trimethylated form. To our knowledge, this is the first example of a human disease that is dependent on the coordinated activities of normal and disease-associated mutant enzymatic function.},
langid = {english},
pmcid = {PMC3000297},
file = {/Users/rmorin/Zotero/storage/QKW38HUB/Sneeringer et al. - 2010 - Coordinated activities of wild-type plus mutant EZ.pdf}
}
@article{fangazioGeneticMechanismsHLAI2021,
title = {Genetic Mechanisms of {{HLA-I}} Loss and Immune Escape in Diffuse Large {{B}} Cell Lymphoma},
author = {Fangazio, Marco and Ladewig, Erik and Gomez, Karen and Garcia-Ibanez, Laura and Kumar, Rahul and Teruya-Feldstein, Julie and Rossi, Davide and Filip, Ioan and Pan-Hammarström, Qiang and Inghirami, Giorgio and Boldorini, Renzo and Ott, German and Staiger, Annette M. and Chapuy, Björn and Gaidano, Gianluca and Bhagat, Govind and Basso, Katia and Rabadan, Raul and Pasqualucci, Laura and Dalla-Favera, Riccardo},
date = {2021-06-01},
journaltitle = {Proceedings of the National Academy of Sciences of the United States of America},
shortjournal = {Proc Natl Acad Sci U S A},
volume = {118},
number = {22},
eprint = {34050029},
eprinttype = {pmid},
pages = {e2104504118},
issn = {1091-6490},
doi = {10.1073/pnas.2104504118},
abstract = {Fifty percent of diffuse large B cell lymphoma (DLBCL) cases lack cell-surface expression of the class I major histocompatibility complex (MHC-I), thus escaping recognition by cytotoxic T cells. Here we show that, across B cell lymphomas, loss of MHC-I, but not MHC-II, is preferentially restricted to DLBCL. To identify the involved mechanisms, we performed whole exome and targeted HLA deep-sequencing in 74 DLBCL samples, and found somatic inactivation of B2M and the HLA-I loci in 80\% (34 of 42) of MHC-INEG tumors. Furthermore, 70\% (22 of 32) of MHC-IPOS DLBCLs harbored monoallelic HLA-I genetic alterations (MHC-IPOS/mono), indicating allele-specific inactivation. MHC-INEG and MHC-IPOS/mono cases harbored significantly higher mutational burden and inferred neoantigen load, suggesting potential coselection of HLA-I loss and sustained neoantigen production. Notably, the analysis of {$>$}500,000 individuals across different cancer types revealed common germline HLA-I homozygosity, preferentially in DLBCL. In mice, germinal-center B cells lacking HLA-I expression did not progress to lymphoma and were counterselected in the context of oncogene-driven lymphomagenesis, suggesting that additional events are needed to license immune evasion. These results suggest a multistep process of HLA-I loss in DLBCL development including both germline and somatic events, and have direct implications for the pathogenesis and immunotherapeutic targeting of this disease.},
langid = {english},
pmcid = {PMC8179151},
keywords = {beta 2-Microglobulin,Cell Line Tumor,Cell Transformation Neoplastic,Cytidine Deaminase,DLBCL,Gene Silencing,Histocompatibility Antigens Class I,HLA,Humans,immune evasion,Lymphoma Large B-Cell Diffuse,Proto-Oncogene Proteins c-bcl-6},
}
@article{kannengiesserFunctionalStructuralGenetic2009,
title = {Functional, Structural, and Genetic Evaluation of 20 {{CDKN2A}} Germ Line Mutations Identified in Melanoma-Prone Families or Patients},
author = {Kannengiesser, Caroline and Brookes, Sharon and family=Arroyo, given=Anna Gutierrez, prefix=del, useprefix=true and Pham, Danielle and Bombled, Johny and Barrois, Michel and Mauffret, Olivier and Avril, Marie-Françoise M. and Chompret, Agnès and Lenoir, Gilbert M. and Sarasin, Alain and {French Hereditary Melanoma Study Group} and Peters, Gordon and Bressac-de Paillerets, Brigitte},
date = {2009-04},
journaltitle = {Human Mutation},
shortjournal = {Hum Mutat},
volume = {30},
number = {4},
eprint = {19260062},
eprinttype = {pmid},
pages = {564--574},
issn = {1098-1004},
doi = {10.1002/humu.20845},
abstract = {Germline mutations of the CDKN2A gene are found in melanoma-prone families and individuals with multiple sporadic melanomas. The encoded protein, p16(INK4A), comprises four ankyrin-type repeats, and the mutations, most of which are missense and occur throughout the entire coding region, can disrupt the conformation of these structural motifs as well as the association of p16(INK4a) with its physiological targets, the cyclin-dependent kinases (CDKs) CDK4 and CDK6. Assessing pathogenicity of nonsynonymous mutations is critical to evaluate melanoma risk in carriers. In the current study, we investigate 20 CDKN2A germline mutations whose effects on p16(INK4A) structure and function have not been previously documented (Thr18\_Ala19dup, Gly23Asp, Arg24Gln, Gly35Ala, Gly35Val, Ala57Val, Ala60Val, Ala60Arg, Leu65dup, Gly67Arg, Gly67\_Asn71del, Glu69Gly, Asp74Tyr, Thr77Pro, Arg80Pro, Pro81Thr, Arg87Trp, Leu97Arg, Arg99Pro, and [Leu113Leu;Pro114Ser]). By considering genetic information, the predicted impact of each variant on the protein structure, its ability to interact with CDK4 and impede cell proliferation in experimental settings, we conclude that 18 of the 20 CDKN2A variants can be classed as loss of function mutations, whereas the results for two remain ambiguous. Discriminating between mutant and neutral variants of p16(INK4A) not only adds to our understanding of the functionally critical residues in the protein but provides information that can be used for melanoma risk prediction.},
langid = {english},
keywords = {Cell Line,Cell Proliferation,Cyclin-Dependent Kinase 4,Cyclin-Dependent Kinase Inhibitor p16,Family Health,Genetic Testing,Germ-Line Mutation,Humans,Melanoma,Models Molecular,Mutation Missense,Protein Binding,Protein Structure Tertiary},
}
@article{huFollicularLymphomaassociatedBTK2021,
title = {Follicular {{Lymphoma-associated BTK Mutations}} Are {{Inactivating Resulting}} in {{Augmented AKT Activation}}},
author = {Hu, Nan and Wang, Fangyang and Sun, Tianyu and Xu, Zhengfan and Zhang, Jing and Bernard, Denzil and Xu, Shilin and Wang, Shaomeng and Kaminski, Mark and Devata, Suma and Phillips, Tycel and Malek, Sami N.},
date = {2021-04-15},
journaltitle = {Clinical Cancer Research: An Official Journal of the American Association for Cancer Research},
shortjournal = {Clin Cancer Res},
volume = {27},
number = {8},
eprint = {33419778},
eprinttype = {pmid},
pages = {2301--2313},
issn = {1557-3265},
doi = {10.1158/1078-0432.CCR-20-3741},
abstract = {PURPOSE: On the basis of the recent discovery of mutations in Bruton tyrosine kinase (BTK) in follicular lymphoma, we studied their functional properties. EXPERIMENTAL DESIGN: We identified novel somatic BTK mutations in 7\% of a combined total of 139 follicular lymphoma and 11 transformed follicular lymphoma cases, none of which had received prior treatment with B-cell receptor (BCR) targeted drugs. We reconstituted wild-type (WT) and mutant BTK into various engineered lymphoma cell lines. We measured BCR-induced signal transduction events in engineered cell lines and primary human follicular lymphoma B cells. RESULTS: We uncovered that all BTK mutants destabilized the BTK protein and some created BTK kinase-dead mutants. The phospholipase C gamma 2 (PLCγ2) is a substrate of BTK but the BTK mutants did not alter PLCγ2 phosphorylation. Instead, we discovered that BTK mutants induced an exaggerated AKT phosphorylation phenotype in anti-Ig-treated recombinant lymphoma cell lines. The short hairpin RNA-mediated knockdown of BTK expression in primary human nonmalignant lymph node-derived B cells resulted in strong anti-Ig-induced AKT activation, as did the degradation of BTK protein in cell lines using ibrutinib-based proteolysis targeting chimera. Finally, through analyses of primary human follicular lymphoma B cells carrying WT or mutant BTK, we detected elevated AKT phosphorylation following surface Ig crosslinking in all follicular lymphoma B cells, including all BTK-mutant follicular lymphoma. The augmented AKT phosphorylation following BCR crosslinking could be abrogated by pretreatment with a PI3Kδ inhibitor. CONCLUSIONS: Altogether, our data uncover novel unexpected properties of follicular lymphoma-associated BTK mutations with direct implications for targeted therapy development in follicular lymphoma.See related commentary by Afaghani and Taylor, p. 2123.},
langid = {english},
pmcid = {PMC8046715},
keywords = {Agammaglobulinaemia Tyrosine Kinase,Cell Line Tumor,Class I Phosphatidylinositol 3-Kinases,DNA Mutational Analysis,Gene Knockdown Techniques,HEK293 Cells,Humans,Loss of Function Mutation,Lymphoma Follicular,Mutagenesis Site-Directed,Phospholipase C gamma,Phosphorylation,Primary Cell Culture,Protein Stability,Proto-Oncogene Proteins c-akt},
}
@article{almasmoumFrequentLossBTG12021,
title = {Frequent Loss of {{BTG1}} Activity and Impaired Interactions with the {{Caf1}} Subunit of the {{Ccr4-Not}} Deadenylase in Non-{{Hodgkin}} Lymphoma},
author = {Almasmoum, Hibah Ali and Airhihen, Blessing and Seedhouse, Claire and Winkler, Gerlof Sebastiaan},
date = {2021-02},
journaltitle = {Leukemia \& Lymphoma},
shortjournal = {Leuk Lymphoma},
volume = {62},
number = {2},
eprint = {33021411},
eprinttype = {pmid},
pages = {281--290},
issn = {1029-2403},
doi = {10.1080/10428194.2020.1827243},
abstract = {Mutations in the highly similar genes B-cell translocation gene 1 (BTG1) and BTG2 are identified in approximately 10-15\% of non-Hodgkin lymphoma cases, which may suggest a direct involvement of BTG1 and BTG2 in malignant transformation. However, it is unclear whether or how disease-associated mutations impair the function of these genes. Therefore, we selected 16 BTG1 variants based on in silico analysis. We then evaluated (i) the ability of these variants to interact with the known protein-binding partners CNOT7 and CNOT8, which encode the Caf1 catalytic subunit of the Ccr4-Not deadenylase complex; (ii) the activity of the variant proteins in cell cycle progression; (iii) translational repression; and (iv) mRNA degradation. Based on these analyses, we conclude that mutations in BTG1 may contribute to malignant transformation and tumor cell proliferation by interfering with its anti-proliferative activity and ability to interact with CNOT7 and CNOT8.},
langid = {english},
keywords = {BTG1,BTG2,Ccr4–Not,Cell Proliferation,Exoribonucleases,Humans,Immediate-Early Proteins,Lymphoma and Hodgkin disease,Lymphoma Non-Hodgkin,mRNA decay,Neoplasm Proteins,Protein Binding,Receptors CCR4,Repressor Proteins,Transcription Factors,Tumor Suppressor Proteins},
}
@article{wanMechanismActivationRAFERK2004,
title = {Mechanism of Activation of the {{RAF-ERK}} Signaling Pathway by Oncogenic Mutations of {{B-RAF}}},
author = {Wan, Paul T. C. and Garnett, Mathew J. and Roe, S. Mark and Lee, Sharlene and Niculescu-Duvaz, Dan and Good, Valerie M. and Jones, C. Michael and Marshall, Christopher J. and Springer, Caroline J. and Barford, David and Marais, Richard and {Cancer Genome Project}},
date = {2004-03-19},
journaltitle = {Cell},
shortjournal = {Cell},
volume = {116},
number = {6},
eprint = {15035987},
eprinttype = {pmid},
pages = {855--867},
issn = {0092-8674},
doi = {10.1016/s0092-8674(04)00215-6},
abstract = {Over 30 mutations of the B-RAF gene associated with human cancers have been identified, the majority of which are located within the kinase domain. Here we show that of 22 B-RAF mutants analyzed, 18 have elevated kinase activity and signal to ERK in vivo. Surprisingly, three mutants have reduced kinase activity towards MEK in vitro but, by activating C-RAF in vivo, signal to ERK in cells. The structures of wild type and oncogenic V599EB-RAF kinase domains in complex with the RAF inhibitor BAY43-9006 show that the activation segment is held in an inactive conformation by association with the P loop. The clustering of most mutations to these two regions suggests that disruption of this interaction converts B-RAF into its active conformation. The high activity mutants signal to ERK by directly phosphorylating MEK, whereas the impaired activity mutants stimulate MEK by activating endogenous C-RAF, possibly via an allosteric or transphosphorylation mechanism.},
langid = {english},
keywords = {Allosteric Regulation,Animals,Catalytic Domain,Cell Transformation Neoplastic,Enzyme Inhibitors,Gene Expression Regulation Enzymologic,MAP Kinase Kinase 1,MAP Kinase Signaling System,Mice,Mitogen-Activated Protein Kinase Kinases,Mitogen-Activated Protein Kinases,Models Molecular,Molecular Conformation,Mutation,Neoplasms,NIH 3T3 Cells,Oncogenes,Oocytes,Phosphorylation,Phosphotransferases,Proto-Oncogene Proteins B-raf,Proto-Oncogene Proteins c-raf,Up-Regulation,Xenopus},
}
@article{masclePointMutationsBCL62003,
title = {Point Mutations in {{BCL6 DNA-binding}} Domain Reveal Distinct Roles for the Six Zinc Fingers},
author = {Mascle, Xavier and Albagli, Olivier and Lemercier, Claudie},
date = {2003-01-10},
journaltitle = {Biochemical and Biophysical Research Communications},
shortjournal = {Biochem Biophys Res Commun},
volume = {300},
number = {2},
eprint = {12504096},
eprinttype = {pmid},
pages = {391--396},
issn = {0006-291X},
doi = {10.1016/s0006-291x(02)02873-5},
abstract = {The B-cell lymphoma 6 (BCL6) gene encodes a transcriptional repressor containing six C-terminal Krüppel-like zinc fingers. The zinc finger (ZF) cluster is necessary and sufficient for interaction with both DNA and several proteins and for nuclear targeting. However, the functional specificity of the six ZFs in these cellular roles is unknown. To characterize this domain, we mutated individually each ZF of BCL6. Our results reveal that mutation of the two N-terminal ZFs does not impair cognate DNA-binding, cellular localization of the protein nor the transcriptional repression capacity of BCL6. By contrast, mutation of any of the remaining ZFs abolishes the binding of BCL6 to DNA in vitro and the transrepressive function of the protein in vivo. Finally, none of the six mutations affect the interaction between BCL6 and class II histone deacetylases. Thus our experiments demonstrate that BCL6 uses each of the four C-terminus ZFs for binding to a target sequence while the two amino terminal fingers are likely engaged in other unknown function(s).},
langid = {english},
keywords = {Amino Acid Sequence,Binding Sites,DNA-Binding Proteins,Gene Expression Regulation,HeLa Cells,Histone Deacetylases,Humans,Molecular Sequence Data,Point Mutation,Protein Structure Tertiary,Proto-Oncogene Proteins,Proto-Oncogene Proteins c-bcl-6,Repressor Proteins,Sequence Alignment,Transcription Factors,Transcription Genetic,Zinc Fingers},
}
@article{camachoATMGeneInactivation2002,
title = {{{ATM}} Gene Inactivation in Mantle Cell Lymphoma Mainly Occurs by Truncating Mutations and Missense Mutations Involving the Phosphatidylinositol-3 Kinase Domain and Is Associated with Increasing Numbers of Chromosomal Imbalances},
author = {Camacho, Emma and Hernández, Luis and Hernández, Silvia and Tort, Frederic and Bellosillo, Beatriz and Beà, Silvia and Bosch, Francesc and Montserrat, Emili and Cardesa, Antonio and Fernández, Pedro L. and Campo, Elias},
date = {2002-01-01},
journaltitle = {Blood},
shortjournal = {Blood},
volume = {99},
number = {1},
eprint = {11756177},
eprinttype = {pmid},
pages = {238--244},
issn = {0006-4971},
doi = {10.1182/blood.v99.1.238},
abstract = {The ataxia-telangiectasia mutated (ATM) gene codifies for a protein critically involved in the cellular response to DNA damage. ATM alterations have been observed in some sporadic lymphoproliferative disorders. The recurrent 11q22-23 deletions found in mantle cell lymphoma (MCL) suggest that ATM could be inactivated in these lymphomas. In this study, ATM gene alterations and protein expression were examined in 20 and 17 MCL tumor specimens, respectively. Previously, these patients had been examined for p53 and p14(ARF) gene status and analyzed by comparative genomic hybridization. Nine patients had 11q22-23 losses. Eight ATM gene mutations were detected in 7 patients. These alterations were 3 missense mutations in the phosphatidylinositol-3 kinase (PI-3K) domain and 5 truncating mutations, including 3 frameshifts, a nonsense mutation, and a substitution of the initial methionine. All truncating mutations were associated with lack of protein expression. Somatic origin was demonstrated in 3 mutations, whereas one mutation was carried heterozygously in the patient germ line. Chromosomal imbalances were significantly higher in typical MCL with ATM inactivation (7.8 +/- 1.3) than in tumors with the wild-type gene (3 +/- 1.1) (P =.001). Moreover, tumors with bi-allelic ATM alteration were associated with 3q gains (P =.015) and frequent extranodal involvement (P =.049). ATM gene alterations were not related to the histologic variant of the tumors, p53/p14(ARF) gene status, survival, or other clinicopathologic features of the patients. These findings indicate that ATM gene mutations in MCL are mainly truncating or missense mutations involving the PI-3K domain, and that may play a role in the pathogenesis of a subset of these tumors with increased numbers of chromosomal imbalances.},
langid = {english},
keywords = {Alleles,Ataxia Telangiectasia Mutated Proteins,Blotting Western,Cell Cycle Proteins,Chromosome Aberrations,Chromosomes Human Pair 11,DNA Mutational Analysis,DNA-Binding Proteins,Gene Deletion,Gene Expression,Humans,Lymphoma Mantle-Cell,Mutation,Mutation Missense,Phosphatidylinositol 3-Kinases,Polymorphism Genetic,Protein Serine-Threonine Kinases,Tumor Suppressor Proteins},
}
@article{yusufovaHistoneH1Loss2021,
title = {Histone {{H1}} Loss Drives Lymphoma by Disrupting {{3D}} Chromatin Architecture},
author = {Yusufova, Nevin and Kloetgen, Andreas and Teater, Matt and Osunsade, Adewola and Camarillo, Jeannie M. and Chin, Christopher R. and Doane, Ashley S. and Venters, Bryan J. and Portillo-Ledesma, Stephanie and Conway, Joseph and Phillip, Jude M. and Elemento, Olivier and Scott, David W. and Béguelin, Wendy and Licht, Jonathan D. and Kelleher, Neil L. and Staudt, Louis M. and Skoultchi, Arthur I. and Keogh, Michael-Christopher and Apostolou, Effie and Mason, Christopher E. and Imielinski, Marcin and Schlick, Tamar and David, Yael and Tsirigos, Aristotelis and Allis, C. David and Soshnev, Alexey A. and Cesarman, Ethel and Melnick, Ari M.},
date = {2021-01},
journaltitle = {Nature},
shortjournal = {Nature},
volume = {589},
number = {7841},
eprint = {33299181},
eprinttype = {pmid},
pages = {299--305},
issn = {1476-4687},
doi = {10.1038/s41586-020-3017-y},
abstract = {Linker histone H1 proteins bind to nucleosomes and facilitate chromatin compaction1, although their biological functions are poorly understood. Mutations in the genes that encode H1 isoforms B-E (H1B, H1C, H1D and H1E; also known as H1-5, H1-2, H1-3 and H1-4, respectively) are highly recurrent in B~cell lymphomas, but the pathogenic relevance of these mutations to cancer and the mechanisms that are involved are unknown. Here we show that lymphoma-associated H1 alleles are genetic driver mutations in lymphomas. Disruption of H1 function results in a profound architectural remodelling of the genome, which is characterized by large-scale yet focal shifts of chromatin from a compacted to a relaxed state. This decompaction drives distinct changes in epigenetic states, primarily owing to a gain of histone H3 dimethylation at lysine 36 (H3K36me2) and/or loss of repressive H3 trimethylation at lysine 27 (H3K27me3). These changes unlock the expression of stem cell genes that are normally silenced during early development. In mice, loss of H1c and H1e (also known as H1f2 and H1f4, respectively) conferred germinal centre B~cells with enhanced fitness and self-renewal properties, ultimately leading to aggressive lymphomas with an increased repopulating potential. Collectively, our data indicate that H1 proteins are normally required to sequester early developmental genes into architecturally inaccessible genomic compartments. We also establish H1 as a bona fide tumour suppressor and show that mutations in H1 drive malignant transformation primarily through three-dimensional genome reorganization, which leads to epigenetic reprogramming and derepression of developmentally silenced genes.},
langid = {english},
pmcid = {PMC7855728},
keywords = {Alleles,Animals,B-Lymphocytes,Cell Self Renewal,Cell Transformation Neoplastic,Chromatin,Chromatin Assembly and Disassembly,Epigenesis Genetic,Gene Expression Regulation Neoplastic,Gene Silencing,Genes Tumor Suppressor,Germinal Center,Histones,Humans,Lymphoma,Mice,Mutation,Stem Cells},
file = {/Users/rmorin/Zotero/storage/GE6IPBBF/Yusufova et al. - 2021 - Histone H1 loss drives lymphoma by disrupting 3D c.pdf}
}
@article{hodsonRegulationNormalBcell2016,
title = {Regulation of Normal {{B-cell}} Differentiation and Malignant {{B-cell}} Survival by {{OCT2}}},
author = {Hodson, Daniel J. and Shaffer, Arthur L. and Xiao, Wenming and Wright, George W. and Schmitz, Roland and Phelan, James D. and Yang, Yandan and Webster, Daniel E. and Rui, Lixin and Kohlhammer, Holger and Nakagawa, Masao and Waldmann, Thomas A. and Staudt, Louis M.},
date = {2016-04-05},
journaltitle = {Proceedings of the National Academy of Sciences of the United States of America},
shortjournal = {Proc Natl Acad Sci U S A},
volume = {113},
number = {14},
eprint = {26993806},
eprinttype = {pmid},
pages = {E2039-2046},
issn = {1091-6490},
doi = {10.1073/pnas.1600557113},
abstract = {The requirement for the B-cell transcription factor OCT2 (octamer-binding protein 2, encoded by Pou2f2) in germinal center B cells has proved controversial. Here, we report that germinal center B cells are formed normally after depletion of OCT2 in a conditional knockout mouse, but their proliferation is reduced and in vivo differentiation to antibody-secreting plasma cells is blocked. This finding led us to examine the role of OCT2 in germinal center-derived lymphomas. shRNA knockdown showed that almost all diffuse large B-cell lymphoma (DLBCL) cell lines are addicted to the expression of OCT2 and its coactivator OCA-B. Genome-wide chromatin immunoprecipitation (ChIP) analysis and gene-expression profiling revealed the broad transcriptional program regulated by OCT2 that includes the expression of STAT3, IL-10, ELL2, XBP1, MYC, TERT, and ADA. Importantly, genetic alteration of OCT2 is not a requirement for cellular addiction in DLBCL. However, we detected amplifications of the POU2F2 locus in DLBCL tumor biopsies and a recurrent mutation of threonine 223 in the DNA-binding domain of OCT2. This neomorphic mutation subtly alters the DNA-binding preference of OCT2, leading to the transactivation of noncanonical target genes including HIF1a and FCRL3 Finally, by introducing mutations designed to disrupt the OCT2-OCA-B interface, we reveal a requirement for this protein-protein interface that ultimately might be exploited therapeutically. Our findings, combined with the predominantly B-cell-restricted expression of OCT2 and the absence of a systemic phenotype in our knockout mice, suggest that an OCT2-targeted therapeutic strategy would be efficacious in both major subtypes of DLBCL while avoiding systemic toxicity.},
langid = {english},
pmcid = {PMC4833274},
keywords = {Animals,B-Lymphocytes,cancer biology,Cell Differentiation,Cell Line Tumor,Cell Survival,germinal center,lymphoma,Lymphoma Large B-Cell Diffuse,Mice,Mice Knockout,Organic Cation Transport Proteins,Organic Cation Transporter 2}
}
@article{melznerBiallelicMutationSOCS12005,
title = {Biallelic Mutation of {{SOCS-1}} Impairs {{JAK2}} Degradation and Sustains Phospho-{{JAK2}} Action in the {{MedB-1}} Mediastinal Lymphoma Line},
author = {Melzner, Ingo and Bucur, Alexandra Juliana and Brüderlein, Silke and Dorsch, Karola and Hasel, Cornelia and Barth, Thomas F. E. and Leithäuser, Frank and Möller, Peter},
date = {2005-03-15},
journaltitle = {Blood},
shortjournal = {Blood},
volume = {105},
number = {6},
eprint = {15572583},
eprinttype = {pmid},
pages = {2535--2542},
issn = {0006-4971},
doi = {10.1182/blood-2004-09-3701},
abstract = {Primary mediastinal B-cell lymphoma (PMBL) is a well-defined subtype of diffuse large B-cell lymphoma. Molecular cytogenetics revealed frequent gains of 9p24. JAK2, mapping in this region, is presently regarded as a candidate oncogene because expression profiling showed high Janus kinase-2 (JAK2) transcript levels and JAK2 was found to be constitutively phosphorylated in mediastinal B-cell lymphomas. We confirm that in the MedB-1 mediastinal B-cell line, harboring a trisomy 9, JAK2 transcription is elevated and the product is highly phosphorylated. However, JAK2 is not overexpressed at the protein level. On top, JAK2 protein turnover is even delayed. This unexpected finding coincides with a biallelic mutation of the suppressor of cytokine signaling-1 (SOCS-1) gene in this cell, which abrogates SOCS box function of the protein. Ectopic expression of wild-type (wt) SOCS-1 in MedB-1 leads to growth arrest and dramatic reduction of phospho-JAK2 and its downstream partner phospho-signal transducer and activator of transcription-5 (phospho-STAT5). Ultimately, the target gene cyclin D1 is repressed in transfectants while RB1, which is silenced in MedB-1, is induced. We conclude that, in MedB-1, action of phospho-JAK2 is sustained due to defective SOCS-1. Hence, SOCS-1 qualifies as a novel tumor suppressor. Of note, SOCS-1 mutations are also present in the parental tumor of MedB-1 and were detected in 9 of 20 PMBLs.},
langid = {english},
keywords = {Alleles,Cell Line Tumor,Chromosomes Human Pair 9,Cyclin D1,Gene Expression Regulation Leukemic,Humans,Intracellular Signaling Peptides and Proteins,Janus Kinase 2,Lymphoma B-Cell,Mediastinal Neoplasms,Mutation,Phosphorylation,Protein Processing Post-Translational,Protein-Tyrosine Kinases,Proto-Oncogene Proteins,Repressor Proteins,Retinoblastoma Protein,Signal Transduction,STAT5 Transcription Factor,Suppressor of Cytokine Signaling 1 Protein,Suppressor of Cytokine Signaling Proteins,Trisomy,Tumor Suppressor Proteins}
}
@article{hakemCaspase8EssentialMaintaining2012,
title = {Caspase-8 Is Essential for Maintaining Chromosomal Stability and Suppressing {{B-cell}} Lymphomagenesis},
author = {Hakem, Anne and El Ghamrasni, Samah and Maire, Georges and Lemmers, Benedicte and Karaskova, Jana and Jurisicova, Andrea and Sanchez, Otto and Squire, Jeremy and Hakem, Razqallah},
date = {2012-04-12},
journaltitle = {Blood},
shortjournal = {Blood},
volume = {119},
number = {15},
eprint = {22343728},
eprinttype = {pmid},
pages = {3495--3502},
issn = {1528-0020},
doi = {10.1182/blood-2011-07-367532},
abstract = {In addition to its proapoptotic function, caspase-8 is also important for several other processes, including suppressing necroptosis, cell migration, and immune cell survival. In the present study, we report that the loss of caspase-8 in B lymphocytes leads to B-cell malignancies and that the risk for these tumors is further enhanced in the absence of p53. We also report that deficiency of caspase-8 results in impaired cytokinesis and that casp8(-/-) lymphomas display remarkably elevated levels of chromosomal aberrations. Our data support an important role for caspase-8 in the maintenance of genomic integrity and highlight its tumor-suppressive function.},
langid = {english},
keywords = {3T3 Cells,Animals,Autoimmune Lymphoproliferative Syndrome,B-Lymphocytes,Caspase 8,Cells Cultured,Chromosomal Instability,Down-Regulation,Genes p53,Genetic Predisposition to Disease,Lymphoma B-Cell,Mice,Mice Inbred C57BL,Mice Transgenic,Survival Analysis}
}
@article{venturuttiTBL1XR1MutationsDrive2020,
title = {{{TBL1XR1 Mutations Drive Extranodal Lymphoma}} by {{Inducing}} a {{Pro-tumorigenic Memory Fate}}},
author = {Venturutti, Leandro and Teater, Matt and Zhai, Andrew and Chadburn, Amy and Babiker, Leena and Kim, Daleum and Béguelin, Wendy and Lee, Tak C. and Kim, Youngjun and Chin, Christopher R. and Yewdell, William T. and Raught, Brian and Phillip, Jude M. and Jiang, Yanwen and Staudt, Louis M. and Green, Michael R. and Chaudhuri, Jayanta and Elemento, Olivier and Farinha, Pedro and Weng, Andrew P. and Nissen, Michael D. and Steidl, Christian and Morin, Ryan D. and Scott, David W. and Privé, Gilbert G. and Melnick, Ari M.},
date = {2020-07-23},
journaltitle = {Cell},
shortjournal = {Cell},
volume = {182},
number = {2},
eprint = {32619424},
eprinttype = {pmid},
pages = {297-316.e27},
issn = {1097-4172},
doi = {10.1016/j.cell.2020.05.049},
abstract = {The most aggressive B cell lymphomas frequently manifest extranodal distribution and carry somatic mutations in the poorly characterized gene TBL1XR1. Here, we show that TBL1XR1 mutations skew the humoral immune response toward generating abnormal immature memory B cells (MB), while impairing plasma cell differentiation. At the molecular level, TBL1XR1 mutants co-opt SMRT/HDAC3 repressor complexes toward binding the MB cell transcription factor (TF) BACH2 at the expense of the germinal center (GC) TF BCL6, leading to pre-memory transcriptional reprogramming and cell-fate bias. Upon antigen recall, TBL1XR1 mutant MB cells fail to differentiate into plasma cells and instead preferentially reenter new GC reactions, providing evidence for a cyclic reentry lymphomagenesis mechanism. Ultimately, TBL1XR1 alterations lead to a striking extranodal immunoblastic lymphoma phenotype that mimics the human disease. Both human and murine lymphomas feature expanded MB-like cell populations, consistent with a MB-cell origin and delineating an unforeseen pathway for malignant transformation of the immune system.},
langid = {english},
pmcid = {PMC7384961},
keywords = {ABC-DLBCL,Animals,BACH2,Basic-Leucine Zipper Transcription Factors,BCL6,cell fate,cell of origin,Chromatin,extranodal lymphoma,germinal center,Germinal Center,Histone Deacetylases,Humans,Immunologic Memory,Lymphoma Large B-Cell Diffuse,memory B cells,Mice,Mice Inbred C57BL,Mice Knockout,Mutagenesis Site-Directed,Nuclear Proteins,Nuclear Receptor Co-Repressor 2,Precursor Cells B-Lymphoid,Protein Binding,Proto-Oncogene Proteins c-bcl-6,Receptors Cytoplasmic and Nuclear,Repressor Proteins,RNA Interference,RNA Small Interfering,TBL1XR1,Transcription Genetic}
}
@article{huNovelMissenseM206K2013,
title = {A Novel Missense ({{M206K}}) {{STAT3}} Mutation in Diffuse Large {{B}} Cell Lymphoma Deregulates {{STAT3}} Signaling},
author = {Hu, Guangzhen and Witzig, Thomas E. and Gupta, Mamta},
date = {2013},
journaltitle = {PloS One},
shortjournal = {PLoS One},
volume = {8},
number = {7},
eprint = {23861822},
eprinttype = {pmid},
pages = {e67851},
issn = {1932-6203},
doi = {10.1371/journal.pone.0067851},
abstract = {Persistent STAT3 activation has been found in activated B-cell like diffuse large B cell tumors (DLBCL). To investigate whether genetic mutations play a role in aberrant STAT3 signaling in DLBCL, we bi-directionally sequenced all 24 exons of the STAT3 gene in DLBCL tumors (n{$\mkern1mu$}={$\mkern1mu$}40). We identified 2 novel point mutations in 2 separate (2/40; 5\%) patients at exon 7 and 24. Point mutation 2552G{$>$}A was a silent mutation in the stop codon. Another heterozygous mutation 857T{$>$}A encoded a methionine substitution by lysine at codon 206 (M206K) in the coiled-coil domain of STAT3. We performed site directed mutagenesis to mutate wild type (WT) STAT3α and STAT3β at codon 206 and constructed stable cell lines by lentiviral transfection of STAT3α(WT), STAT3α(M206K), STAT3β(WT) and STAT3β(M206K) plasmids. The mutation was found to increase STAT3 phosphorylation in STAT3α mutant cell lines with no effect on the STAT3β mutant cell line. Transcriptional activation was also increased in the STAT3α mutant cells compared with STAT3α WT cells as detected by a luciferase reporter assay. Moreover, STAT3α(M206K) mutant cells were resistant to JAK2 pathway inhibition compared to STAT3α WT cells. These results indicate that missense mutations in STAT3 increase signaling through the JAK/STAT pathway. JAK2 inhibitors may be useful in the patient with this STAT3 mutation as well as those with pathway activation by other mechanisms.},
langid = {english},
pmcid = {PMC3701620},
keywords = {Amino Acid Sequence,B-Lymphocytes,Cell Line Tumor,Exons,Genes Reporter,Genetic Vectors,Humans,Janus Kinase 2,Lentivirus,Luciferases,Lymphoma Large B-Cell Diffuse,Molecular Sequence Data,Mutation Missense,Protein Isoforms,Protein Kinase Inhibitors,Sequence Alignment,Sequence Analysis DNA,Sequence Homology Amino Acid,Signal Transduction,STAT3 Transcription Factor,Transcriptional Activation}
}
@article{floriHematopoieticOncoproteinFOXP12016,
title = {The Hematopoietic Oncoprotein {{FOXP1}} Promotes Tumor Cell Survival in Diffuse Large {{B-cell}} Lymphoma by Repressing {{S1PR2}} Signaling},
author = {Flori, Michael and Schmid, Corina A. and Sumrall, Eric T. and Tzankov, Alexandar and Law, Charity W. and Robinson, Mark D. and Müller, Anne},
date = {2016-03-17},
journaltitle = {Blood},
shortjournal = {Blood},
volume = {127},
number = {11},
eprint = {26729899},
eprinttype = {pmid},
pages = {1438--1448},
issn = {1528-0020},
doi = {10.1182/blood-2015-08-662635},
abstract = {Aberrant expression of the oncogenic transcription factor forkhead box protein 1 (FOXP1) is a common feature of diffuse large B-cell lymphoma (DLBCL). We have combined chromatin immunoprecipitation and gene expression profiling after FOXP1 depletion with functional screening to identify targets of FOXP1 contributing to tumor cell survival. We find that the sphingosine-1-phosphate receptor 2 (S1PR2) is repressed by FOXP1 in activated B-cell (ABC) and germinal center B-cell (GCB) DLBCL cell lines with aberrantly high FOXP1 levels; S1PR2 expression is further inversely correlated with FOXP1 expression in 3 patient cohorts. Ectopic expression of wild-type S1PR2, but not a point mutant incapable of activating downstream signaling pathways, induces apoptosis in DLBCL cells and restricts tumor growth in subcutaneous and orthotopic models of the disease. The proapoptotic effects of S1PR2 are phenocopied by ectopic expression of the small G protein Gα13 but are independent of AKT signaling. We further show that low S1PR2 expression is a strong negative prognosticator of patient survival, alone and especially in combination with high FOXP1 expression. The S1PR2 locus has previously been demonstrated to be recurrently mutated in GCB DLBCL; the transcriptional silencing of S1PR2 by FOXP1 represents an alternative mechanism leading to inactivation of this important hematopoietic tumor suppressor.},
langid = {english},
keywords = {Animals,Apoptosis,Cell Line Tumor,Chromatin Immunoprecipitation,Forkhead Transcription Factors,Gene Expression Profiling,Gene Expression Regulation Neoplastic,Germinal Center,GTP-Binding Protein alpha Subunits G12-G13,Heterografts,Humans,Kaplan-Meier Estimate,Lymphoma Large B-Cell Diffuse,Mice,Neoplasm Proteins,Neoplasm Transplantation,Prognosis,Proto-Oncogene Proteins c-akt,Receptors Lysosphingolipid,Repressor Proteins,RNA Interference,RNA Small Interfering,Signal Transduction,Sphingosine-1-Phosphate Receptors}
}
@article{ortega-molinaOncogenicRagGTPase2019,
title = {Oncogenic {{Rag GTPase}} Signaling Enhances {{B}} Cell Activation and Drives Follicular Lymphoma Sensitive to Pharmacological Inhibition of {{mTOR}}},
author = {Ortega-Molina, Ana and Deleyto-Seldas, Nerea and Carreras, Joaquim and Sanz, Alba and Lebrero-Fernández, Cristina and Menéndez, Camino and Vandenberg, Andrew and Fernández-Ruiz, Beatriz and Marín-Arraiza, Leyre and family=Calle Arregui, given=Celia, prefix=de la, useprefix=true and Belén Plata-Gómez, Ana and Caleiras, Eduardo and family=Martino, given=Alba, prefix=de, useprefix=true and Martínez-Martín, Nuria and Troulé, Kevin and Piñeiro-Yáñez, Elena and Nakamura, Naoya and Araf, Shamzah and Victora, Gabriel D. and Okosun, Jessica and Fitzgibbon, Jude and Efeyan, Alejo},
date = {2019-08},
journaltitle = {Nature Metabolism},
shortjournal = {Nat Metab},
volume = {1},
number = {8},
eprint = {31579886},
eprinttype = {pmid},
pages = {775--789},
issn = {2522-5812},
doi = {10.1038/s42255-019-0098-8},
abstract = {The humoral immune response demands that B cells undergo a sudden anabolic shift and high cellular nutrient levels which are required to sustain the subsequent proliferative burst. Follicular lymphoma (FL) originates from B cells that have participated in the humoral response, and 15\% of FL samples harbor point, activating mutations in RRAGC, an essential activator of mTORC1 downstream of the sensing of cellular nutrients. The impact of recurrent RRAGC mutations in B cell function and lymphoma is unexplored. RRAGC mutations, targeted to the endogenous locus in mice, confer a partial insensitivity to nutrient deprivation, but strongly exacerbate B cell responses and accelerate lymphomagenesis, while creating a selective vulnerability to pharmacological inhibition of mTORC1. This moderate increase in nutrient signaling synergizes with paracrine cues from the supportive T cell microenvironment that activates B cells via the PI3K-Akt-mTORC1 axis. Hence, Rragc mutations sustain induced germinal centers and murine and human FL in the presence of decreased T cell help. Our results support a model in which activating mutations in the nutrient signaling pathway foster lymphomagenesis by corrupting a nutrient-dependent control over paracrine signals from the T cell microenvironment.},
langid = {english},
pmcid = {PMC6774795},
keywords = {Animals,apoptosis,B cell lymphoma,B lymphocytes,cell growth,germinal center,GTP Phosphohydrolases,Humans,Lymphocyte Activation,Lymphoma Follicular,Mice,Mice Transgenic,mTOR,nutrient signaling,rapamycin,RRAGC,Signal Transduction,T follicular helper,TOR Serine-Threonine Kinases}
}
@article{thomasMutationalAnalysisIkappaBalpha2004,
title = {Mutational Analysis of the {{IkappaBalpha}} Gene in Activated {{B}} Cell-like Diffuse Large {{B-cell}} Lymphoma},
author = {Thomas, Roman K. and Wickenhauser, Claudia and Tawadros, Samir and Diehl, Volker and Küppers, Ralf and Wolf, Jürgen and Schmitz, Roland},
date = {2004-07},
journaltitle = {British Journal of Haematology},
shortjournal = {Br J Haematol},
volume = {126},
number = {1},
eprint = {15198731},
eprinttype = {pmid},
pages = {50--54},
issn = {0007-1048},
doi = {10.1111/j.1365-2141.2004.05000.x},
abstract = {The lymphoma cells of the activated B cell-like (ABC-) subtype of diffuse large B-cell lymphoma (DLBCL) show constitutive activity of the transcription factor, nuclear factor kappaB (NFkappaB). We sought to determine whether mutations in the IkappaBalpha gene - the predominant inhibitor of NFkappaB - might play a role in the pathogenesis of ABC-DLBCL. All exons of the IkappaBalpha gene were directly sequenced from 10 cases of immunohistochemically classified ABC-DLBCL and from six non-ABC-DLBCL cases. Two novel polymorphisms were identified, based on their presence in tumour as well as non-tumour DNA of the respective patients: a duplication near the transcriptional start and a single nucleotide exchange in exon 1. A somatic missense mutation was identified in exon 3, in addition to a wild-type sequence in only one ABC-DLBCL case. Thus, also in this case no clonal biallelic inactivating mutation was present in the IkappaBalpha gene. We conclude that mutations in the IkappaBalpha gene do not play a dominant role in the pathogenesis of ABC-DLBCL.},
langid = {english},
keywords = {DNA Mutational Analysis,Humans,I-kappa B Proteins,Immunophenotyping,Lymphoma B-Cell,Lymphoma Large B-Cell Diffuse,NF-KappaB Inhibitor alpha,Polymorphism Genetic}
}
@article{qiuIRF8mutantCellLymphoma2024,
title = {{{IRF8-mutant B}} Cell Lymphoma Evades Immunity through a {{CD74-dependent}} Deregulation of Antigen Processing and Presentation in {{MHCII}} Complexes},
author = {Qiu, Zhijun and Khalife, Jihane and Ethiraj, Purushoth and Jaafar, Carine and Lin, An-Ping and Holder, Kenneth N. and Ritter, Jacob P. and Chiou, Lilly and Huelgas-Morales, Gabriela and Aslam, Sadia and Zhang, Zhao and Liu, Zhijie and Arya, Shailee and Gupta, Yogesh K. and Dahia, Patricia L. M. and Aguiar, Ricardo C. T.},
date = {2024-07-12},
journaltitle = {Science Advances},
shortjournal = {Sci Adv},
volume = {10},
number = {28},
eprint = {38996030},
eprinttype = {pmid},
pages = {eadk2091},
issn = {2375-2548},
doi = {10.1126/sciadv.adk2091},
abstract = {The mechanism by which interferon regulatory factor 8 (IRF8) mutation contributes to lymphomagenesis is unknown. We modeled IRF8 variants in B cell lymphomas and found that they affected the expression of regulators of antigen presentation. Expression of IRF8 mutants in murine B cell lymphomas suppressed CD4, but not CD8, activation elicited by antigen presentation and downmodulated CD74 and human leukocyte antigen (HLA) DM, intracellular regulators of antigen peptide processing/loading in the major histocompatibility complex (MHC) II. Concordantly, mutant IRF8 bound less efficiently to the promoters of these genes. Mice harboring IRF8 mutant lymphomas displayed higher tumor burden and remodeling of the tumor microenvironment, typified by depletion of CD4, CD8, and natural killer cells, increase in regulatory T cells and T follicular helper cells. Deconvolution of bulk RNA sequencing data from IRF8-mutant human diffuse large B cell lymphoma (DLBCL) recapitulated part of the immune remodeling detected in mice. We concluded that IRF8 mutations contribute to DLBCL biology by facilitating immune escape.},
langid = {english},
pmcid = {PMC11244530},
keywords = {Animals,Antigen Presentation,Antigens Differentiation B-Lymphocyte,Cell Line Tumor,Gene Expression Regulation Neoplastic,Histocompatibility Antigens Class II,Humans,Interferon Regulatory Factors,Lymphoma B-Cell,Lymphoma Large B-Cell Diffuse,Mice,Mutation,Tumor Escape,Tumor Microenvironment}
}
@article{guoSGK1MutationStatus2022b,
title = {{{SGK1}} Mutation Status Can Further Stratify Patients with Germinal Center {{B-cell-like}} Diffuse Large {{B-cell}} Lymphoma into Different Prognostic Subgroups},
author = {Guo, Baoping and Huang, Yujie and Duan, Ying and Liao, Chengcheng and Cen, Hong},
date = {2022-03},
journaltitle = {Cancer Medicine},
shortjournal = {Cancer Med},
volume = {11},
number = {5},
eprint = {35106936},
eprinttype = {pmid},
pages = {1281--1291},
issn = {2045-7634},
doi = {10.1002/cam4.4550},
abstract = {There are over a 100 driver gene mutations in patients with diffuse large B-cell lymphoma (DLBCL), but their clinical significance remains unclear. Here, we first analyzed the DLBCL dataset from the UK-based Haematological Malignancy Research Network. Patients were divided into high- and low-risk groups based on whether lymphoma progressed within 24~months. Genes showing significantly different frequencies between groups were selected. Survival data for patients with the selected mutant genes were analyzed. The results were validated using two other large databases to evaluate the relationship between the selected mutant genes and prognosis. The mutation frequencies of 11 genes (MYD88[L265P], SGK1, MPEG1, TP53, SPEN, NOTCH1, ETV6, TNFRSF14, MGA, CIITA, and PIM1) significantly differed between the high- and low-risk groups. The relationships between these mutant genes and patient survival were analyzed. Patients who harbored SGK1 (serum and glucocorticoid-inducible kinase 1) mutations exhibited the best prognosis. Most patients with SGK1 mutation are germinal center B-cell (GCB) subtype. Among patients with GCB DLBCL, those harboring SGK1 mutations exhibited better prognosis than those without SGK1 mutations. Most SGK1 mutations were single-base substitutions, primarily scattered throughout the catalytic domain-encoding region. Multiple SGK1 mutations were identified in a single patient. Thus, SGK1 mutations are a marker of good prognosis for DLBCL and occur predominantly in the GCB subtype of DLBCL. SGK1 mutation status can further stratify patients with GCB DLBCL into different prognostic subgroups.},
langid = {english},
pmcid = {PMC8894717},
keywords = {B-Lymphocytes,classification,diffuse large B-cell lymphoma,genetics,Germinal Center,Humans,Immediate-Early Proteins,Lymphoma Large B-Cell Diffuse,Mutation,prognosis,Prognosis,Protein Serine-Threonine Kinases,SGK1}
}
@article{jingjingNovelMEF2CMutation2020,
title = {A Novel {{MEF2C}} Mutation in Lymphoid Neoplasm Diffuse Large {{B-cell}} Lymphoma Promotes Tumorigenesis by Increasing c-{{JUN}} Expression},
author = {Jingjing, Zhao and Lei, Miao and Jie, Zhang and Sha, Cao and Yapeng, Hu and Weimin, Zhang and Chunluan, Yuan},
date = {2020-08},
journaltitle = {Naunyn-Schmiedeberg's Archives of Pharmacology},
shortjournal = {Naunyn Schmiedebergs Arch Pharmacol},
volume = {393},
number = {8},
eprint = {31900516},
eprinttype = {pmid},
pages = {1549--1558},
issn = {1432-1912},
doi = {10.1007/s00210-019-01764-6},
abstract = {Diffuse large B-cell lymphoma (DLBCL) is the most aggressive non-Hodgkin lymphoma (NHL), accounting for about 31\% of the newly diagnosed NHL worldwide. Although approximately 60\% of patients who initially received a standard R-CHOP treatment likely have a 3-year event-free survival, many patients become refractory or relapsed due to the genetic heterogeneity of this malignancy. Hence, new treatment strategies are urgently needed. MEF2C, a member of the MEF2 transcription factor family gene, plays great important roles involved in the development of various tissues and the pathogenesis of lymphoma. However, the exact functions and molecular mechanisms of MEF2C in DLBCL are not fully investigated. By Sanger sequencing, we identified a novel point mutation of MEF2C at the p.N389 site in DLBCL patient, which was further validated by several DLBCL cell lines. Intriguingly, we found that the p.N389S mutation did not influence MEF2C expression, protein stability, and subcellular distribution, but enhanced its transcriptional activity. Furthermore, we demonstrated that MEF2C p.N389S mutation promotes DLBCL cell proliferation, cellular adhesion, and tumor formation in nude mice. On mechanism, our data revealed that MEF2C p.N389S mutation increases c-JUN expression, and c-JUN regulation mediated the oncogenic function of MEF2C p.N389S mutation on DLBCL cells. Our finding may provide a significant insight into the DLBCL and a compelling therapy target for this disease treatment.},
langid = {english},
keywords = {Animals,c-JUN,Cell Adhesion,Cell Proliferation,Diffuse large B-cell lymphoma,Gene Expression Regulation Neoplastic,HEK293 Cells,Humans,Lymphoma Large B-Cell Diffuse,MEF2 Transcription Factors,MEF2C,Mice Nude,Mutation,Proto-Oncogene Proteins c-jun,Signal Transduction,Tumor Burden,Tumorigenesis,Up-Regulation}
}
@article{ohayreInactivatingMutationsGNA132016,
title = {Inactivating Mutations in {{GNA13}} and {{RHOA}} in {{Burkitt}}'s Lymphoma and Diffuse Large {{B-cell}} Lymphoma: A Tumor Suppressor Function for the {{Gα13}}/{{RhoA}} Axis in {{B}} Cells},
shorttitle = {Inactivating Mutations in {{GNA13}} and {{RHOA}} in {{Burkitt}}'s Lymphoma and Diffuse Large {{B-cell}} Lymphoma},
author = {O'Hayre, M. and Inoue, A. and Kufareva, I. and Wang, Z. and Mikelis, C. M. and Drummond, R. A. and Avino, S. and Finkel, K. and Kalim, K. W. and DiPasquale, G. and Guo, F. and Aoki, J. and Zheng, Y. and Lionakis, M. S. and Molinolo, A. A. and Gutkind, J. S.},
date = {2016-07-21},
journaltitle = {Oncogene},
shortjournal = {Oncogene},
volume = {35},
number = {29},
eprint = {26616858},
eprinttype = {pmid},
pages = {3771--3780},
issn = {1476-5594},
doi = {10.1038/onc.2015.442},
abstract = {G proteins and their cognate G protein-coupled receptors (GPCRs) function as critical signal transduction molecules that regulate cell survival, proliferation, motility and differentiation. The aberrant expression and/or function of these molecules have been linked to the growth, progression and metastasis of various cancers. As such, the analysis of mutations in the genes encoding GPCRs, G proteins and their downstream targets provides important clues regarding how these signaling cascades contribute to malignancy. Recent genome-wide sequencing efforts have unveiled the presence of frequent mutations in GNA13, the gene encoding the G protein Gα13, in Burkitt's lymphoma and diffuse large B-cell lymphoma (DLBCL). We found that mutations in the downstream target of Gα13, RhoA, are also present in Burkitt's lymphoma and DLBCL. By multiple complementary approaches, we now show that that these cancer-specific GNA13 and RHOA mutations are inhibitory in nature, and that the expression of wild-type Gα13 in B-cell lymphoma cells with mutant GNA13 has limited impact in vitro but results in a remarkable growth inhibition in vivo. Thus, although Gα13 and RhoA activity has previously been linked to cellular transformation and metastatic potential of epithelial cancers, our findings support a tumor suppressive role for Gα13 and RhoA in Burkitt's lymphoma and DLBCL.},
langid = {english},
pmcid = {PMC4885800},
keywords = {Animals,B-Lymphocytes,Blotting Western,Burkitt Lymphoma,Cell Line Tumor,DNA Mutational Analysis,Dogs,GTP-Binding Protein alpha Subunits G12-G13,HEK293 Cells,Humans,Lymphoma Large B-Cell Diffuse,Madin Darby Canine Kidney Cells,Mice Inbred NOD,Mice Knockout,Mice SCID,Microscopy Confocal,Mutation,rhoA GTP-Binding Protein,Signal Transduction,Transplantation Heterologous,Tumor Suppressor Proteins}
}
@article{barisicARID1AOrchestratesSWI2024,
title = {{{ARID1A}} Orchestrates {{SWI}}/{{SNF-mediated}} Sequential Binding of Transcription Factors with {{ARID1A}} Loss Driving Pre-Memory {{B}} Cell Fate and Lymphomagenesis},
author = {Barisic, Darko and Chin, Christopher R. and Meydan, Cem and Teater, Matt and Tsialta, Ioanna and Mlynarczyk, Coraline and Chadburn, Amy and Wang, Xuehai and Sarkozy, Margot and Xia, Min and Carson, Sandra E. and Raggiri, Santo and Debek, Sonia and Pelzer, Benedikt and Durmaz, Ceyda and Deng, Qing and Lakra, Priya and Rivas, Martin and Steidl, Christian and Scott, David W. and Weng, Andrew P. and Mason, Christopher E. and Green, Michael R. and Melnick, Ari},
date = {2024-04-08},
journaltitle = {Cancer Cell},
shortjournal = {Cancer Cell},
volume = {42},
number = {4},
eprint = {38458187},
eprinttype = {pmid},
pages = {583-604.e11},
issn = {1878-3686},
doi = {10.1016/j.ccell.2024.02.010},
abstract = {ARID1A, a subunit of the canonical BAF nucleosome remodeling complex, is commonly mutated in lymphomas. We show that ARID1A orchestrates B cell fate during the germinal center (GC) response, facilitating cooperative and sequential binding of PU.1 and NF-kB at crucial genes for cytokine and CD40 signaling. The absence of ARID1A tilts GC cell fate toward immature IgM+CD80-PD-L2- memory B cells, known for their potential to re-enter new GCs. When combined with BCL2 oncogene, ARID1A haploinsufficiency hastens the progression of aggressive follicular lymphomas (FLs) in mice. Patients with FL with ARID1A-inactivating mutations preferentially display an immature memory B cell-like state with increased transformation risk to aggressive disease. These observations offer mechanistic understanding into the emergence of both indolent and aggressive ARID1A-mutant lymphomas through the formation of immature memory-like clonal precursors. Lastly, we demonstrate that ARID1A mutation induces synthetic lethality to SMARCA2/4 inhibition, paving the way for potential precision therapy for high-risk patients.},
langid = {english},
keywords = {Animals,BAF complex,chromatin,chromatin remodeling,clonal precursor cells,DNA-Binding Proteins,epigenetics,Humans,humoral immunity,lymphoma,Lymphoma,Memory B Cells,Mice,Mutation,Nuclear Proteins,pioneer transcription factors,plasticity,precision therapy,Transcription Factors}
}
@article{dobashiTP53OSBPL10Alterations2018,
title = {{{TP53}} and {{OSBPL10}} Alterations in Diffuse Large {{B-cell}} Lymphoma: Prognostic Markers Identified via Exome Analysis of Cases with Extreme Prognosis},
shorttitle = {{{TP53}} and {{OSBPL10}} Alterations in Diffuse Large {{B-cell}} Lymphoma},
author = {Dobashi, Akito and Togashi, Yuki and Tanaka, Norio and Yokoyama, Masahiro and Tsuyama, Naoko and Baba, Satoko and Mori, Seiichi and Hatake, Kiyohiko and Yamaguchi, Toshiharu and Noda, Tetsuo and Takeuchi, Kengo},
date = {2018-04-13},
journaltitle = {Oncotarget},
shortjournal = {Oncotarget},
volume = {9},
number = {28},
eprint = {29731965},
eprinttype = {pmid},
pages = {19555--19568},
issn = {1949-2553},
doi = {10.18632/oncotarget.24656},
abstract = {Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma subtype characterized by both biological and clinical heterogeneity. In refractory cases, complete response/complete response unconfirmed rates in salvage therapy remain low. We performed whole-exome sequencing of DLBCL in a discovery cohort comprising 26 good and nine poor prognosis cases. After candidate genes were identified, prognoses were examined in 85 individuals in the DLBCL validation cohort. In the discovery cohort, five patients in the poor prognosis group harbored both a TP53 mutation and 17p deletion. Sixteen mutations were identified in OSBPL10 in nine patients in the good prognosis group, but none in the poor prognosis group. In the validation cohort, TP53 mutations and TP53 deletions were confirmed to be poor prognostic factors for overall survival (OS) (P = 0.016) and progression-free survival (PFS) (P = 0.023) only when both aberrations co-existed. OSBPL10 mutations were validated as prognostic markers for excellent OS (P = 0.037) and PFS (P = 0.041). Significant differences in OS and PFS were observed when patients were stratified into three groups-OSBPL10 mutation (best prognosis), the coexistence of both TP53 mutation and TP53 deletion (poorest prognosis), and others. In this study, the presence of both TP53 mutation and 17p/TP53 deletion, but not the individual variants, was associated with poor prognosis in DLBCL patients after treatment with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) or similar regimens. We also identified OSBPL10 mutation as a marker for patients with excellent prognosis in the R-CHOP era.},
langid = {english},
pmcid = {PMC5929408},
keywords = {diffuse large B-cell lymphoma,next-generation sequencing,OSBPL10,prognostic marker,TP53}
}
@article{christieCMYCTranslocation142008,
title = {C-{{MYC}} Translocation in t(14;18) Positive Follicular Lymphoma at Presentation: {{An}} Adverse Prognostic Indicator?},
shorttitle = {C-{{MYC}} Translocation in t(14;18) Positive Follicular Lymphoma at Presentation},
author = {Christie, Lesley and Kernohan, Neil and Levison, David and Sales, Mark and Cunningham, Joan and Gillespie, Karen and Batstone, Paul and Meiklejohn, David and Goodlad, John},
date = {2008-03},
journaltitle = {Leukemia \& Lymphoma},
shortjournal = {Leuk Lymphoma},
volume = {49},
number = {3},
eprint = {18297523},
eprinttype = {pmid},
pages = {470--476},
issn = {1029-2403},
doi = {10.1080/10428190701836845},
abstract = {Follicular lymphoma (FL) is a common subtype of low grade B-cell non-Hodgkin lymphoma (NHL). Although this form of lymphoma often pursues an indolent course, in some cases it may behave in a more aggressive manner. Clinical and histological parameters have been shown to correlate with an adverse prognosis but a number of cytogenetic abnormalities may also be associated with aggressive disease. Although, the t(14;18) in itself does not affect outcome in cases of FL, secondary abnormalities that occur in a complex polyploid karyotype may identify cases with a poor prognosis. It is unusual to find both t(14;18) and C-MYC translocation in the same tumour; those cases in which it has been described include examples of high-grade B-cell NHL (either de novo or transformed FL) or B-cell acute lymphoblastic lymphoma. In this report, three cases of FL are described in which both t(14;18) and a C-MYC translocation were identified at presentation. We also summarize four further cases from the literature. This is a small series but one which raises the possibility that the presence of a C-MYC translocations at presentation may identify a particularly aggressive subtype of FL. Further studies are required to investigate the true incidence of this aberration, the impact on C-MYC regulation, clinical course and response to treatment.},
langid = {english},
keywords = {Aged,Chromosomes Human Pair 14,Chromosomes Human Pair 18,Chromosomes Human Pair 8,Cytogenetic Analysis,Female,Humans,Lymphoma Follicular,Male,Prognosis,Proto-Oncogene Proteins c-myc,Translocation Genetic,Treatment Outcome}
}
@article{giallongoIdentificationCmycOncogene1983,
title = {Identification of the C-Myc Oncogene Product in Normal and Malignant {{B}} Cells},
author = {Giallongo, A. and Appella, E. and Ricciardi, R. and Rovera, G. and Croce, C. M.},
date = {1983-10-28},
journaltitle = {Science (New York, N.Y.)},
shortjournal = {Science},
volume = {222},
number = {4622},
eprint = {6604943},
eprinttype = {pmid},
pages = {430--432},
issn = {0036-8075},
doi = {10.1126/science.6604943},
abstract = {Antiserum to a synthetic peptide corresponding to the carboxyl-terminus of the human c-myc protein immunoprecipitated a 48,000-dalton protein from a number of normal and malignant human and mouse cells. The size of the protein is consistent with the potential coding region predicted from the c-myc nucleotide sequence, and is the same for malignant cells carrying either a rearranged or an unrearranged c-myc oncogene. Because c-myc transcripts are expressed at higher levels in malignant than in normal B cells, it appears that an increased level of the c-myc protein rather than a change in the gene product is the relevant factor in determining transformation.},
langid = {english},
keywords = {B-Lymphocytes,Burkitt Lymphoma,Gene Expression Regulation,Humans,Oncogenes,Peptide Fragments,Proteins,Transformation Genetic}
}
@article{liLossCREBBPKMT2D2024,
title = {Loss of {{CREBBP}} and {{KMT2D}} Cooperate to Accelerate Lymphomagenesis and Shape the Lymphoma Immune Microenvironment},
author = {Li, Jie and Chin, Christopher R. and Ying, Hsia-Yuan and Meydan, Cem and Teater, Matthew R. and Xia, Min and Farinha, Pedro and Takata, Katsuyoshi and Chu, Chi-Shuen and Jiang, Yiyue and Eagles, Jenna and Passerini, Verena and Tang, Zhanyun and Rivas, Martin A. and Weigert, Oliver and Pugh, Trevor J. and Chadburn, Amy and Steidl, Christian and Scott, David W. and Roeder, Robert G. and Mason, Christopher E. and Zappasodi, Roberta and Béguelin, Wendy and Melnick, Ari M.},
date = {2024-04-03},
journaltitle = {Nature Communications},
shortjournal = {Nat Commun},
volume = {15},
number = {1},
eprint = {38570506},
eprinttype = {pmid},
pages = {2879},
issn = {2041-1723},
doi = {10.1038/s41467-024-47012-1},
abstract = {Despite regulating overlapping gene enhancers and pathways, CREBBP and KMT2D mutations recurrently co-occur in germinal center (GC) B cell-derived lymphomas, suggesting potential oncogenic cooperation. Herein, we report that combined haploinsufficiency of Crebbp and Kmt2d induces a more severe mouse lymphoma phenotype (vs either allele alone) and unexpectedly confers an immune evasive microenvironment manifesting as CD8+ T-cell exhaustion and reduced infiltration. This is linked to profound repression of immune synapse genes that mediate crosstalk with T-cells, resulting in aberrant GC B cell fate decisions. From the epigenetic perspective, we observe interaction and mutually dependent binding and function of CREBBP and KMT2D on chromatin. Their combined deficiency preferentially impairs activation of immune synapse-responsive super-enhancers, pointing to a particular dependency for both co-activators at these specialized regulatory elements. Together, our data provide an example where chromatin modifier mutations cooperatively shape and induce an immune-evasive microenvironment to facilitate lymphomagenesis.},
langid = {english},
pmcid = {PMC10991284},
keywords = {Animals,B-Lymphocytes,Chromatin,Germinal Center,Lymphoma Large B-Cell Diffuse,Mice,Mutation,Tumor Microenvironment}
}
@article{merirantaDisruptionKLHL6Fuels2024,
title = {Disruption of {{KLHL6 Fuels Oncogenic Antigen Receptor Signaling}} in {{B-cell Lymphoma}}},
author = {Meriranta, Leo and Sorri, Selma and Huse, Kanutte and Liu, Xiaonan and Spasevska, Ivana and Zafar, Sadia and Chowdhury, Iftekhar and Dufva, Olli and Sahlberg, Eerika and Tandaric, Luka and Karjalainen-Lindsberg, Marja-Liisa and Hyytiainen, Marko and Varjosalo, Markku and Myklebust, June H. and Leppa, Sirpa},
date = {2024-04-17},
journaltitle = {Blood Cancer Discovery},
shortjournal = {Blood Cancer Discov},
eprint = {38630892},
eprinttype = {pmid},
issn = {2643-3249},
doi = {10.1158/2643-3230.BCD-23-0182},
abstract = {Pathomechanisms that activate oncogenic B-cell receptor (BCR) signaling in diffuse large B-cell lymphoma (DLBCL), are largely unknown. Kelch-like family member 6 (KLHL6) encoding a substrate-adapter for Cullin-3-RING E3 ubiquitin-ligase (CRL) with poorly established targets is recurrently mutated in DLBCL. By applying high-throughput protein interactome screens and functional characterization, we discovered that KLHL6 regulates BCR by targeting its signaling subunits CD79A and CD79B. Loss of physiological KLHL6 expression pattern was frequent among the MCD/C5-like activated B-cell DLBCLs and was associated with higher CD79B levels and dismal outcome. Mutations in the BTB domain of KLHL6 disrupted its localization and heterodimerization, and increased surface BCR levels and signaling, whereas Kelch domain mutants had the opposite effect. Malfunctions of KLHL6 mutants extended beyond proximal BCR signaling with distinct phenotypes from KLHL6 silencing. Collectively, our findings uncover how recurrent mutations in KLHL6 alter BCR signaling and induce actionable phenotypic characteristics in DLBCL.},
langid = {english}
}
@article{choiRegulationCellReceptordependent2020,
title = {Regulation of {{B}} Cell Receptor-Dependent {{NF-κB}} Signaling by the Tumor Suppressor {{KLHL14}}},
author = {Choi, Jaewoo and Phelan, James D. and Wright, George W. and Häupl, Björn and Huang, Da Wei and Shaffer, Arthur L. and Young, Ryan M. and Wang, Zhuo and Zhao, Hong and Yu, Xin and Oellerich, Thomas and Staudt, Louis M.},
date = {2020-03-17},
journaltitle = {Proceedings of the National Academy of Sciences of the United States of America},
shortjournal = {Proc Natl Acad Sci U S A},
volume = {117},
number = {11},
eprint = {32127472},
eprinttype = {pmid},
pages = {6092--6102},
issn = {1091-6490},
doi = {10.1073/pnas.1921187117},
abstract = {The KLHL14 gene acquires frequent inactivating mutations in mature B cell malignancies, especially in the MYD88L265P, CD79B mutant (MCD) genetic subtype of diffuse large B cell lymphoma (DLBCL), which relies on B cell receptor (BCR) signaling for survival. However, the pathogenic role of KLHL14 in DLBCL and its molecular function are largely unknown. Here, we report that KLHL14 is in close proximity to the BCR in the endoplasmic reticulum of MCD cell line models and promotes the turnover of immature glycoforms of BCR subunits, reducing total cellular BCR levels. Loss of KLHL14 confers relative resistance to the Bruton tyrosine kinase (BTK) inhibitor ibrutinib and promotes assembly of the MYD88-TLR9-BCR (My-T-BCR) supercomplex, which initiates prosurvival NF-κB activation. Consequently, KLHL14 inactivation allows MCD cells to maintain NF-κB signaling in the presence of ibrutinib. These findings reinforce the central role of My-T-BCR-dependent NF-κB signaling in MCD DLBCL and suggest that the genetic status of KLHL14 should be considered in clinical trials testing inhibitors of BTK and BCR signaling mediators in DLBCL.},
langid = {english},
pmcid = {PMC7084139},
keywords = {Adenine,B cell receptor,Carrier Proteins,CD79 Antigens,Cell Line Tumor,DLBCL,Drug Resistance Neoplasm,Endoplasmic Reticulum,Genes Tumor Suppressor,HEK293 Cells,Humans,Intracellular Signaling Peptides and Proteins,KLHL14,Lymphoma Large B-Cell Diffuse,Mutagenesis Site-Directed,Myeloid Differentiation Factor 88,NF-kappa B,NF-κB,Piperidines,Proteolysis,Pyrazoles,Pyrimidines,Receptors Antigen B-Cell,Signal Transduction,Ubiquitin-Protein Ligase Complexes}
}
@article{hodkinsonBiomarkersResponseIbrutinib2021,
title = {Biomarkers of Response to Ibrutinib plus Nivolumab in Relapsed Diffuse Large {{B-cell}} Lymphoma, Follicular Lymphoma, or {{Richter}}'s Transformation},
author = {Hodkinson, Brendan P. and Schaffer, Michael and Brody, Joshua D. and Jurczak, Wojciech and Carpio, Cecilia and Ben-Yehuda, Dina and Avivi, Irit and Forslund, Ann and Özcan, Muhit and Alvarez, John and Ceulemans, Rob and Fourneau, Nele and Younes, Anas and Balasubramanian, Sriram},
date = {2021-01},
journaltitle = {Translational Oncology},
shortjournal = {Transl Oncol},
volume = {14},
number = {1},
eprint = {33395752},
eprinttype = {pmid},
pages = {100977},
issn = {1936-5233},
doi = {10.1016/j.tranon.2020.100977},
abstract = {We analyzed potential biomarkers of response to ibrutinib plus nivolumab in biopsies from patients with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and Richter's transformation (RT) from the LYM1002 phase I/IIa study, using programmed death ligand 1 (PD-L1) immunohistochemistry, whole exome sequencing (WES), and gene expression profiling (GEP). In DLBCL, PD-L1 elevation was more frequent in responders versus nonresponders (5/8 [62.5\%] vs. 3/16 [18.8\%]; p\,=\,0.065; complete response 37.5\% vs. 0\%; p\,=\,0.028). Overall response rates for patients with WES and GEP data, respectively, were: DLBCL (38.5\% and 29.6\%); FL (46.2\% and 43.5\%); RT (76.5\% and 81.3\%). In DLBCL, WES analyses demonstrated that mutations in RNF213 (40.0\% vs. 6.2\%; p\,=\,0.055), KLHL14 (30.0\% vs. 0\%; p\,=\,0.046), and LRP1B (30.0\% vs. 6.2\%; p\,=\,0.264) were more frequent in responders. No responders had mutations in EBF1, ADAMTS20, AKAP9, TP53, MYD88, or TNFRSF14, while the frequency of these mutations in nonresponders ranged from 12.5\% to 18.8\%. In FL and RT, genes with different mutation frequencies in responders versus nonresponders were: BCL2 (75.0\% vs. 28.6\%; p\,=\,0.047) and ROS1 (0\% vs. 50.0\%; p\,=\,0.044), respectively. Per GEP, the most upregulated genes in responders were LEF1 and BTLA (overall), and CRTAM (germinal center B-cell-like DLBCL). Enriched pathways were related to immune activation in responders and resistance-associated proliferation/replication in nonresponders. This preliminary work may help to generate hypotheses regarding genetically defined subsets of DLBCL, FL, and RT patients most likely to benefit from ibrutinib plus nivolumab.},
langid = {english},
pmcid = {PMC7723809},
keywords = {Biomarkers,Ibrutinib,Nivolumab,Non-hodgkin's lymphoma,Phase I/II trial}
}
@article{saffieFBXW7TriggersDegradation2020b,
title = {{{FBXW7 Triggers Degradation}} of {{KMT2D}} to {{Favor Growth}} of {{Diffuse Large B-cell Lymphoma Cells}}},
author = {Saffie, Rizwan and Zhou, Nan and Rolland, Delphine and Önder, Özlem and Basrur, Venkatesha and Campbell, Sydney and Wellen, Kathryn E. and Elenitoba-Johnson, Kojo S. J. and Capell, Brian C. and Busino, Luca},
date = {2020-06-15},
journaltitle = {Cancer Research},
shortjournal = {Cancer Res},
volume = {80},
number = {12},
eprint = {32350066},
eprinttype = {pmid},
pages = {2498--2511},
issn = {1538-7445},
doi = {10.1158/0008-5472.CAN-19-2247},
abstract = {Mature B-cell neoplasms are the fifth most common neoplasm. Due to significant heterogeneity at the clinical and genetic levels, current therapies for these cancers fail to provide long-term cures. The clinical success of proteasome inhibition for the treatment of multiple myeloma and B-cell lymphomas has made the ubiquitin pathway an important emerging therapeutic target. In this study, we assessed the role of the E3 ligase FBXW7 in mature B-cell neoplasms. FBXW7 targeted the frequently inactivated tumor suppressor KMT2D for protein degradation, subsequently regulating gene expression signatures related to oxidative phosphorylation (OxPhos). Loss of FBXW7 inhibited diffuse large B-cell lymphoma cell growth and further sensitized cells to OxPhos inhibition. These data elucidate a novel mechanism of regulation of KMT2D levels by the ubiquitin pathway and uncover a role of FBXW7 in regulating oxidative phosphorylation in B-cell malignancies. SIGNIFICANCE: These findings characterize FBXW7 as a prosurvival factor in B-cell lymphoma via degradation of the chromatin modifier KMT2D.},
langid = {english},
pmcid = {PMC7417195},
keywords = {Animals,Cell Line Tumor,Cell Proliferation,Chromatin,DNA-Binding Proteins,F-Box-WD Repeat-Containing Protein 7,Female,Gene Expression Regulation Neoplastic,Gene Knockout Techniques,HEK293 Cells,Humans,Lymphoma Large B-Cell Diffuse,Mice,Neoplasm Proteins,Oxidative Phosphorylation,Proteolysis,RNA Small Interfering,Signal Transduction,Ubiquitin,Xenograft Model Antitumor Assays}
}
@article{schneiderFBXO11InactivationLeads2016b,
title = {{{FBXO11}} Inactivation Leads to Abnormal Germinal-Center Formation and Lymphoproliferative Disease},
author = {Schneider, Christof and Kon, Ning and Amadori, Letizia and Shen, Qiong and Schwartz, Friederike H. and Tischler, Benjamin and Bossennec, Marion and Dominguez-Sola, David and Bhagat, Govind and Gu, Wei and Basso, Katia and Dalla-Favera, Riccardo},
date = {2016-08-04},
journaltitle = {Blood},
shortjournal = {Blood},
volume = {128},
number = {5},
eprint = {27166359},
eprinttype = {pmid},
pages = {660--666},
issn = {1528-0020},
doi = {10.1182/blood-2015-11-684357},
abstract = {The BCL6 proto-oncogene encodes a transcriptional repressor that is required for the germinal center (GC) reaction and is implicated in lymphomagenesis. BCL6 protein stability is regulated by F-box protein 11 (FBXO11)-mediated ubiquitination and degradation, which is impaired in ∼6\% of diffuse large B-cell lymphomas that carry inactivating genetic alterations targeting the FBXO11 gene. In order to investigate the role of FBXO11 in vivo, we analyzed GC-specific FBXO11 knockout mice. FBXO11 reduction or loss led to an increased number of GC B cells, to an altered ratio of GC dark zone to light zone cells, and to higher levels of BCL6 protein in GC B cells. B-cell receptor-mediated degradation of BCL6 was reduced in the absence of FBXO11, suggesting that FBXO11 contributes to the physiologic downregulation of BCL6 at the end of the GC reaction. Finally, FBXO11 inactivation was associated with the development of lymphoproliferative disorders in mice.},
langid = {english},
pmcid = {PMC9709922},
keywords = {Animals,B-Lymphocytes,Cell Line Tumor,Down-Regulation,F-Box Proteins,Gene Deletion,Gene Silencing,Gene Targeting,Germinal Center,Humans,Immunoglobulin M,Lymphocyte Count,Lymphoproliferative Disorders,Mice,Organ Specificity,Proto-Oncogene Mas,Proto-Oncogene Proteins c-bcl-6}
}
@article{seebergerLossFasCD952001,
title = {Loss of {{Fas}} ({{CD95}}/{{APO-1}}) Regulatory Function Is an Important Step in Early {{MALT-type}} Lymphoma Development},
author = {Seeberger, H. and Starostik, P. and Schwarz, S. and Knörr, C. and Kalla, J. and Ott, G. and Müller-Hermelink, H. K. and Greiner, A.},
date = {2001-07},
journaltitle = {Laboratory Investigation; a Journal of Technical Methods and Pathology},
shortjournal = {Lab Invest},
volume = {81},
number = {7},
eprint = {11454987},
eprinttype = {pmid},
pages = {977--986},
issn = {0023-6837},
doi = {10.1038/labinvest.3780310},
abstract = {Fas (CD95, APO-1) mutations were found in autoimmune diseases and some lymphomas, suggesting impairment of Fas-mediated cell death signaling that may cause tumor development. Because mucosa-associated lymphoid tissue (MALT)-type lymphoma B cells recognize autoantigens and proliferate in response to antigen and T cell-mediated signals, it is suggestive that autoreactive B cell lymphoma precursor cells may have escaped the Fas-mediated checkpoint that normally operates in healthy individuals. Using different biochemical, molecular, and functional approaches, we analyzed the Fas signaling in malignant B cells from seven MALT-type lymphomas that were additionally characterized for the t(11;18)(q21;q21) and four gastric diffuse large B cell lymphomas (DLBL). All DLBLs and three of seven MALT-type lymphomas were resistant to Fas-mediated apoptosis in vitro. Moreover, four of five MALT-type lymphomas analyzed and one of three DLBLs analyzed showed mutations in Fas mRNA transcripts but no loss of heterozygosity in the Fas promotor region. Alternative mechanisms of resistance to apoptosis, such as decreased expression of Fas or production of soluble Fas were not operative. Therefore, it is suggestive that a subgroup of MALT-type lymphoma B cells, irrespective of t(11;18)(q21;q21), escape the censoring Fas pathway by mutating and inactivating Fas. This identifies a key regulatory step in early MALT-type lymphomagenesis.},
langid = {english},
keywords = {Adult,Aged,Apoptosis,B-Lymphocytes,Base Sequence,Caspase 3,Caspase 8,Caspase 9,Caspases,DNA Primers,fas Receptor,Female,Humans,Loss of Heterozygosity,Lymphoma B-Cell Marginal Zone,Male,Middle Aged,Mutation,Promoter Regions Genetic,RNA Messenger,Sequence Homology Nucleic Acid}
}
@article{ennishiTMEM30ALossoffunctionMutations2020,
title = {{{TMEM30A}} Loss-of-Function Mutations Drive Lymphomagenesis and Confer Therapeutically Exploitable Vulnerability in {{B-cell}} Lymphoma},
author = {Ennishi, Daisuke and Healy, Shannon and Bashashati, Ali and Saberi, Saeed and Hother, Christoffer and Mottok, Anja and Chan, Fong Chun and Chong, Lauren and Abraham, Libin and Kridel, Robert and Boyle, Merrill and Meissner, Barbara and Aoki, Tomohiro and Takata, Katsuyoshi and Woolcock, Bruce W. and Viganò, Elena and Gold, Michael and Molday, Laurie L. and Molday, Robert S. and Telenius, Adele and Li, Michael Y. and Wretham, Nicole and Dos Santos, Nancy and Wong, Mark and Viller, Natasja N. and Uger, Robert A. and Duns, Gerben and Baticados, Abigail and Madero, Angel and Bristow, Brianna N. and Farinha, Pedro and Slack, Graham W. and Ben-Neriah, Susana and Lai, Daniel and Zhang, Allen W. and Salehi, Sohrab and Shulha, Hennady P. and Chiu, Derek S. and Mostafavi, Sara and Gerrie, Alina S. and Huang, Da Wei and Rushton, Christopher and Villa, Diego and Sehn, Laurie H. and Savage, Kerry J. and Mungall, Andrew J. and Weng, Andrew P. and Bally, Marcel B. and Morin, Ryan D. and Cohen Freue, Gabriela V. and Staudt, Louis M. and Connors, Joseph M. and Marra, Marco A. and Shah, Sohrab P. and Gascoyne, Randy D. and Scott, David W. and Steidl, Christian},
date = {2020-04},
journaltitle = {Nature Medicine},
shortjournal = {Nat Med},
volume = {26},
number = {4},
eprint = {32094924},
eprinttype = {pmid},
pages = {577--588},
issn = {1546-170X},
doi = {10.1038/s41591-020-0757-z},
abstract = {Transmembrane protein 30A (TMEM30A) maintains the asymmetric distribution of phosphatidylserine, an integral component of the cell membrane and 'eat-me' signal recognized by macrophages. Integrative genomic and transcriptomic analysis of diffuse large B-cell lymphoma (DLBCL) from the British Columbia population-based registry uncovered recurrent biallelic TMEM30A loss-of-function mutations, which were associated with a favorable outcome and uniquely observed in DLBCL. Using TMEM30A-knockout systems, increased accumulation of chemotherapy drugs was observed in TMEM30A-knockout cell lines and TMEM30A-mutated primary cells, explaining the improved treatment outcome. Furthermore, we found increased tumor-associated macrophages and an enhanced effect of anti-CD47 blockade limiting tumor growth in TMEM30A-knockout models. By contrast, we show that TMEM30A loss-of-function increases B-cell signaling following antigen stimulation-a mechanism conferring selective advantage during B-cell lymphoma development. Our data highlight a multifaceted role for TMEM30A in B-cell lymphomagenesis, and characterize intrinsic and extrinsic vulnerabilities of cancer cells that can be therapeutically exploited.},
langid = {english},
pmcid = {PMC8480332},
keywords = {Adolescent,Adult,Aged,Aged 80 and over,Animals,British Columbia,Cell Transformation Neoplastic,Cells Cultured,Cohort Studies,Female,Genetic Predisposition to Disease,HEK293 Cells,Humans,Jurkat Cells,Loss of Function Mutation,Lymphoma Large B-Cell Diffuse,Male,Membrane Proteins,Mice,Mice Inbred BALB C,Mice Inbred NOD,Mice SCID,Mice Transgenic,Middle Aged,Molecular Targeted Therapy,Young Adult}
}
@article{demirandaExomeSequencingReveals2014,
title = {Exome Sequencing Reveals Novel Mutation Targets in Diffuse Large {{B-cell}} Lymphomas Derived from {{Chinese}} Patients},
author = {family=Miranda, given=Noel F. C. C., prefix=de, useprefix=true and Georgiou, Konstantinos and Chen, Longyun and Wu, Chenglin and Gao, Zhibo and Zaravinos, Apostolos and Lisboa, Susana and Enblad, Gunilla and Teixeira, Manuel R. and Zeng, Yixin and Peng, Roujun and Pan-Hammarström, Qiang},
date = {2014-10-16},
journaltitle = {Blood},
shortjournal = {Blood},
volume = {124},
number = {16},
eprint = {25171927},
eprinttype = {pmid},
pages = {2544--2553},
issn = {1528-0020},
doi = {10.1182/blood-2013-12-546309},
abstract = {Next-generation sequencing studies on diffuse large B-cell lymphomas (DLBCLs) have revealed novel targets of genetic aberrations but also high intercohort heterogeneity. Previous studies have suggested that the prevalence of disease subgroups and cytogenetic profiles differ between Western and Asian patients. To characterize the coding genome of Chinese DLBCL, we performed whole-exome sequencing of DNA derived from 31 tumors and respective peripheral blood samples. The mutation prevalence of B2M, CD70, DTX1, LYN, TMSB4X, and UBE2A was investigated in an additional 105 tumor samples. We discovered 11 novel targets of recurrent mutations in DLBCL that included functionally relevant genes such as LYN and TMSB4X. Additional genes were found mutated at high frequency (≥10\%) in the Chinese cohort including DTX1, which was the most prevalent mutation target in the Notch pathway. We furthermore demonstrated that mutations in DTX1 impair its function as a negative regulator of Notch. Novel and previous unappreciated targets of somatic mutations in DLBCL identified in this study support the existence of additional/alternative tumorigenic pathways in these tumors. The observed differences with previous reports might be explained by the genetic heterogeneity of DLBCL, the germline genetic makeup of Chinese individuals, and/or exposure to distinct etiological agents.},
langid = {english},
pmcid = {PMC4199956},
keywords = {Asian People,China,Exome,Female,Genetic Heterogeneity,High-Throughput Nucleotide Sequencing,Humans,Lymphoma Large B-Cell Diffuse,Male,Middle Aged,Mutation,Receptors Notch,Signal Transduction,Ubiquitin-Protein Ligases}
}
@article{jardinDiffuseLargeBcell2010,
title = {Diffuse Large {{B-cell}} Lymphomas with {{CDKN2A}} Deletion Have a Distinct Gene Expression Signature and a Poor Prognosis under {{R-CHOP}} Treatment: A {{GELA}} Study},
shorttitle = {Diffuse Large {{B-cell}} Lymphomas with {{CDKN2A}} Deletion Have a Distinct Gene Expression Signature and a Poor Prognosis under {{R-CHOP}} Treatment},
author = {Jardin, Fabrice and Jais, Jean-Philippe and Molina, Thierry-Jo and Parmentier, Françoise and Picquenot, Jean-Michel and Ruminy, Philippe and Tilly, Hervé and Bastard, Christian and Salles, Gilles-André and Feugier, Pierre and Thieblemont, Catherine and Gisselbrecht, Christian and family=Reynies, given=Aurelien, prefix=de, useprefix=true and Coiffier, Bertrand and Haioun, Corinne and Leroy, Karen},
date = {2010-08-19},
journaltitle = {Blood},
shortjournal = {Blood},
volume = {116},
number = {7},
eprint = {20435884},
eprinttype = {pmid},
pages = {1092--1104},
issn = {1528-0020},
doi = {10.1182/blood-2009-10-247122},
abstract = {Genomic alterations play a crucial role in the development and progression of diffuse large B-cell lymphomas (DLBCLs). We determined gene copy number alterations (GCNAs) of TP53, CDKN2A, CDKN1B, BCL2, MYC, REL, and RB1 with a single polymerase chain reaction (PCR) assay (quantitative multiplex PCR of short fragments [QMPSF]) in a cohort of 114 patients with DLBCL to assess their prognostic value and relationship with the gene expression profile. Losses of TP53 and CDKN2A, observed in 8\% and 35\% of patients, respectively, were significantly associated with a shorter survival after rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) treatment, independently of the International Prognostic Index and of the cell of origin. Analysis of the 9p21 genomic region indicated that transcripts encoding p14ARF and p16INK4A were both disrupted in most patients with CDKN2A deletion. These patients predominantly had an activated B-cell profile and showed a specific gene expression signature, characterized by dysregulation of the RB/E2F pathway, activation of cellular metabolism, and decreased immune and inflammatory responses. These features may constitute the molecular basis sustaining the unfavorable outcome and chemoresistance of this DLBCL subgroup. Detection of TP53 and CDKN2A loss by QMPSF is a powerful tool that could be used for patient stratification in future clinical trials.},
langid = {english},
keywords = {Adult,Aged,Aged 80 and over,Antibodies Monoclonal,Antibodies Monoclonal Murine-Derived,Antineoplastic Combined Chemotherapy Protocols,Cyclin-Dependent Kinase Inhibitor p16,Cyclophosphamide,Doxorubicin,Female,Gene Expression Profiling,Humans,Lymphoma Large B-Cell Diffuse,Male,Middle Aged,Prednisone,Prognosis,Proto-Oncogene Proteins c-bcl-2,Proto-Oncogene Proteins c-myc,Proto-Oncogene Proteins c-rel,Retinoblastoma Protein,Rituximab,Sequence Deletion,Tumor Suppressor Protein p53,Vincristine,Young Adult}
}
@article{guoMutationBTG2Gene2022b,
title = {The {{Mutation}} of {{BTG2 Gene Predicts}} a {{Poor Outcome}} in {{Primary Testicular Diffuse Large B-Cell Lymphoma}}},
author = {Guo, Dan and Hong, Lemin and Ji, Hao and Jiang, Yuwen and Lu, Ling and Wang, Xinfeng and Huang, Hongming},
date = {2022},
journaltitle = {Journal of Inflammation Research},
shortjournal = {J Inflamm Res},
volume = {15},
eprint = {35300216},
eprinttype = {pmid},
pages = {1757--1769},
issn = {1178-7031},
doi = {10.2147/JIR.S341355},
abstract = {INTRODUCTION: Primary testicular diffuse large B-cell lymphoma (PT-DLBCL) is a rare and aggressive form of mature B-cell lymphoma commonly found in elder males, but its genetic features are poorly understood. In this study, we had performed target-sequencing of 360 lymphoma-related genes on 76 PT-DLBCL patients with a median age of 65 (33-89). Our data provide a comprehensive understanding of the landscape of mutations in a small subset of PT-DLBCL. METHODS: A total of 76 PT-DLBCL patients were sequenced, and their clinical data and follow-up data were collected. The relationship between mutated genes, clinical data and prognosis and survival of PT-DLBCL patients was retrospectively analyzed by statistical software. RESULTS: We observed a median of 15 protein-altering variants per patient in our data and was identified recurrent oncogenic mutations of 360 lymphoma-related genes involved in PT-DLBCL, including PIM1 (74\%), MYD88 (50\%), KMT2D (38\%), KMT2C (34\%), BTG2 (34\%), TBL1XR1 (34\%) and ETV6 (24\%). Compared with classic DLBCL, PT-DLBCL showed an increased mutation frequency of PIM1, MYD88, BTG2, while NOTCH1 appeared exclusive mutated with PIM1, MSH3 and ETV6. Cox risk model regression analysis showed that age ≥60 years, IPI 3-5 points, BTG2 gene mutation and extranodal organ invasion suggested poor prognosis. Finally, we constructed an OS predict model of PT-DLBCL patients using above factors with a high accuracy. CONCLUSION: In conclusion, our results revealed genomic characterization of PT-DLBCL, and the mutation of BTG2 was an independent factor predicting a poor prognosis.},
langid = {english},
pmcid = {PMC8923029},
keywords = {BTG2,genetic mutation,primary testicular diffuse large B-cell lymphoma,prognosis,survival}
}
@article{bonatoNFKBIEMutationsAre2024,
title = {{{NFKBIE}} Mutations Are Selected by the Tumor Microenvironment and Contribute to Immune Escape in Chronic Lymphocytic Leukemia},
author = {Bonato, Alice and Chakraborty, Supriya and Bomben, Riccardo and Canarutto, Giulia and Felician, Giulia and Martines, Claudio and Zucchetto, Antonella and Pozzo, Federico and Vujovikj, Marija and Polesel, Jerry and Chiarenza, Annalisa and Del Principe, Maria Ilaria and Del Poeta, Giovanni and D'Arena, Giovanni and Marasca, Roberto and Tafuri, Agostino and Laurenti, Luca and Piazza, Silvano and Dimovski, Aleksandar J. and Gattei, Valter and Efremov, Dimitar G.},
date = {2024-07},
journaltitle = {Leukemia},
shortjournal = {Leukemia},
volume = {38},
number = {7},
eprint = {38486128},
eprinttype = {pmid},
pages = {1511--1521},
issn = {1476-5551},
doi = {10.1038/s41375-024-02224-8},
abstract = {Loss-of-function mutations in NFKBIE, which encodes for the NF-κB inhibitor IκBε, are frequent in chronic lymphocytic leukemia (CLL) and certain other B-cell malignancies and have been associated with accelerated disease progression and inferior responses to chemotherapy. Using in vitro and in vivo murine models and primary patient samples, we now show that NFKBIE-mutated CLL cells are selected by microenvironmental signals that activate the NF-κB pathway and induce alterations within the tumor microenvironment that can allow for immune escape, including expansion of CD8+ T-cells with an exhausted phenotype and increased PD-L1 expression on the malignant B-cells. Consistent with the latter observations, we find increased expression of exhaustion markers on T-cells from patients with NFKBIE-mutated CLL. In addition, we show that NFKBIE-mutated murine CLL cells display selective resistance to ibrutinib and report inferior outcomes to ibrutinib treatment in NFKBIE-mutated CLL patients. These findings suggest that NFKBIE mutations can contribute to CLL progression through multiple mechanisms, including a bidirectional crosstalk with the microenvironment and reduced sensitivity to BTK inhibitor treatment.},
langid = {english},
pmcid = {PMC11216988},
keywords = {Adenine,Animals,CD8-Positive T-Lymphocytes,Humans,Leukemia Lymphocytic Chronic B-Cell,Mice,Mutation,NF-kappa B,Piperidines,Pyrazoles,Pyrimidines,Tumor Escape,Tumor Microenvironment}
}
@article{fanComprehensiveCharacterizationDriver2020,
title = {Comprehensive Characterization of Driver Genes in Diffuse Large {{B}} Cell Lymphoma},
author = {Fan, Zheng and Pei, Renzhi and Sha, Keya and Chen, Lieguang and Wang, Tiantian and Lu, Ying},
date = {2020-07},
journaltitle = {Oncology Letters},
shortjournal = {Oncol Lett},
volume = {20},
number = {1},
eprint = {32565964},
eprinttype = {pmid},
pages = {382--390},
issn = {1792-1074},
doi = {10.3892/ol.2020.11552},
abstract = {Diffuse large B cell lymphoma (DLBCL) is the most common hematological malignancy and is one of the most frequent non-Hodgkin lymphomas. Large-scale genomic studies have defined genetic drivers of DLBCL and their association with functional and clinical outcomes. However, the lymphomagenesis of DLBCL is yet to be fully understood. In the present study, four computational tools OncodriveFM, OncodriveCLUST, integrated Cancer Genome Score and Driver Genes and Pathways were used to detect driver genes and driver pathways involved in DLBCL. The aforementioned tools were also used to perform an integrative investigation of driver genes, including co-expression network, protein-protein interaction, copy number variation and survival analyses. The present study identified 208 driver genes and 31 driver pathways in DLBCL. IGLL5, MLL2, BTG2, B2M, PIM1, CARD11 were the top five frequently mutated genes in DLBCL. NOTCH3, LAMC1, COL4A1, PDGFRB and KDR were the 5 hub genes in the blue module that were associated with patient age. TP53, MYC, EGFR, PTEN, IL6, STAT3, MAPK8, TNF and CDH1 were at the core of the protein-protein interaction network. PRDM1, CDKN2A, CDKN2B, TNFAIP3, RSPO3 were the top five frequently deleted driver genes in DLBCL, while ACTB, BTG2, PLET1, CARD11, DIXDC1 were the top five frequently amplified driver genes in DLBCL. High EIF3B, MLH1, PPP1CA and RECQL4 expression was associated with decreased overall survival rate of patients with DLBCL. High XPO1 and LYN expression were associated with increased overall survival rate of patients with DLBCL. The present study improves the understanding of the biological processes and pathways involved in lymphomagenesis. The driver genes, EIF3B, MLH1, PPP1CA, RECQL4, XPO1 and LYN, pave the way for developing prognostic biomarkers and new therapeutic strategies for DLBCL.},
langid = {english},
pmcid = {PMC7285964},
keywords = {CNV,diffuse large B cell lymphoma,driver gene,driver pathway,overall survival rate,PPI network,WGCNA}
}
@article{lunningMutationChromatinModifiers2015,
title = {Mutation of Chromatin Modifiers; an Emerging Hallmark of Germinal Center {{B-cell}} Lymphomas},
author = {Lunning, M. A. and Green, M. R.},
date = {2015-10-16},
journaltitle = {Blood Cancer Journal},
shortjournal = {Blood Cancer J},
volume = {5},
number = {10},
eprint = {26473533},
eprinttype = {pmid},
pages = {e361},
issn = {2044-5385},
doi = {10.1038/bcj.2015.89},
abstract = {Subtypes of non-Hodgkin's lymphomas align with different stages of B-cell development. Germinal center B-cell (GCB)-like diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and Burkitt's lymphoma (BL) each share molecular similarities with normal GCB cells. Recent next-generation sequencing studies have gained insight into the genetic etiology of these malignancies and revealed a high frequency of mutations within genes encoding proteins that modifying chromatin. These include activating and inactivating mutations of genes that perform post-translational modification of histones and organize chromatin structure. Here, we discuss the function of histone acetyltransferases (CREBBP, EP300), histone methyltransferases (KDM2C/D, EZH2) and regulators of higher order chromatin structure (HIST1H1C/D/E, ARID1A and SMARCA4) that have been reported to be mutated in ⩾5\% of DLBCL, FL or BL. Mutations of these genes are an emerging hallmark of lymphomas with GCB-cell origins, and likely represent the next generation of therapeutic targets for these malignancies.},
langid = {english},
pmcid = {PMC4635197},
keywords = {Animals,Chromatin,Germinal Center,Histone Acetyltransferases,Histone Methyltransferases,Histone-Lysine N-Methyltransferase,Humans,Lymphoma Large B-Cell Diffuse,Mutation,Nuclear Proteins}
}
@article{witjesPrevalenceCytoplasmicActin2020,
title = {Prevalence of {{Cytoplasmic Actin Mutations}} in {{Diffuse Large B-Cell Lymphoma}} and {{Multiple Myeloma}}: {{A Functional Assessment Based}} on {{Actin Three-Dimensional Structures}}},
shorttitle = {Prevalence of {{Cytoplasmic Actin Mutations}} in {{Diffuse Large B-Cell Lymphoma}} and {{Multiple Myeloma}}},
author = {Witjes, Laura and Van Troys, Marleen and Verhasselt, Bruno and Ampe, Christophe},
date = {2020-04-27},
journaltitle = {International Journal of Molecular Sciences},
shortjournal = {Int J Mol Sci},
volume = {21},
number = {9},
eprint = {32349449},
eprinttype = {pmid},
pages = {3093},
issn = {1422-0067},
doi = {10.3390/ijms21093093},
abstract = {Mutations in actins have been linked to several developmental diseases. Their occurrence across different cancers has, however, not been investigated. Using the cBioPortal database we show that human actins are infrequently mutated in patient samples of various cancers types. Nevertheless, ranking these studies by mutational frequency suggest that some have a higher percentage of patients with ACTB and ACTG1 mutations. Within studies on hematological cancers, mutations in ACTB and ACTG1 are associated with lymphoid cancers since none have currently been reported in myeloid cancers. Within the different types of lymphoid cancers ACTB mutations are most frequent in diffuse large B-cell lymphoma (DLBCL) and ACTG1 mutations in multiple myeloma. We mapped the ACTB and ACTG1 mutations found in these two cancer types on the 3D-structure of actin showing they are in regions important for actin polymer formation or binding to myosin. The potential effects of the mutations on actin properties imply that mutations in cytoplasmic actins deserve dedicated research in DLBCL and multiple myeloma.},
langid = {english},
pmcid = {PMC7247664},
keywords = {ACTB,ACTG1,actin mutations,Actins,Alleles,Biomarkers Tumor,cBioPortal,Cytoplasm,Databases Genetic,F-actin,Gene Amplification,Gene Deletion,Genetic Association Studies,Genetic Predisposition to Disease,Humans,lymphoid cancer,Lymphoma Large B-Cell Diffuse,meta-analysis of patient data,Models Molecular,Multiple Myeloma,Mutation,Mutation Rate,myosin,Organ Specificity,patient cancer data,plasma cell myeloma,Protein Conformation,Software,Structure-Activity Relationship}
}
@article{delageBTG1InactivationDrives2023,
title = {{{BTG1}} Inactivation Drives Lymphomagenesis and Promotes Lymphoma Dissemination through Activation of {{BCAR1}}},
author = {Delage, Lorric and Lambert, Mireille and Bardel, Émilie and Kundlacz, Cindy and Chartoire, Dimitri and Conchon, Axel and Peugnet, Anne-Laure and Gorka, Lucas and Auberger, Patrick and Jacquel, Arnaud and Soussain, Carole and Destaing, Olivier and Delecluse, Henri-Jacques and Delecluse, Susanne and Merabet, Samir and Traverse-Glehen, Alexandra and Salles, Gilles and Bachy, Emmanuel and Billaud, Marc and Ghesquières, Hervé and Genestier, Laurent and Rouault, Jean-Pierre and Sujobert, Pierre},
date = {2023-03-09},
journaltitle = {Blood},
shortjournal = {Blood},
volume = {141},
number = {10},
eprint = {36375119},
eprinttype = {pmid},
pages = {1209--1220},
issn = {1528-0020},
doi = {10.1182/blood.2022016943},
abstract = {Understanding the functional role of mutated genes in cancer is required to translate the findings of cancer genomics into therapeutic improvement. BTG1 is recurrently mutated in the MCD/C5 subtype of diffuse large B-cell lymphoma (DLBCL), which is associated with extranodal dissemination. Here, we provide evidence that Btg1 knock out accelerates the development of a lethal lymphoproliferative disease driven by Bcl2 overexpression. Furthermore, we show that the scaffolding protein BCAR1 is a BTG1 partner. Moreover, after BTG1 deletion or expression of BTG1 mutations observed in patients with DLBCL, the overactivation of the BCAR1-RAC1 pathway confers increased migration ability in~vitro and in~vivo. These modifications are targetable with the SRC inhibitor dasatinib, which opens novel therapeutic opportunities in BTG1 mutated DLBCL.},
langid = {english},
keywords = {Crk-Associated Substrate Protein,Genes cdc,Humans,Lymphoma Large B-Cell Diffuse,Mutation,Neoplasm Proteins}
}
@article{mlynarczykBTG1MutationYields2023,
title = {{{BTG1}} Mutation Yields Supercompetitive {{B}} Cells Primed for Malignant Transformation},
author = {Mlynarczyk, Coraline and Teater, Matt and Pae, Juhee and Chin, Christopher R. and Wang, Ling and Arulraj, Theinmozhi and Barisic, D. and Papin, A. and Hoehn, Kenneth B. and Kots, E. and Ersching, Jonatan and Bandyopadhyay, A. and Barin, Ersilia and Poh, Hui Xian and Evans, Chiara M. and Chadburn, A. and Chen, Zhengming and Shen, Hao and Isles, H. and Pelzer, Benedikt W. and Tsialta, Ioanna and Doane, A. and Geng, H. and Rehman, Muhammad Hassan and Melnick, Jonah and Morgan, Wyatt and Nguyen, D. and Elemento, O. and Kharas, Michael G. and Jaffrey, S. and Scott, D. and Khelashvili, G. and Meyer-Hermann, M. and Victora, G. and Melnick, A.},
date = {2023},
journaltitle = {Science},
shortjournal = {Science},
volume = {379},
doi = {10.1126/science.abj7412}
}
@article{balinas-gaviraFrequentMutationsAminoterminal2020,
title = {Frequent Mutations in the Amino-Terminal Domain of {{BCL7A}} Impair Its Tumor Suppressor Role in {{DLBCL}}},
author = {Baliñas-Gavira, Carlos and Rodríguez, M. I. and Andrades, Á and Cuadros, M. and Álvarez-Pérez, J. and Álvarez-Prado, Ángel F. and family=Yébenes, given=V. G., prefix=de, useprefix=false and Sanchez-Hernandez, S. and Fernández-Vigo, Elvira and Muñoz, Javier and Martín, F. and Ramiro, A. and Martinez-Climent, J. and Medina, P.},
date = {2020},
journaltitle = {Leukemia},
shortjournal = {Leukemia},
pages = {1--14},
doi = {10.1038/s41375-020-0919-5}
}
@article{phelanBCL10MutantsArchitects2022,
title = {{{BCL10 Mutants}}: {{Architects}} of {{Oncogenic Signaling Provide}} a {{Blueprint}} for {{Precision Medicine}}},
shorttitle = {{{BCL10 Mutants}}},
author = {Phelan, James D. and Oellerich, Thomas},
date = {2022-08-05},
journaltitle = {Cancer Discovery},
shortjournal = {Cancer Discov},
volume = {12},
number = {8},
eprint = {35929131},
eprinttype = {pmid},
pages = {1844--1846},
issn = {2159-8290},
doi = {10.1158/2159-8290.CD-22-0614},
abstract = {BCL10, a key activator of NF-κB downstream of oncogenic B-cell receptor signaling, is mutated in nearly 40\% of the BN2/C1 genetic subtype of diffuse large B-cell lymphoma, but how these mutations function to augment signaling and their relevance to targeted precision medicine agents remains unclear. In this issue of Cancer Discovery, Xia and colleagues demonstrate distinct mechanisms of oncogenic signaling regulation and therapeutic vulnerabilities among different recurrent BCL10 mutations. See related article by Xia et al., p. 1922 (1).},
langid = {english},
keywords = {B-Cell CLL-Lymphoma 10 Protein,Carcinogenesis,CARD Signaling Adaptor Proteins,Humans,Mutation,NF-kappa B,Precision Medicine,Signal Transduction}
}
@article{xiaBCL10MutationsDefine2022,
title = {{{BCL10 Mutations Define Distinct Dependencies Guiding Precision Therapy}} for {{DLBCL}}},
author = {Xia, Min and David, Liron and Teater, Matt and Gutierrez, Johana and Wang, Xiang and Meydan, Cem and Lytle, Andrew and Slack, Graham W. and Scott, David W. and Morin, Ryan D. and Onder, Ozlem and Elenitoba-Johnson, Kojo S. J. and Zamponi, Nahuel and Cerchietti, Leandro and Lu, Tianbao and Philippar, Ulrike and Fontan, Lorena and Wu, Hao and Melnick, Ari M.},
date = {2022-08-05},
journaltitle = {Cancer Discovery},
shortjournal = {Cancer Discov},
volume = {12},
number = {8},
eprint = {35658124},
eprinttype = {pmid},
pages = {1922--1941},
issn = {2159-8290},
doi = {10.1158/2159-8290.CD-21-1566},
abstract = {Activated B cell-like diffuse large B-cell lymphomas (ABC-DLBCL) have unfavorable outcomes and chronic activation of CARD11-BCL10-MALT1 (CBM) signal amplification complexes that form due to polymerization of BCL10 subunits, which is affected by recurrent somatic mutations in ABC-DLBCLs. Herein, we show that BCL10 mutants fall into at least two functionally distinct classes: missense mutations of the BCL10 CARD domain and truncation of its C-terminal tail. Truncating mutations abrogated a motif through which MALT1 inhibits BCL10 polymerization, trapping MALT1 in its activated filament-bound state. CARD missense mutations enhanced BCL10 filament formation, forming glutamine network structures that stabilize BCL10 filaments. Mutant forms of BCL10 were less dependent on upstream CARD11 activation and thus manifested resistance to BTK inhibitors, whereas BCL10 truncating but not CARD mutants were hypersensitive to MALT1 inhibitors. Therefore, BCL10 mutations are potential biomarkers for BTK inhibitor resistance in ABC-DLBCL, and further precision can be achieved by selecting therapy based on specific biochemical effects of distinct mutation classes. SIGNIFICANCE: ABC-DLBCLs feature frequent mutations of signaling mediators that converge on the CBM complex. We use structure-function approaches to reveal that BCL10 mutations fall into two distinct biochemical classes. Both classes confer resistance to BTK inhibitors, whereas BCL10 truncations confer hyperresponsiveness to MALT1 inhibitors, providing a road map for precision therapies in ABC-DLBCLs. See related commentary by Phelan and Oellerich, p. 1844. This article is highlighted in the In This Issue feature, p. 1825.},
langid = {english},
pmcid = {PMC9357155},
keywords = {B-Cell CLL-Lymphoma 10 Protein,CARD Signaling Adaptor Proteins,Guanylate Cyclase,Humans,Lymphoma Large B-Cell Diffuse,Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein,Mutation,Signal Transduction}
}
@article{dengSMARCA4HaploinsufficientCell2024,
title = {{{SMARCA4}} Is a Haploinsufficient {{B}} Cell Lymphoma Tumor Suppressor That Fine-Tunes Centrocyte Cell Fate Decisions},
author = {Deng, Qing and Lakra, Priya and Gou, Panhong and Yang, Haopeng and Meydan, Cem and Teater, Matthew and Chin, Christopher and Zhang, Wenchao and Dinh, Tommy and Hussein, Usama and Li, Xubin and Rojas, Estela and Liu, Weiguang and Reville, Patrick K. and Kizhakeyil, Atish and Barisic, Darko and Parsons, Sydney and Wilson, Ashley and Henderson, Jared and Scull, Brooks and Gurumurthy, Channabasavaiah and Vega, Francisco and Chadburn, Amy and Cuglievan, Branko and El-Mallawany, Nader Kim and Allen, Carl and Mason, Christopher and Melnick, Ari and Green, Michael R.},
date = {2024-04-08},
journaltitle = {Cancer Cell},
shortjournal = {Cancer Cell},
volume = {42},
number = {4},
eprint = {38458188},
eprinttype = {pmid},
pages = {605-622.e11},
issn = {1878-3686},
doi = {10.1016/j.ccell.2024.02.011},
abstract = {SMARCA4 encodes one of two mutually exclusive ATPase subunits in the BRG/BRM associated factor (BAF) complex that is recruited by transcription factors (TFs) to drive chromatin accessibility and transcriptional activation. SMARCA4 is among the most recurrently mutated genes in human cancer, including ∼30\% of germinal center (GC)-derived Burkitt lymphomas. In mice, GC-specific Smarca4 haploinsufficiency cooperated with MYC over-expression to drive lymphomagenesis. Furthermore, monoallelic Smarca4 deletion drove GC hyperplasia with centroblast polarization via significantly increased rates of centrocyte recycling to the dark zone. Mechanistically, Smarca4 loss reduced the activity of TFs that are activated in centrocytes to drive GC-exit, including SPI1 (PU.1), IRF family, and NF-κB. Loss of activity for these factors phenocopied aberrant BCL6 activity within murine centrocytes and human Burkitt lymphoma cells. SMARCA4 therefore facilitates chromatin accessibility for TFs that shape centrocyte trajectories, and loss of fine-control of these programs biases toward centroblast cell-fate, GC hyperplasia and lymphoma.},
langid = {english},
pmcid = {PMC11003852},
keywords = {Animals,B-cell,BAF,Chromatin,DNA Helicases,epigenetics,germinal center,Haploinsufficiency,Humans,Hyperplasia,immunology,lymphoma,Lymphoma B-Cell,Mice,Nuclear Proteins,SMARCA4,SWI/SNF,transcription,Transcription Factors}
}
@article{challa-malladiCombinedGeneticInactivation2011,
title = {Combined Genetic Inactivation of Β2-{{Microglobulin}} and {{CD58}} Reveals Frequent Escape from Immune Recognition in Diffuse Large {{B}} Cell Lymphoma},
author = {Challa-Malladi, Madhavi and Lieu, Yen K. and Califano, Olivia and Holmes, Antony B. and Bhagat, Govind and Murty, Vundavalli V. and Dominguez-Sola, David and Pasqualucci, Laura and Dalla-Favera, Riccardo},
date = {2011-12-13},
journaltitle = {Cancer Cell},
shortjournal = {Cancer Cell},
volume = {20},
number = {6},
eprint = {22137796},
eprinttype = {pmid},
pages = {728--740},
issn = {1878-3686},
doi = {10.1016/j.ccr.2011.11.006},
abstract = {We report that diffuse large B cell lymphoma (DLBCL) commonly fails to express cell-surface molecules necessary for the recognition of tumor cells by immune-effector cells. In 29\% of cases, mutations and deletions inactivate the β2-Microglobulin gene, thus preventing the cell-surface expression of the HLA class-I (HLA-I) complex that is necessary for recognition by CD8(+) cytotoxic T~cells. In 21\% of cases, analogous lesions~involve the CD58 gene, which encodes a molecule involved in T and natural killer cell-mediated responses. In addition to gene inactivation, alternative mechanisms lead to aberrant expression of HLA-I and CD58 in {$>$}60\% of DLBCL. These two events are significantly associated in this disease, suggesting that they are coselected during lymphomagenesis for their combined role in escape from immune-surveillance.},
langid = {english},
pmcid = {PMC3660995},
keywords = {beta 2-Microglobulin,CD58 Antigens,Cell Line Tumor,Coculture Techniques,Cytotoxicity Immunologic,DNA Copy Number Variations,DNA Mutational Analysis,Genetic Association Studies,Genotype,Histocompatibility Antigens Class I,Humans,Killer Cells Natural,Lymphoma Large B-Cell Diffuse,Mutation,Polymorphism Single Nucleotide,Protein Stability,Transcription Genetic},
}
@article{nieGenomewideCRISPRScreens2021,
title = {Genome-Wide {{CRISPR}} Screens Reveal Synthetic Lethal Interaction between {{CREBBP}} and {{EP300}} in Diffuse Large {{B-cell}} Lymphoma},
author = {Nie, Man and Du, Likun and Ren, Weicheng and Joung, Julia and Ye, Xiaofei and Shi, Xi and Ciftci, Sibel and Liu, Dongbing and Wu, Kui and Zhang, Feng and Pan-Hammarström, Qiang},
date = {2021-04-28},
journaltitle = {Cell Death \& Disease},
shortjournal = {Cell Death Dis},
volume = {12},
number = {5},
eprint = {33911074},
eprinttype = {pmid},
pages = {419},
issn = {2041-4889},
doi = {10.1038/s41419-021-03695-8},
abstract = {Diffuse large B-cell lymphoma (DLBCL) is the most common type of aggressive lymphoid malignancy and a highly heterogeneous disease. In this study, we performed whole-genome and transcriptome sequencing, and a genome-wide CRISPR-Cas9-knockout screen to study an activated B-cell-like DLBCL cell line (RC-K8). We identified a distinct pattern of genetic essentialities in RC-K8, including a dependency on CREBBP and MDM2. The dependency on CREBBP is associated with a balanced translocation involving EP300, which results in a truncated form of the protein that lacks the critical histone acetyltransferase (HAT) domain. The synthetic lethal interaction between CREBBP and EP300 genes, two frequently mutated epigenetic modulators in B-cell lymphoma, was further validated in the previously published CRISPR-Cas9 screens and inhibitor assays. Our study suggests that integration of the unbiased functional screen results with genomic and transcriptomic data can identify both common and unique druggable vulnerabilities in DLBCL and histone acetyltransferases inhibition could be a therapeutic option for CREBBP or EP300 mutated cases.},
langid = {english},
pmcid = {PMC8080727},
keywords = {Cell Line Tumor,Clustered Regularly Interspaced Short Palindromic Repeats,CREB-Binding Protein,E1A-Associated p300 Protein,Gene Knockdown Techniques,Humans,Lymphoma Large B-Cell Diffuse}
}
@article{veazeyCARM1InhibitionReduces2020,
title = {{{CARM1}} Inhibition Reduces Histone Acetyltransferase Activity Causing Synthetic Lethality in {{CREBBP}}/{{EP300-mutated}} Lymphomas},
author = {Veazey, Kylee J. and Cheng, Donghang and Lin, Kevin and Villarreal, Oscar D. and Gao, Guozhen and Perez-Oquendo, Mabel and Van, Hieu T. and Stratton, Sabrina A. and Green, Michael and Xu, Han and Lu, Yue and Bedford, Mark T. and Santos, Margarida Almeida},
date = {2020-12},
journaltitle = {Leukemia},
shortjournal = {Leukemia},
volume = {34},
number = {12},
eprint = {32576962},
eprinttype = {pmid},
pages = {3269--3285},
issn = {1476-5551},
doi = {10.1038/s41375-020-0908-8},
abstract = {Somatic mutations affecting CREBBP and EP300 are a hallmark of diffuse large B-cell lymphoma (DLBCL). These mutations are frequently monoallelic, within the histone acetyltransferase (HAT) domain and usually mutually exclusive, suggesting that they might affect a common pathway, and their residual WT expression is required for cell survival. Using in vitro and in vivo models, we found that inhibition of CARM1 activity (CARM1i) slows DLBCL growth, and that the levels of sensitivity are positively correlated with the CREBBP/EP300 mutation load. Conversely, treatment of DLBCLs that do not have CREBBP/EP300 mutations with CARM1i and a CBP/p300 inhibitor revealed a strong synergistic effect. Our mechanistic data show that CARM1i further reduces the HAT activity of CBP genome wide and downregulates CBP-target genes in DLBCL cells, resulting in a synthetic lethality that leverages the mutational status of CREBBP/EP300 as a biomarker for the use of small-molecule inhibitors of CARM1 in DLBCL and other cancers.},
langid = {english},
pmcid = {PMC7688486},
keywords = {Acetylation,Animals,Cell Line,CREB-Binding Protein,Down-Regulation,E1A-Associated p300 Protein,Histone Acetyltransferases,Lymphoma Large B-Cell Diffuse,Mice,Mice Inbred NOD,Mice SCID,Protein-Arginine N-Methyltransferases,Synthetic Lethal Mutations}
}
@article{scholzeCombinedEZH2Bcl22020,
title = {Combined {{EZH2}} and {{Bcl-2}} Inhibitors as Precision Therapy for Genetically Defined {{DLBCL}} Subtypes.},
author = {Scholze, Hanna and Stephenson, Regan E. and Reynolds, Raymond and Shah, Shivem B. and Puri, R. and Butler, Scott D. and Trujillo-Alonso, Vicenta and Teater, Matt and family=Besien, given=Herman, prefix=van, useprefix=false and Gibbs-Curtis, Destini and Ueno, H. and Parvin, S. and Letai, A. and Mathew, S. and Singh, Ankur and Cesarman, E. and Melnick, A. and Giulino‐Roth, L.},
date = {2020},
journaltitle = {Blood Advances},
shortjournal = {Blood advances},
volume = {4 20},
pages = {5226--5231},
doi = {10.1182/bloodadvances.2020002580}
}
@article{yapSomaticMutationsEZH22011,
title = {Somatic Mutations at {{EZH2 Y641}} Act Dominantly through a Mechanism of Selectively Altered {{PRC2}} Catalytic Activity, to Increase {{H3K27}} Trimethylation},
author = {Yap, Damian B. and Chu, Justin and Berg, Tobias and Schapira, Matthieu and Cheng, S.-W. Grace and Moradian, Annie and Morin, Ryan D. and Mungall, Andrew J. and Meissner, Barbara and Boyle, Merrill and Marquez, Victor E. and Marra, Marco A. and Gascoyne, Randy D. and Humphries, R. Keith and Arrowsmith, Cheryl H. and Morin, Gregg B. and Aparicio, Samuel A. J. R.},
date = {2011-02-24},
journaltitle = {Blood},
shortjournal = {Blood},
volume = {117},
number = {8},
eprint = {21190999},
eprinttype = {pmid},
pages = {2451--2459},
issn = {1528-0020},
doi = {10.1182/blood-2010-11-321208},
abstract = {Next-generation sequencing of follicular lymphoma and diffuse-large B-cell lymphoma has revealed frequent somatic, heterozygous Y641 mutations in the histone methyltransferase EZH2. Heterozygosity and the presence of equal quantities of both mutant and wild-type mRNA and expressed protein suggest a dominant mode of action. Surprisingly, B-cell lymphoma cell lines and lymphoma samples harboring heterozygous EZH2(Y641) mutations have increased levels of histone H3 Lys-27-specific trimethylation (H3K27me3). Expression of EZH2(Y641F/N) mutants in cells with EZH2(WT) resulted in an increase of H3K27me3 levels in vivo. Structural modeling of EZH2(Y641) mutants suggests a "Tyr/Phe switch" model whereby structurally neutral, nontyrosine residues at position 641 would decrease affinity for unmethylated and monomethylated H3K27 substrates and potentially favor trimethylation. We demonstrate, using in vitro enzyme assays of reconstituted PRC2 complexes, that Y641 mutations result in a decrease in monomethylation and an increase in trimethylation activity of the enzyme relative to the wild-type enzyme. This represents the first example of a disease-associated gain-of-function mutation in a histone methyltransferase, whereby somatic EZH2 Y641 mutations in lymphoma act dominantly to increase, rather than decrease, histone methylation. The dominant mode of action suggests that allele-specific EZH2 inhibitors should be a future therapeutic strategy for this disease.},
langid = {english},
pmcid = {PMC3062411},
keywords = {Biopsy,Catalysis,Cell Line Tumor,DNA-Binding Proteins,Enhancer of Zeste Homolog 2 Protein,Histone-Lysine N-Methyltransferase,Histones,Humans,Lymphoma,Lymphoma Large B-Cell Diffuse,Methylation,Models Molecular,Mutation Missense,Polycomb Repressive Complex 2,Substrate Specificity,Transcription Factors}
}
@article{hartmannHighlyRecurrentMutations2016,
title = {Highly Recurrent Mutations of {{SGK1}}, {{DUSP2}} and {{JUNB}} in Nodular Lymphocyte Predominant {{Hodgkin}} Lymphoma},
author = {Hartmann, S. and Schuhmacher, B. and Rausch, T. and Fuller, L. and Döring, C. and Weniger, M. and Lollies, A. and Weiser, C. and Thurner, L. and Rengstl, B. and Brunnberg, U. and Vornanen, M. and Pfreundschuh, M. and Benes, V. and Küppers, R. and Newrzela, S. and Hansmann, M.-L.},
date = {2016-04},
journaltitle = {Leukemia},
shortjournal = {Leukemia},
volume = {30},
number = {4},
eprint = {26658840},
eprinttype = {pmid},
pages = {844--853},
issn = {1476-5551},
doi = {10.1038/leu.2015.328},
abstract = {Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL)-a subtype of Hodgkin lymphoma (HL)-is characterized by a low content of tumor cells, the lymphocyte predominant (LP) cells. Transformation into diffuse large B-cell lymphoma (DLBCL) occurs in about 10\% of patients. We performed whole-genome mutation analysis of the DLBCL components from two composite lymphomas consisting of clonally related NLPHL and DLBCL as a means to identify candidate tumor suppressor genes and oncogenes in NLPHL. The analysis of LP cells for selected mutations of the DLBCL revealed that most mutations are also present in the LP cells, indicating a close relationship between the two components. The analysis of 62 selected genes in NLPHL by targeted ultra-deep sequencing revealed three novel highly recurrently mutated genes (each mutated in \textasciitilde 50\% of cases), that is, DUSP2, SGK1 and JUNB. SGK1 was expressed in the LP cells of primary NLPHL cases and in the NLPHL cell line DEV. Administration of an SGK1 inhibitor induced apoptosis in the NLPHL cell line DEV and the DLBCL cell line Farage, suggesting a pathogenetic role of SGK1 in the LP and DLBCL cells. In summary, the present study identifies SGK1, DUSP2 and JUNB as novel key players in the pathogenesis of NLPHL.},
langid = {english},
keywords = {Adult,DNA Mutational Analysis,Dual Specificity Phosphatase 2,High-Throughput Nucleotide Sequencing,Hodgkin Disease,Humans,Immediate-Early Proteins,Immunophenotyping,Lymph Nodes,Lymphocytes,Lymphoma Follicular,Lymphoma Large B-Cell Diffuse,Male,Middle Aged,Mutation,Neoplasm Staging,Prognosis,Protein Serine-Threonine Kinases,Transcription Factors}
}
@article{schuhmacherJUNBDUSP2SGK12019,
title = {{{JUNB}}, {{DUSP2}}, {{SGK1}}, {{SOCS1}} and {{CREBBP}} Are Frequently Mutated in {{T-cell}}/Histiocyte-Rich Large {{B-cell}} Lymphoma},
author = {Schuhmacher, Bianca and Bein, Julia and Rausch, Tobias and Benes, Vladimir and Tousseyn, Thomas and Vornanen, Martine and Ponzoni, Maurilio and Thurner, Lorenz and Gascoyne, Randy and Steidl, Christian and Küppers, Ralf and Hansmann, Martin-Leo and Hartmann, Sylvia},
date = {2019-02},
journaltitle = {Haematologica},
shortjournal = {Haematologica},
volume = {104},
number = {2},
eprint = {30213827},
eprinttype = {pmid},
pages = {330--337},
issn = {1592-8721},
doi = {10.3324/haematol.2018.203224},
abstract = {T-cell/histiocyte-rich large B-cell lymphoma is a rare aggressive lymphoma showing histopathological overlap with nodular lymphocyte-predominant Hodgkin lymphoma. Despite differences in tumor microenvironment and clinical behavior, the tumor cells of both entities show remarkable similarities, suggesting that both lymphomas might represent a spectrum of the same disease. To address this issue, we investigated whether these entities share mutations. Ultra-deep targeted resequencing of six typical and 11 histopathological variants of nodular lymphocyte-predominant Hodgkin lymphoma, and nine cases of T-cell/histiocyte-rich large B-cell lymphoma revealed that genes recurrently mutated in nodular lymphocyte-predominant Hodgkin lymphoma are affected by mutations at similar frequencies in T-cell/histiocyte-rich large B-cell lymphoma. The most recurrently mutated genes were JUNB, DUSP2, SGK1, SOCS1 and CREBBP, which harbored mutations more frequently in T-cell/histiocyte-rich large B-cell lymphoma and the histopathological variants of nodular lymphocyte-predominant Hodgkin lymphoma than in its typical form. Mutations in JUNB, DUSP2, SGK1 and SOCS1 were highly enriched for somatic hypermutation hotspot sites, suggesting an important role of aberrant somatic hypermutation in the generation of these somatic mutations and thus in the pathogenesis of both lymphoma entities. Mutations in JUNB are generally rarely observed in malignant lymphomas and thus are relatively specific for nodular lymphocyte-predominant Hodgkin lymphoma and T-cell/histiocyte-rich large B-cell lymphoma at such high frequencies (5/17 and 5/9 cases with JUNB mutations, respectively). Taken together, the findings of the present study further support a close relationship between T-cell/histiocyte-rich large B-cell lymphoma and nodular lymphocyte-predominant Hodgkin lymphoma by showing that they share highly recurrent genetic lesions.},
langid = {english},
pmcid = {PMC6355500},
keywords = {Adult,Aged,Aged 80 and over,Biomarkers Tumor,CREB-Binding Protein,Dual Specificity Phosphatase 2,Female,Histiocytes,Humans,Immediate-Early Proteins,Lymphoma Large B-Cell Diffuse,Male,Middle Aged,Mutation,Mutation Rate,Protein Serine-Threonine Kinases,Suppressor of Cytokine Signaling 1 Protein,T-Lymphocytes,Transcription Factors,Young Adult}
}
@article{wilsonEffectIbrutinibRCHOP2021,
title = {Effect of Ibrutinib with {{R-CHOP}} Chemotherapy in Genetic Subtypes of {{DLBCL}}},
author = {Wilson, Wyndham H. and Wright, George W. and Huang, Da Wei and Hodkinson, Brendan and Balasubramanian, Sriram and Fan, Yue and Vermeulen, Jessica and Shreeve, Martin and Staudt, Louis M.},
date = {2021-12-13},
journaltitle = {Cancer Cell},
shortjournal = {Cancer Cell},
volume = {39},
number = {12},
eprint = {34739844},
eprinttype = {pmid},
pages = {1643-1653.e3},
issn = {1878-3686},
doi = {10.1016/j.ccell.2021.10.006},
abstract = {In diffuse large B cell lymphoma (DLBCL), tumors belonging to the ABC but not GCB gene expression subgroup rely upon chronic active B cell receptor signaling for viability, a dependency that is targetable by ibrutinib. A phase III trial ("Phoenix;" ClinicalTrials.gov: NCT01855750) showed a survival benefit of ibrutinib addition to R-CHOP chemotherapy in younger patients with non-GCB DLBCL, but the molecular basis for this benefit was unclear. Analysis of biopsies from Phoenix trial patients revealed three previously characterized genetic subtypes of DLBCL: MCD, BN2, and N1. The 3-year event-free survival of younger patients (age ≤60 years) treated with ibrutinib plus R-CHOP was 100\% in the MCD and N1 subtypes while the survival of patients with these subtypes treated with R-CHOP alone was significantly inferior (42.9\% and 50\%, respectively). This work provides a mechanistic understanding of the benefit of ibrutinib addition to chemotherapy, supporting its use in younger patients with non-GCB DLBCL.},
langid = {english},
pmcid = {PMC8722194},
keywords = {ABC DLBCL,Adenine,Aged,Antineoplastic Combined Chemotherapy Protocols,BTK inhibitor,cancer genomics,CD79B,Cyclophosphamide,Doxorubicin,Female,Humans,Lymphoma Large B-Cell Diffuse,Male,memory B cell,Middle Aged,MYD88,NOTCH1,Piperidines,precision medicine,Prednisone,Rituximab,Vincristine}
}
@article{flumannInducibleCd79bMutation2024,
title = {An Inducible {{Cd79b}} Mutation Confers Ibrutinib Sensitivity in Mouse Models of {{Myd88-driven}} Diffuse Large {{B-cell}} Lymphoma},
author = {Flümann, Ruth and Hansen, Julia and Meinel, Jörn and Pfeiffer, Pauline and Goldfarb Wittkopf, Hannah and Lütz, Anna and Wirtz, Jessica and Möllmann, Michael and Zhou, Tanja and Tabatabai, Areya and Lohmann, Tim and Jauch, Maximilian and Beleggia, Filippo and Pelzer, Benedikt and Ullrich, Fabian and Höfmann, Svenja and Arora, Aastha and Persigehl, Thorsten and Büttner, Reinhard and family=Tresckow, given=Bastian, prefix=von, useprefix=true and Klein, Sebastian and Jachimowicz, Ron D. and Reinhardt, Hans Christian and Knittel, Gero},
date = {2024-03-12},
journaltitle = {Blood Advances},
shortjournal = {Blood Adv},
volume = {8},
number = {5},
eprint = {38060829},
eprinttype = {pmid},
pages = {1063--1074},
issn = {2473-9537},
doi = {10.1182/bloodadvances.2023011213},
abstract = {Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive lymphoma and constitutes a highly heterogenous disease. Recent comprehensive genomic profiling revealed the identity of numerous molecularly defined DLBCL subtypes, including a cluster which is characterized by recurrent aberrations in MYD88, CD79B, and BCL2, as well as various lesions promoting a block in plasma cell differentiation, including PRDM1, TBL1XR1, and SPIB. Here, we generated a series of autochthonous mouse models to mimic this DLBCL cluster and specifically focused on the impact of Cd79b mutations in this setting. We show that canonical Cd79b immunoreceptor tyrosine-based activation motif (ITAM) mutations do not accelerate Myd88- and BCL2-driven lymphomagenesis. Cd79b-mutant murine DLBCL were enriched for IgM surface expression, reminiscent of their human counterparts. Moreover, Cd79b-mutant lymphomas displayed a robust formation of cytoplasmic signaling complexes involving MYD88, CD79B, MALT1, and BTK. These~complexes were disrupted upon pharmacological BTK inhibition. The BTK inhibitor-mediated disruption of these signaling complexes translated into a selective ibrutinib sensitivity of lymphomas harboring combined Cd79b and Myd88 mutations. Altogether, this in-depth cross-species comparison provides a framework for the development of molecularly targeted therapeutic intervention strategies in DLBCL.},
langid = {english},
pmcid = {PMC10907402},
keywords = {Adenine,Animals,Lymphoma Large B-Cell Diffuse,Mice,Mutation,Myeloid Differentiation Factor 88,Piperidines,Proto-Oncogene Proteins c-bcl-2}
}
@article{mandatoAbstractA38Cd702022,
title = {Abstract {{A38}}: {{Cd70}} Genetic Perturbation Limits the Development of an Effective {{CD8}}+ {{T-cell}} Immune Response to {{Bcl6-driven}} Diffuse Large {{B-cell}} Lymphoma},
shorttitle = {Abstract {{A38}}},
author = {Mandato, Elisa and Calabretta, Eleonora and Bai, Gali and Song, Li and Sun, Yanbo and Shanmugam, Vignesh and Paczkowska, Julia and Choi, Il-Kyu and Redd, Robert and Tang, Ming and Lawton, Lee N and Neuberg, Donna and Rodig, Scott and Michor, Franziska and Zhang, Baochun and Shipp, Margaret A},
date = {2022-09-06},
journaltitle = {Blood Cancer Discovery},
shortjournal = {Blood Cancer Discovery},
volume = {3},
pages = {A38},
issn = {2643-3230},
doi = {10.1158/2643-3249.LYMPHOMA22-A38},
abstract = {Multiple immunomodulatory pathways shape the development of anti-tumor immune responses to lymphoid malignancies. We previously defined the recurrent genetic alterations in diffuse large B-cell lymphoma (DLBCL) and identified associated substructure and additional potential genetic bases for immune escape. CD70 was the most commonly perturbed immune response pathway component in our cohort of primary DLBCLs; alterations included inactivating mutations and copy loss. CD70 co-stimulation of CD27+ T cells induces antigen-dependent T-cell expansion and immune surveillance of normal and malignant B cells. Given the frequent co-association of CD70 alterations and BCL6 translocations in our DLBCL patient series, we assessed the consequences of Cd70 deficiency on Bcl6-driven lymphomagenesis in a murine model. We crossed previously generated Cd70−/- and Bcl6tg/+ mice to obtain Cd70−/−; Bcl6tg/+ animals. In our aging cohorts, Cd70−/−; Bcl6tg/+ mice developed significantly increased numbers of histopathologically confirmed DLBCLs at earlier timepoints, compared to Bcl6tg/+ animals. Both the Cd70−/−; Bcl6tg/+ and Bcl6tg/+ mice that were euthanized for symptoms exhibited massive splenomegaly and lymphomatous splenic infiltration. None of the wild-type (WT) and Cd70−/- animals developed lymphoma. To characterize potential differences in anti-tumor responses in Cd70−/−; Bcl6tg/+ versus Bcl6tg/+ mice, we harvested spleens from asymptomatic animals in each cohort at 6, 14 and 18 months (mo). Cd70−/−; Bcl6tg/+ mice exhibited significantly earlier onset splenomegaly than Bcl6tg/+ animals (both in comparison with WT mice). We performed single cell RNA sequencing of splenic cell suspensions from each murine cohort at the above-mentioned predetermined timepoints (6, 14 and 18 mo) and describe genotype-related changes in splenic CD8+ T-cell infiltration in this abstract. Our study revealed an age-related decline in the percentages of naive CD8+ T cells in all genotypes, with more striking and earlier changes in Cd70−/−; Bcl6tg/+ animals. Cd70−/−; Bcl6tg/+ and Bcl6tg/+ mice exhibited a selective and significant expansion of CD8+ cytotoxic T cells (CTLs), which expressed Gzmb and Prf1 and the exhaustion markers, Pdcd1, Lag3, Tigit, Tox and Tim3, and exhibited clonal expansion. At 6 mo, prior to splenic enlargement and the development of symptoms, CD8+ CTLs in Cd70−/−; Bcl6tg/+ animals expressed significantly higher levels of exhaustion markers than those in Bcl6tg/+ mice. Consistent with this finding, there was a more limited expansion and a subsequent contraction of these splenic CD8+ CTLs in Cd70−/−; Bcl6tg/+ mice, in comparison to Bcl6tg/+ animals. Taken together, these findings suggest that initial anti-tumor immune responses are less effective in Cd70−/−; Bcl6tg/+ mice than in Bcl6tg/+ animals and highlight the likely importance of CD70/CD27 co-stimulation in CD8+ T-cell response to Bcl6-driven DLBCL.Citation Format: Elisa Mandato, Eleonora Calabretta, Gali Bai, Li Song, Yanbo Sun, Vignesh Shanmugam, Julia Paczkowska, Il-Kyu Choi, Robert Redd, Ming Tang, Lee N Lawton, Donna Neuberg, Scott Rodig, Franziska Michor, Baochun Zhang, Margaret A Shipp. Cd70 genetic perturbation limits the development of an effective CD8+ T-cell immune response to Bcl6-driven diffuse large B-cell lymphoma [abstract]. In: Proceedings of the Third AACR International Meeting: Advances in Malignant Lymphoma: Maximizing the Basic-Translational Interface for Clinical Application; 2022 Jun 23-26; Boston, MA. Philadelphia (PA): AACR; Blood Cancer Discov 2022;3(5\_Suppl):Abstract nr A38.},
issue = {5\_Supplement}
}
@article{nieDualRoleCD702022,
title = {The Dual Role of {{CD70}} in {{B-cell}} Lymphomagenesis},
author = {Nie, Man and Ren, Weicheng and Ye, Xiaofei and Berglund, Mattias and Wang, Xianhuo and Fjordén, Karin and Du, Likun and Giannoula, Yvonne and Lei, Dexin and Su, Wenjia and Li, Wei and Liu, Dongbing and Linderoth, Johan and Jiang, Chengyi and Bao, Huijing and Jiang, Wenqi and Huang, Huiqiang and Hou, Yong and Zhu, Shida and Enblad, Gunilla and Jerkeman, Mats and Wu, Kui and Zhang, Huilai and Amini, Rose-Marie and Li, Zhi-Ming and Pan-Hammarström, Qiang},
date = {2022-12},
journaltitle = {Clinical and Translational Medicine},
shortjournal = {Clin Transl Med},
volume = {12},
number = {12},
eprint = {36471481},
eprinttype = {pmid},
pages = {e1118},
issn = {2001-1326},
doi = {10.1002/ctm2.1118},
abstract = {BACKGROUND: CD70 is a costimulatory molecule that is transiently expressed on a small set of activated lymphocytes and is involved in T-cell-mediated immunity. However, the role of CD70 in B-cell malignancies remains controversial. METHODS: We investigated the clinical relevance of CD70 genetic alterations and its protein expression in two diffuse large B-cell lymphoma (DLBCL) cohorts with different ethnic backgrounds. We also performed transcriptomic analysis to explore the role of CD70 alterations in tumour microenvironment. We further tested the blockade of CD70 in combination with PD-L1 inhibitor in a murine lymphoma model. RESULTS: We showed that CD70 genetic aberrations occurred more frequently in the Chinese DLBCL cohort (56/233, 24.0\%) than in the Swedish cohort (9/84, 10.8\%), especially in those with concomitant hepatitis B virus (HBV) infection. The CD70 genetic changes in DLBCL resulted in a reduction/loss of protein expression and/or CD27 binding, which might impair T cell priming and were independently associated with poor overall survival. Paradoxically, we observed that over-expression of CD70 protein was also associated with a poor treatment response, as well as an advanced disease stage and EBV infection. More exhausted CD8+ T cells were furthermore identified in CD70 high-expression DLBCLs. Finally, in a murine lymphoma model, we demonstrated that blocking the CD70/CD27 and/or PD1/PD-L1 interactions could reduce CD70+ lymphoma growth in vivo, by directly impairing the tumour cell proliferation and rescuing the exhausted T cells. CONCLUSIONS: Our findings suggest that CD70 can play a role in either tumour suppression or oncogenesis in DLBCL, likely via distinct immune evasion mechanisms, that is, impairing T cell priming or inducing T cell exhaustion. Characterisation of specific dysfunction of CD70 in DLBCL may thus provide opportunities for the development of novel targeted immuno-therapeutic strategies.},
langid = {english},
pmcid = {PMC9722974},
keywords = {Animals,B-Lymphocytes,CD27 Ligand,CD70,CD8-Positive T-Lymphocytes,diffuse large B-cell lymphoma,Epstein-Barr Virus Infections,genetic aberration,HBV infection,Humans,immune evasion,Lymphoma Large B-Cell Diffuse,Mice,Tumor Microenvironment}
}
@article{abateDistinctViralMutational2015,
title = {Distinct {{Viral}} and {{Mutational Spectrum}} of {{Endemic Burkitt Lymphoma}}},
author = {Abate, F. and Ambrosio, M. and Mundo, L. and Laginestra, M. and Fuligni, F. and Rossi, M. and Zairis, Sakellarios and Gazaneo, Sara and Falco, G. De and Lazzi, S. and Bellan, C. and Rocca, B. J. and Amato, T. and Marasco, E. and Etebari, Maryam and Ogwang, M. and Calbi, V. and Ndede, I. and Patel, K. and Chumba, D. and Piccaluga, P. and Pileri, S. and Leoncini, L. and Rabadán, R.},
date = {2015},
journaltitle = {PLoS Pathogens},
shortjournal = {PLoS Pathogens},
volume = {11},
doi = {10.1371/journal.ppat.1005158}
}
@article{agarwalDynamicMolecularMonitoring2019,
title = {Dynamic Molecular Monitoring Reveals That {{SWI}}–{{SNF}} Mutations Mediate Resistance to Ibrutinib plus Venetoclax in Mantle Cell Lymphoma},
author = {Agarwal, Rishu and Chan, Yih-Chih and Tam, Constantine S. and Hunter, Tane and Vassiliadis, Dane and Teh, Charis E. and Thijssen, Rachel and Yeh, Paul and Wong, Stephen Q. and Ftouni, Sarah and Lam, Enid Y. N. and Anderson, Mary Ann and Pott, Christiane and Gilan, Omer and Bell, Charles C. and Knezevic, Kathy and Blombery, Piers and Rayeroux, Kathleen and Zordan, Adrian and Li, Jason and Huang, David C. S. and Wall, Meaghan and Seymour, John F. and Gray, Daniel H. D. and Roberts, Andrew W. and Dawson, Mark A. and Dawson, Sarah-Jane},
date = {2019-01},
journaltitle = {Nature Medicine},
volume = {25},
number = {1},
pages = {119--129},
issn = {1546-170X},
doi = {10.1038/s41591-018-0243-z},
abstract = {Molecular alterations in ctDNA of patients with mantle cell lymphoma uncovers mutations in SWI–SNF associated with resistance to ibrutinib and venetoclax combination and provide a rationale for restoring sensitivity through Bcl-xL inhibition.},
langid = {english}
}
@article{ahmadiMYCMultipurposeOncogene2021,
title = {{{MYC}}: A Multipurpose Oncogene with Prognostic and Therapeutic Implications in Blood Malignancies},
shorttitle = {{{MYC}}},
author = {Ahmadi, Seyed Esmaeil and Rahimi, Samira and Zarandi, Bahman and Chegeni, Rouzbeh and Safa, Majid},
date = {2021-08-09},
journaltitle = {Journal of Hematology \& Oncology},
shortjournal = {Journal of Hematology \& Oncology},
volume = {14},
number = {1},
pages = {121},
issn = {1756-8722},
doi = {10.1186/s13045-021-01111-4},
abstract = {MYC oncogene is a transcription factor with a wide array of functions affecting cellular activities such as cell cycle, apoptosis, DNA damage response, and hematopoiesis. Due to the multi-functionality of MYC, its expression is regulated at multiple levels. Deregulation of this oncogene can give rise to a variety of cancers. In this review, MYC regulation and the mechanisms by which MYC adjusts cellular functions and its implication in hematologic malignancies are summarized. Further, we also discuss potential inhibitors of MYC that could be beneficial for treating hematologic malignancies.},
keywords = {Apoptosis,Cell cycle,DNA damage response,Hematological malignancies,MYC,Oncogene,Prognostic importance,Regulation,Therapeutic implications}
}
@article{akhoondiFBXW7HCDC4General2007,
title = {{{FBXW7}}/{{hCDC4 Is}} a {{General Tumor Suppressor}} in {{Human Cancer}}},
author = {Akhoondi, Shahab and Sun, Dahui and family=Lehr, given=Natalie, prefix=von der, useprefix=false and Apostolidou, Sophia and Klotz, Kathleen and Maljukova, Alena and Cepeda, Diana and Fiegl, Heidi and Dofou, Dimitra and Marth, Christian and Mueller-Holzner, Elisabeth and Corcoran, Martin and Dagnell, Markus and Nejad, Sepideh Zabihi and Nayer, Babak Noori and Zali, Mohammad Reza and Hansson, Johan and Egyhazi, Susanne and Petersson, Fredrik and Sangfelt, Per and Nordgren, Hans and Grander, Dan and Reed, Steven I. and Widschwendter, Martin and Sangfelt, Olle and Spruck, Charles},
date = {2007-10-01},
journaltitle = {Cancer Research},
shortjournal = {Cancer Res},
volume = {67},
number = {19},
eprint = {17909001},
eprinttype = {pmid},
pages = {9006--9012},
publisher = {American Association for Cancer Research},
issn = {0008-5472, 1538-7445},
doi = {10.1158/0008-5472.CAN-07-1320},
abstract = {The ubiquitin-proteasome system is a major regulatory pathway of protein degradation and plays an important role in cellular division. Fbxw7 (or hCdc4), a member of the F-box family of proteins, which are substrate recognition components of the multisubunit ubiquitin ligase SCF (Skp1-Cdc53/Cullin-F-box-protein), has been shown to mediate the ubiquitin-dependent proteolysis of several oncoproteins including cyclin E1, c-Myc, c-Jun, and Notch. The oncogenic potential of Fbxw7 substrates, frequent allelic loss in human cancers, and demonstration that mutation of FBXW7 cooperates with p53 in mouse tumorigenesis have suggested that Fbxw7 could function as a tumor suppressor in human cancer. Here, we carry out an extensive genetic screen of primary tumors to evaluate the role of FBXW7 as a tumor suppressor in human tumorigenesis. Our results indicate that FBXW7 is inactivated by mutation in diverse human cancer types with an overall mutation frequency of ∼6\%. The highest mutation frequencies were found in tumors of the bile duct (cholangiocarcinomas, 35\%), blood (T-cell acute lymphocytic leukemia, 31\%), endometrium (9\%), colon (9\%), and stomach (6\%). Approximately 43\% of all mutations occur at two mutational “hotspots,” which alter Arg residues (Arg465 and Arg479) that are critical for substrate recognition. Furthermore, we show that Fbxw7Arg465 hotspot mutant can abrogate wild-type Fbxw7 function through a dominant negative mechanism. Our study is the first comprehensive screen of FBXW7 mutations in various human malignancies and shows that FBXW7 is a general tumor suppressor in human cancer. [Cancer Res 2007;67(19):9006–12]},
langid = {english}
}
@article{albuquerqueEnhancingKnowledgeDiscovery2017,
title = {Enhancing Knowledge Discovery from Cancer Genomics Data with {{Galaxy}}},
author = {Albuquerque, Marco A. and Grande, Bruno M. and Ritch, Elie J. and Pararajalingam, Prasath and Jessa, Selin and Krzywinski, Martin and Grewal, Jasleen K. and Shah, Sohrab P. and Boutros, Paul C. and Morin, Ryan D.},
date = {2017-05-01},
journaltitle = {GigaScience},
shortjournal = {Gigascience},
volume = {6},
number = {5},
eprint = {28327945},
eprinttype = {pmid},
pages = {1--13},
issn = {2047-217X},
doi = {10.1093/gigascience/gix015},
abstract = {The field of cancer genomics has demonstrated the power of massively parallel sequencing techniques to inform on the genes and specific alterations that drive tumor onset and progression. Although large comprehensive sequence data sets continue to be made increasingly available, data analysis remains an ongoing challenge, particularly for laboratories lacking dedicated resources and bioinformatics expertise. To address this, we have produced a collection of Galaxy tools that represent many popular algorithms for detecting somatic genetic alterations from cancer genome and exome data. We developed new methods for parallelization of these tools within Galaxy to accelerate runtime and have demonstrated their usability and summarized their runtimes on multiple cloud service providers. Some tools represent extensions or refinement of existing toolkits to yield visualizations suited to cohort-wide cancer genomic analysis. For example, we present Oncocircos and Oncoprintplus, which generate data-rich summaries of exome-derived somatic mutation. Workflows that integrate these to achieve data integration and visualizations are demonstrated on a cohort of 96 diffuse large B-cell lymphomas and enabled the discovery of multiple candidate lymphoma-related genes. Our toolkit is available from our GitHub repository as Galaxy tool and dependency definitions and has been deployed using virtualization on multiple platforms including Docker.},
langid = {english},
pmcid = {PMC5437943},
keywords = {Algorithms,Cancer,Cloud,Driver,Genome,Genomics,Humans,Internet,Lymphoma,Lymphoma Large B-Cell Diffuse,Mutation,Pipeline,Software,Tool,Workflow}
}
@article{alkallasMultiomicAnalysisReveals2020,
title = {Multi-Omic Analysis Reveals Significantly Mutated Genes and {{DDX3X}} as a Sex-Specific Tumor Suppressor in Cutaneous Melanoma},
author = {Alkallas, Rached and Lajoie, Mathieu and Moldoveanu, Dan and Hoang, Karen Vo and Lefrançois, Philippe and Lingrand, Marine and Ahanfeshar-Adams, Mozhdeh and Watters, Kevin and Spatz, Alan and Zippin, Jonathan H. and Najafabadi, Hamed S. and Watson, Ian R.},
date = {2020-06},
journaltitle = {Nature Cancer},
shortjournal = {Nat Cancer},
volume = {1},
number = {6},
pages = {635--652},
publisher = {Nature Publishing Group},
issn = {2662-1347},
doi = {10.1038/s43018-020-0077-8},
abstract = {The high background tumor mutation burden in cutaneous melanoma limits the ability to identify significantly mutated genes (SMGs) that drive this cancer. To address this, we performed a mutation significance study of over 1,000 melanoma exomes, combined with a multi-omic analysis of 470 cases from The Cancer Genome Atlas. We discovered several SMGs with co-occurring loss-of-heterozygosity and loss-of-function mutations, including PBRM1, PLXNC1 and PRKAR1A, which encodes a protein kinase A holoenzyme subunit. Deconvolution of bulk tumor transcriptomes into cancer, immune and stromal components revealed a melanoma-intrinsic oxidative phosphorylation signature associated with protein kinase A pathway alterations. We also identified SMGs on the X chromosome, including the RNA helicase DDX3X, whose loss-of-function mutations were exclusively observed in males. Finally, we found that tumor mutation burden and immune infiltration contain complementary information on survival of patients with melanoma. In summary, our multi-omic analysis provides insights into melanoma etiology and supports contribution of specific mutations to the sex bias observed in this cancer.},
issue = {6},
langid = {english}
}
@article{ankoGlobalAnalysisReveals2010,
title = {Global Analysis Reveals {{SRp20-}} and {{SRp75-specific mRNPs}} in Cycling and Neural Cells},
author = {Ankö, Minna-Liisa and Morales, Lucia and Henry, Ian and Beyer, Andreas and Neugebauer, Karla M.},
date = {2010-08},
journaltitle = {Nature Structural \& Molecular Biology},
shortjournal = {Nat. Struct. Mol. Biol.},
volume = {17},
number = {8},
eprint = {20639886},
eprinttype = {pmid},
pages = {962--970},
issn = {1545-9985},
doi = {10.1038/nsmb.1862},
abstract = {Members of the SR protein family of RNA-binding proteins have numerous roles in mRNA metabolism, from transcription to translation. To understand how SR proteins coordinate gene regulation, comprehensive knowledge of endogenous mRNA targets is needed. Here we establish physiological expression of GFP-tagged SR proteins from stable transgenes. Using the GFP tag for immunopurification of mRNPs, mRNA targets of SRp20 and SRp75 were identified in cycling and neurally induced P19 cells. Genome-wide analysis showed that SRp20 and SRp75 associate with hundreds of distinct, functionally related groups of transcripts that change in response to neural differentiation. Knockdown of either SRp20 or SRp75 led to up- or downregulation of specific transcripts, including identified targets, and rescue by the GFP-tagged SR proteins proved their functionality. Thus, SR proteins contribute to the execution of gene-expression programs through their association with distinct endogenous mRNAs.},
langid = {english},
keywords = {Animals,Cell Cycle,Cell Differentiation,Cell Line Tumor,Chromosomes Artificial Bacterial,Gene Expression Regulation Neoplastic,Gene Knockdown Techniques,Green Fluorescent Proteins,Immunoprecipitation,Mice,Neurons,Organ Specificity,Protein Binding,Ribonucleoproteins,RNA Messenger,RNA-Binding Proteins,Serine-Arginine Splicing Factors}
}
@article{ankoRNAbindingLandscapesTwo2012,
title = {The {{RNA-binding}} Landscapes of Two {{SR}} Proteins Reveal Unique Functions and Binding to Diverse {{RNA}} Classes},
author = {Änkö, Minna-Liisa and Müller-McNicoll, Michaela and Brandl, Holger and Curk, Tomaz and Gorup, Crtomir and Henry, Ian and Ule, Jernej and Neugebauer, Karla M.},
date = {2012},
journaltitle = {Genome Biology},
shortjournal = {Genome Biol.},
volume = {13},
number = {3},
eprint = {22436691},
eprinttype = {pmid},
pages = {R17},
issn = {1474-760X},
doi = {10.1186/gb-2012-13-3-r17},
abstract = {BACKGROUND: The SR proteins comprise a family of essential, structurally related RNA binding proteins. The complexity of their RNA targets and specificity of RNA recognition in vivo is not well understood. Here we use iCLIP to globally analyze and compare the RNA binding properties of two SR proteins, SRSF3 and SRSF4, in murine cells. RESULTS: SRSF3 and SRSF4 binding sites mapped to largely non-overlapping target genes, and in vivo consensus binding motifs were distinct. Interactions with intronless and intron-containing mRNAs as well as non-coding RNAs were detected. Surprisingly, both SR proteins bound to the 3' ends of the majority of intronless histone transcripts, implicating SRSF3 and SRSF4 in histone mRNA metabolism. In contrast, SRSF3 but not SRSF4 specifically bound transcripts encoding numerous RNA binding proteins. Remarkably, SRSF3 was shown to modulate alternative splicing of its own as well as three other transcripts encoding SR proteins. These SRSF3-mediated splicing events led to downregulation of heterologous SR proteins via nonsense-mediated decay. CONCLUSIONS: SRSF3 and SRSF4 display unique RNA binding properties underlying diverse cellular regulatory mechanisms, with shared as well as unique coding and non-coding targets. Importantly, CLIP analysis led to the discovery that SRSF3 cross-regulates the expression of other SR protein family members.},
langid = {english},
pmcid = {PMC3439968},
keywords = {3' Untranslated Regions,Alternative Splicing,Animals,Binding Sites,Cell Line Tumor,Gene Expression Regulation,Histones,Introns,Mice,RNA Untranslated,RNA-Binding Proteins,Serine-Arginine Splicing Factors}
}
@article{ansa-addoRNABindingProtein2020,
title = {{{RNA}} Binding Protein {{PCBP1}} Is an Intracellular Immune Checkpoint for Shaping {{T}} Cell Responses in Cancer Immunity},
author = {Ansa-Addo, Ephraim A. and Huang, Huai-Cheng and Riesenberg, Brian and Iamsawat, Supinya and Borucki, Davis and Nelson, Michelle H. and Nam, Jin Hyun and Chung, Dongjun and Paulos, Chrystal M. and Liu, Bei and Yu, Xue-Zhong and Philpott, Caroline and Howe, Philip H. and Li, Zihai},
date = {2020-05-29},
journaltitle = {Science Advances},
shortjournal = {Sci Adv},
volume = {6},
number = {22},
eprint = {32523987},
eprinttype = {pmid},
pages = {eaaz3865},
issn = {2375-2548},
doi = {10.1126/sciadv.aaz3865},
abstract = {RNA binding protein PCBP1 guards effector and antitumor T cell functions., Distinct lineages of T cells can act in response to various environmental cues to either drive or restrict immune-mediated pathology. Here, we identify the RNA binding protein, poly(C)-binding protein 1 (PCBP1) as an intracellular immune checkpoint that is up-regulated in activated T cells to prevent conversion of effector T (Teff) cells into regulatory T (Treg) cells, by restricting the expression of Teff cell–intrinsic Treg commitment programs. This was critical for stabilizing Teff cell functions and subverting immune-suppressive signals. T cell–specific deletion of Pcbp1 favored Treg cell differentiation, enlisted multiple inhibitory immune checkpoint molecules including PD-1, TIGIT, and VISTA on tumor-infiltrating lymphocytes, and blunted antitumor immunity. Our results demonstrate a critical role for PCBP1 as an intracellular immune checkpoint for maintaining Teff cell functions in cancer immunity.},
pmcid = {PMC7259945}
}
@article{arthurGenomewideDiscoverySomatic2018,
title = {Genome-Wide Discovery of Somatic Regulatory Variants in Diffuse Large {{B-cell}} Lymphoma},
author = {Arthur, Sarah E. and Jiang, Aixiang and Grande, Bruno M. and Alcaide, Miguel and Cojocaru, Razvan and Rushton, Christopher K. and Mottok, Anja and Hilton, Laura K. and Lat, Prince Kumar and Zhao, Eric Y. and Culibrk, Luka and Ennishi, Daisuke and Jessa, Selin and Chong, Lauren and Thomas, Nicole and Pararajalingam, Prasath and Meissner, Barbara and Boyle, Merrill and Davidson, Jordan and Bushell, Kevin R. and Lai, Daniel and Farinha, Pedro and Slack, Graham W. and Morin, Gregg B. and Shah, Sohrab and Sen, Dipankar and Jones, Steven J. M. and Mungall, Andrew J. and Gascoyne, Randy D. and Audas, Timothy E. and Unrau, Peter and Marra, Marco A. and Connors, Joseph M. and Steidl, Christian and Scott, David W. and Morin, Ryan D.},
date = {2018-10-01},
journaltitle = {Nature Communications},
shortjournal = {Nat Commun},
volume = {9},
number = {1},
eprint = {30275490},
eprinttype = {pmid},
pages = {4001},
issn = {2041-1723},
doi = {10.1038/s41467-018-06354-3},
abstract = {Diffuse large B-cell lymphoma (DLBCL) is an aggressive cancer originating from mature B-cells. Prognosis is strongly associated with molecular subgroup, although the driver mutations that distinguish the two main subgroups remain poorly defined. Through an integrative analysis of whole genomes, exomes, and transcriptomes, we have uncovered genes and non-coding loci that are commonly mutated in DLBCL. Our analysis has identified novel cis-regulatory sites, and implicates recurrent mutations in the 3' UTR of NFKBIZ as a novel mechanism of oncogene deregulation and NF-κB pathway activation in the activated B-cell (ABC) subgroup. Small amplifications associated with over-expression of FCGR2B (the Fcγ receptor protein IIB), primarily in the germinal centre B-cell (GCB) subgroup, correlate with poor patient outcomes suggestive of a novel oncogene. These results expand the list of subgroup driver mutations that may facilitate implementation of improved diagnostic assays and could offer new avenues for the development of targeted therapeutics.},
langid = {english},
pmcid = {PMC6167379},
keywords = {3' Untranslated Regions,Adaptor Proteins Signal Transducing,B-Lymphocytes,Cell Line Tumor,Exome,Gene Expression Regulation Neoplastic,Genes Regulator,Genetic Variation,Genome Human,Genome-Wide Association Study,Germinal Center,Humans,I-kappa B Proteins,Lymphoma Large B-Cell Diffuse,Mutation,Nuclear Proteins,Receptors IgG,Sequence Analysis DNA,Transcriptome}
}
@article{baohuaMutationsPIK3CAGene,
title = {Mutations of the {{PIK3CA Gene}} in {{Diffuse Large B Cell Lymphoma}}},
author = {Baohua, Yu and Xiaoyan, Zhou and Tiecheng, Zhang and Tao, Qin and Daren, Shi},
journaltitle = {Diagnostic Molecular Pathology},
volume = {17},
number = {3},
pages = {159--165}
}
@article{baoP53inducedLincRNAp21Derails2015,
title = {The P53-Induced {{lincRNA-p21}} Derails Somatic Cell Reprogramming by Sustaining {{H3K9me3}} and {{CpG}} Methylation at Pluripotency Gene Promoters},
author = {Bao, Xichen and Wu, Haitao and Zhu, Xihua and Guo, Xiangpeng and Hutchins, Andrew P. and Luo, Zhiwei and Song, Hong and Chen, Yongqiang and Lai, Keyu and Yin, Menghui and Xu, Lingxiao and Zhou, Liang and Chen, Jiekai and Wang, Dongye and Qin, Baoming and Frampton, Jon and Tse, Hung-Fat and Pei, Duanqing and Wang, Huating and Zhang, Biliang and Esteban, Miguel A.},
date = {2015-01},
journaltitle = {Cell Research},
shortjournal = {Cell Res},
volume = {25},
number = {1},
pages = {80--92},
publisher = {Nature Publishing Group},
issn = {1748-7838},
doi = {10.1038/cr.2014.165},
abstract = {Recent studies have boosted our understanding of long noncoding RNAs (lncRNAs) in numerous biological processes, but few have examined their roles in somatic cell reprogramming. Through expression profiling and functional screening, we have identified that the large intergenic noncoding RNA p21 (lincRNA-p21) impairs reprogramming. Notably, lincRNA-p21 is induced by p53 but does not promote apoptosis or cell senescence in reprogramming. Instead, lincRNA-p21 associates with the H3K9 methyltransferase SETDB1 and the maintenance DNA methyltransferase DNMT1, which is facilitated by the RNA-binding protein HNRNPK. Consequently, lincRNA-p21 prevents reprogramming by sustaining H3K9me3 and/or CpG methylation at pluripotency gene promoters. Our results provide insight into the role of lncRNAs in reprogramming and establish a novel link between p53 and heterochromatin regulation.},
issue = {1},
langid = {english},
keywords = {DNA methylation,Long non-coding RNAs,Reprogramming}
}
@article{barariaCathepsinAlterationsInduce2020,
title = {Cathepsin {{S Alterations Induce}} a {{Tumor-Promoting Immune Microenvironment}} in {{Follicular Lymphoma}}},
author = {Bararia, Deepak and Hildebrand, Johannes A. and Stolz, Sebastian and Haebe, Sarah and Alig, Stefan and Trevisani, Christopher P. and Osorio-Barrios, Francisco and Bartoschek, Michael D. and Mentz, Michael and Pastore, Alessandro and Gaitzsch, Erik and Heide, Michael and Jurinovic, Vindi and Rautter, Katharina and Gunawardana, Jay and Sabdia, Muhammed B. and Szczepanowski, Monika and Richter, Julia and Klapper, Wolfram and Louissaint, Abner and Ludwig, Christina and Bultmann, Sebastian and Leonhardt, Heinrich and Eustermann, Sebastian and Hopfner, Karl-Peter and Hiddemann, Wolfgang and family=Bergwelt-Baildon, given=Michael, prefix=von, useprefix=true and Steidl, Christian and Kridel, Robert and Tobin, Joshua W. D. and Gandhi, Maher K. and Weinstock, David M. and Schmidt-Supprian, Marc and Sárosi, Menyhárt B. and Rudelius, Martina and Passerini, Verena and Mautner, Josef and Weigert, Oliver},
date = {2020-05-05},
journaltitle = {Cell Reports},
shortjournal = {Cell Rep},
volume = {31},
number = {5},
eprint = {32330423},
eprinttype = {pmid},
pages = {107522},
issn = {2211-1247},
doi = {10.1016/j.celrep.2020.107522},
abstract = {Tumor cells orchestrate their microenvironment. Here, we provide biochemical, structural, functional, and clinical evidence that Cathepsin S (CTSS) alterations induce a tumor-promoting immune microenvironment in follicular lymphoma (FL). We found CTSS mutations at Y132 in 6\% of FL (19/305). Another 13\% (37/286) had CTSS amplification, which was associated with higher CTSS expression. CTSS Y132 mutations lead to accelerated autocatalytic conversion from an enzymatically inactive profrom to active CTSS and increased substrate cleavage, including CD74, which regulates major histocompatibility complex class II (MHC class II)-restricted antigen presentation. Lymphoma cells with hyperactive CTSS more efficiently activated antigen-specific CD4+ T~cells in~vitro. Tumors with hyperactive CTSS showed increased CD4+ T~cell infiltration and proinflammatory cytokine perturbation in a mouse model and in human FLs. In mice, this CTSS-induced immune microenvironment promoted tumor growth. Clinically, patients with CTSS-hyperactive FL had better treatment outcomes with standard immunochemotherapies, indicating that these immunosuppressive regimens target both the lymphoma cells and the tumor-promoting immune microenvironment.},
langid = {english},
keywords = {Animals,Antigen Presentation,antigen processing and presentation,Antigens Differentiation B-Lymphocyte,cathepsin S,Cathepsins,cysteine-protease,Cytokines,follicular lymphoma,Histocompatibility Antigens Class II,Humans,immune microenvironment,Immunosuppression Therapy,Lymphoma Follicular,Mice,T cell activation,Tumor Microenvironment}
}
@article{bassoBCL6MasterRegulator2010,
title = {{{BCL6}}: Master Regulator of the Germinal Center Reaction and Key Oncogene in {{B}} Cell Lymphomagenesis},
shorttitle = {{{BCL6}}},
author = {Basso, Katia and Dalla-Favera, Riccardo},
date = {2010},
journaltitle = {Advances in Immunology},
shortjournal = {Adv Immunol},
volume = {105},
eprint = {20510734},
eprinttype = {pmid},
pages = {193--210},
issn = {1557-8445},
doi = {10.1016/S0065-2776(10)05007-8},
abstract = {BCL6 is a transcriptional repressor which has emerged as a critical regulator of germinal centers (GC), the sites where B cells are selected based on the production of antibodies with high affinity for the antigen. BCL6 is also a frequently activated oncogene in the pathogenesis of human B cell lymphomas, most of which derive from the GC B cells. A thorough understanding of the biological role of BCL6 in normal B cell development and lymphomagenesis depends upon the identification of the full set of genes that are targets of its transcriptional regulatory function. Recently, the identification of BCL6 targets has been implemented with the use of genome-wide chromatin immunoprecipitation and gene expression profiling approaches. A large set of promoters have been shown to be physically bound by BCL6, but only a fraction of them appears to be subjected to transcriptional repression in GC B cells. This set of BCL6 targets points to a number of cellular functions which are likely to be directly controlled by BCL6 during GC development, including activation, survival, DNA-damage response, cell cycle arrest, cytokine-, toll-like receptor-, TGFbeta-, WNT-signaling, and differentiation. Overall, BCL6 is revealing its dual role of "safe-keeper" in preventing centroblasts from responding to signals leading to a premature exit from the GC and of contributor to lymphomagenesis by allowing the instauration of conditions favorable to malignant transformation.},
langid = {english},
keywords = {B-Lymphocytes,DNA-Binding Proteins,Germinal Center,Humans,Lymphocyte Activation,Lymphoma B-Cell,Proto-Oncogene Proteins c-bcl-6,Somatic Hypermutation Immunoglobulin}
}
@article{bassoRolesBCL6Normal2012,
title = {Roles of {{BCL6}} in Normal and Transformed Germinal Center {{B}} Cells},
author = {Basso, Katia and Dalla-Favera, Riccardo},
date = {2012-05},
journaltitle = {Immunological Reviews},
shortjournal = {Immunol Rev},
volume = {247},
number = {1},
eprint = {22500840},
eprinttype = {pmid},
pages = {172--183},
issn = {1600-065X},
doi = {10.1111/j.1600-065X.2012.01112.x},
abstract = {BCL6 is a transcriptional repressor required in mature B cells during the germinal center (GC) reaction. Multiple mechanisms act coordinately to timely modulate BCL6 expression at transcriptional and post-transcriptional levels. BCL6 prevents premature activation and differentiation of GC B cells and provides an environment tolerant of the DNA breaks associated with immunoglobulin gene remodeling mechanisms involved in the production of high-affinity antibodies of different isotypes. The critical functions exerted by BCL6 during normal B-cell development can be hijacked by the malignant transformation process. Indeed, BCL6 is targeted by genetic aberrations and acts as an oncogene in GC-derived lymphomas. The aberrations affecting BCL6 interfere with the multiple levels of regulation that grant a fine tuning of BCL6 expression and activity in physiologic conditions. This review summarizes the current knowledge on BCL6 function and its role in lymphomagenesis.},
langid = {english},
keywords = {Animals,B-Lymphocytes,Cell Differentiation,Cell Transformation Neoplastic,Germinal Center,Humans,Lymphoma Non-Hodgkin,Proto-Oncogene Proteins c-bcl-6,Transcriptional Activation}
}
@article{beaLandscapeSomaticMutations2013,
title = {Landscape of Somatic Mutations and Clonal Evolution in Mantle Cell Lymphoma},
author = {Beà, Sílvia and Valdés-Mas, Rafael and Navarro, Alba and Salaverria, Itziar and Martín-Garcia, David and Jares, Pedro and Giné, Eva and Pinyol, Magda and Royo, Cristina and Nadeu, Ferran and Conde, Laura and Juan, Manel and Clot, Guillem and Vizán, Pedro and Croce, Luciano Di and Puente, Diana A. and López-Guerra, Mónica and Moros, Alexandra and Roue, Gael and Aymerich, Marta and Villamor, Neus and Colomo, Lluís and Martínez, Antonio and Valera, Alexandra and Martín-Subero, José I. and Amador, Virginia and Hernández, Luis and Rozman, Maria and Enjuanes, Anna and Forcada, Pilar and Muntañola, Ana and Hartmann, Elena M. and Calasanz, María J. and Rosenwald, Andreas and Ott, German and Hernández-Rivas, Jesús M. and Klapper, Wolfram and Siebert, Reiner and Wiestner, Adrian and Wilson, Wyndham H. and Colomer, Dolors and López-Guillermo, Armando and López-Otín, Carlos and Puente, Xose S. and Campo, Elías},
year = {2013},
journaltitle = {Proceedings of the National Academy of Sciences},
shortjournal = {PNAS},
volume = {110},
number = {45},
eprint = {24145436},
eprinttype = {pmid},
pages = {18250--18255},
issn = {0027-8424, 1091-6490},
doi = {10.1073/pnas.1314608110},
abstract = {Mantle cell lymphoma (MCL) is an aggressive tumor, but a subset of patients may follow an indolent clinical course. To understand the mechanisms underlying this biological heterogeneity, we performed whole-genome and/or whole-exome sequencing on 29 MCL cases and their respective matched normal DNA, as well as 6 MCL cell lines. Recurrently mutated genes were investigated by targeted sequencing in an independent cohort of 172 MCL patients. We identified 25 significantly mutated genes, including known drivers such as ataxia-telangectasia mutated (ATM), cyclin D1 (CCND1), and the tumor suppressor TP53; mutated genes encoding the anti-apoptotic protein BIRC3 and Toll-like receptor 2 (TLR2); and the chromatin modifiers WHSC1, MLL2, and MEF2B. We also found NOTCH2 mutations as an alternative phenomenon to NOTCH1 mutations in aggressive tumors with a dismal prognosis. Analysis of two simultaneous or subsequent MCL samples by whole-genome/whole-exome (n = 8) or targeted (n = 19) sequencing revealed subclonal heterogeneity at diagnosis in samples from different topographic sites and modulation of the initial mutational profile at the progression of the disease. Some mutations were predominantly clonal or subclonal, indicating an early or late event in tumor evolution, respectively. Our study identifies molecular mechanisms contributing to MCL pathogenesis and offers potential targets for therapeutic intervention.},
langid = {english},
keywords = {cancer genetics,cancer heterogeneity,next-generation sequencing}
}
@article{behrensTranslationalSilencingFunction2018,
title = {A Translational Silencing Function of {{MCPIP1}}/{{Regnase-1}} Specified by the Target Site Context.},
author = {Behrens, Gesine and Winzen, Reinhard and Rehage, Nina and Dörrie, Anneke and Barsch, Monika and Hoffmann, Anne and Hackermüller, Jörg and Tiedje, Christopher and Heissmeyer, Vigo and Holtmann, Helmut},
date = {2018-02},
journaltitle = {Nucleic Acids Res},
volume = {10},
pages = {24}
}
@article{benhamouCMycMiR1792PTEN2018,
title = {The C-{{Myc}}/{{miR17-92}}/{{PTEN Axis Tunes PI3K Activity}} to {{Control Expression}} of {{Recombination Activating Genes}} in {{Early B Cell Development}}},
author = {Benhamou, David and Labi, Verena and Getahun, Andrew and Benchetrit, Eli and Dowery, Reem and Rajewsky, Klaus and Cambier, John C. and Melamed, Doron},
date = {2018},
journaltitle = {Frontiers in Immunology},
shortjournal = {Front Immunol},
volume = {9},
eprint = {30524445},
eprinttype = {pmid},
pages = {2715},
issn = {1664-3224},
doi = {10.3389/fimmu.2018.02715},
abstract = {Appropriate PI3K signals generated by the antigen receptor are essential to promote B cell development. Regulation of recombination activating gene (RAG)-1 and RAG-2 expression is one key process that is mediated by PI3K to ensure developmental progression and selection. When PI3K signals are too high or too low, expression of RAGs does not turn off and B cell development is impaired or blocked. Yet, the mechanism which tunes PI3K activity to control RAG expression during B cell development in the bone marrow is unknown. Recently we showed that a c-Myc/miR17-92/PTEN axis regulates PI3K activity for positive and negative selection of immature B cells. Here, we show that the c-Myc/miR17-92/PTEN axis tunes PI3K activity to control the expression of RAGs in proB cells. Using different genetically engineered mouse models we show that impaired function of the c-Myc/miR17-92/PTEN axis alters the PI3K/Akt/Foxo1 pathway to result in dis-regulated expression of RAG and a block in B cell development. Studies using 38c-13 B lymphoma cells, where RAGs are constitutively expressed, suggest that this regulatory effect is mediated post-translationally through Foxo1.},
langid = {english},
pmcid = {PMC6262168},
keywords = {B cell development,microRNA,PI3K–AKT pathway,PTEN (phosphatase and tensin homolog),recombination activating gene (RAG)}
}
@article{blenkGerminalCenterCelllike2007,
title = {Germinal Center {{B}} Cell-like ({{GCB}}) and Activated {{B}} Cell-like ({{ABC}}) Type of Diffuse Large {{B}} Cell Lymphoma ({{DLBCL}}): Analysis of Molecular Predictors, Signatures, Cell Cycle State and Patient Survival.},
author = {Blenk, S and Engelmann, J and Weniger, M and Schultz, J and Dittrich, M and Rosenwald, A and Muller-Hermelink, H K and Müller, T and Dandekar, T},
date = {2007},
journaltitle = {Cancer informatics},
volume = {3},
pages = {399--420}
}
@article{bohersTargetableActivatingMutations,
title = {Targetable Activating Mutations Are Very Frequent in {{GCB}} and {{ABC}} Diffuse Large {{B-cell}} Lymphoma.},
author = {Bohers, Elodie and Mareschal, Sylvain and Bouzelfen, Abdelilah and Marchand, Vinciane and Ruminy, Philippe and Maingonnat, Catherine and Ménard, Anne-Lise and Etancelin, Pascaline and Bertrand, Philippe and Dubois, Sydney and Alcantara, Marion and Bastard, Christian and Tilly, Hervé and Jardin, Fabrice},
journaltitle = {Genes Chromosome Canc},
volume = {53},
number = {2},
pages = {144--153}
}
@article{bohleRoleEarlyBcell2013,
title = {Role of Early {{B-cell}} Factor 1 ({{EBF1}}) in {{Hodgkin}} Lymphoma},
author = {Bohle, V. and Döring, C. and Hansmann, M.-L. and Küppers, R.},
date = {2013-03},
journaltitle = {Leukemia},
shortjournal = {Leukemia},
volume = {27},
number = {3},
eprint = {23174882},
eprinttype = {pmid},
pages = {671--679},
issn = {1476-5551},
doi = {10.1038/leu.2012.280},
abstract = {A hallmark of classical Hodgkin lymphoma (cHL) is that the B-cell-derived Hodgkin and Reed-Sternberg (HRS) tumor cells have largely lost the B-cell-typical gene expression program. The factors causing this 'reprogramming' of HRS cells are only partly understood. As early B-cell factor 1 (EBF1), a major B-cell transcription factor, is downregulated in HRS cells, we analyzed whether this downregulation contributes to the lost B-cell phenotype and tested the consequences of EBF1 re-expression in cHL cell lines. EBF1 re-expression caused an upregulation of B-cell genes, such as CD19, CD79A and CD79B, although the B-cell genes FOXO1 and PAX5 remained lowly expressed. The re-expression of CD19, CD79A and CD79B occurred largely without demethylation of promoter CpG motifs of these genes. In the cHL cell line L-1236 fitness decreased after EBF1 re-expression. These data show that EBF1 has the ability to reintroduce part of the B-cell signature in cHL cell lines. Loss of EBF1 expression in HRS cells therefore contributes to their lost B-cell phenotype. Notably, in the cHL cell line KM-H2 destructive mutations were found in one allele of EBF1, indicating that genetic lesions may sometimes have a role in impairing EBF1 expression.},
langid = {english},
keywords = {Apoptosis,B-Lymphocytes,Base Sequence,Biomarkers Tumor,Blotting Western,Cell Proliferation,CpG Islands,DNA Methylation,Gene Expression Profiling,Gene Expression Regulation Neoplastic,Hodgkin Disease,Humans,Molecular Sequence Data,Oligonucleotide Array Sequence Analysis,Promoter Regions Genetic,Real-Time Polymerase Chain Reaction,Reed-Sternberg Cells,Reverse Transcriptase Polymerase Chain Reaction,RNA Messenger,Sequence Homology Nucleic Acid,Trans-Activators}
}
@article{bothamSmallMoleculeProcaspase3Activation2016,
title = {Small-{{Molecule Procaspase-3 Activation Sensitizes Cancer}} to {{Treatment}} with {{Diverse Chemotherapeutics}}},
author = {Botham, Rachel C. and Roth, Howard S. and Book, Alison P. and Roady, Patrick J. and Fan, Timothy M. and Hergenrother, Paul J.},
date = {2016-08-24},
journaltitle = {ACS central science},
shortjournal = {ACS Cent Sci},
volume = {2},
number = {8},
eprint = {27610416},
eprinttype = {pmid},
pages = {545--559},
issn = {2374-7943},
doi = {10.1021/acscentsci.6b00165},
abstract = {Conventional chemotherapeutics remain essential treatments for most cancers, but their combination with other anticancer drugs (including targeted therapeutics) is often complicated by unpredictable synergies and multiplicative toxicities. As cytotoxic anticancer chemotherapeutics generally function through induction of apoptosis, we hypothesized that a molecularly targeted small molecule capable of facilitating a central and defining step in the apoptotic cascade, the activation of procaspase-3 to caspase-3, would broadly and predictably enhance activity of cytotoxic drugs. Here we show that procaspase-activating compound 1 (PAC-1) enhances cancer cell death induced by 15 different FDA-approved chemotherapeutics, across many cancer types and chemotherapeutic targets. In particular, the promising combination of PAC-1 and doxorubicin induces a synergistic reduction in tumor burden and enhances survival in murine tumor models of osteosarcoma and lymphoma. This PAC-1/doxorubicin combination was evaluated in 10 pet dogs with naturally occurring metastatic osteosarcoma or lymphoma, eliciting a biologic response in 3 of 6 osteosarcoma patients and 4 of 4 lymphoma patients. Importantly, in both mice and dogs, coadministration of PAC-1 with doxorubicin resulted in no additional toxicity. On the basis of the mode of action of PAC-1 and the high expression of procaspase-3 in many cancers, these results suggest the combination of PAC-1 with cytotoxic anticancer drugs as a potent and general strategy to enhance therapeutic response.},
langid = {english},
pmcid = {PMC4999974}
}
@article{bowlerMisidentificationMLL3Other2019,
title = {Misidentification of {{MLL3}} and Other Mutations in Cancer Due to Highly Homologous Genomic Regions},
author = {Bowler, Timothy G. and Pradhan, Kith and Kong, Yu and Bartenstein, Matthias and Morrone, Kerry A. and Sridharan, Ashwin and Kessel, Rachel M. and Shastri, Aditi and Giricz, Orsi and Bhagat, Tushar D. and Gordon-Mitchell, Shanisha and Rohanizadegan, Mersedeh and Hooda, Lauren and Datt, Ishan and Przychodzen, Bartlomiej P. and Parmar, Simrit and Maqbool, Shahina and Maciejewski, Jaroslaw P. and Steidl, Ulrich and Greally, John M. and Verma, Amit},
date = {2019-12},
journaltitle = {Leukemia \& Lymphoma},
shortjournal = {Leuk Lymphoma},
volume = {60},
number = {13},
eprint = {31288594},
eprinttype = {pmid},
pages = {3132--3137},
issn = {1029-2403},
doi = {10.1080/10428194.2019.1630620},
abstract = {The MLL3 gene has been shown to be recurrently mutated in many malignancies including in families with acute myeloid leukemia. We demonstrate that many MLL3 variant calls made by exome sequencing are false positives due to misalignment to homologous regions, including a region on chr21, and can only be validated by long-range PCR. Numerous other recurrently mutated genes reported in COSMIC and TCGA databases have pseudogenes and cannot also be validated by conventional short read-based sequencing approaches. Genome-wide identification of pseudogene regions demonstrates that frequency of these homologous regions is increased with sequencing read lengths below 200~bps. To enable identification of poor quality sequencing variants in prospective studies, we generated novel genome-wide maps of regions with poor mappability that can be used in variant calling algorithms. Taken together, our findings reveal that pseudogene regions are a source of false-positive mutations in cancers.},
langid = {english},
keywords = {Algorithms,AML,Chromosome Mapping,Databases Genetic,DNA Mutational Analysis,DNA-Binding Proteins,Exons,False Positive Reactions,High-Throughput Nucleotide Sequencing,Humans,Leukemia Myeloid Acute,MLL3,pseudogenes,Pseudogenes,Sequence Homology Nucleic Acid,Whole Exome Sequencing}
}
@article{bradyMCPIP1Zc3h12aKeeps2013,
title = {{{MCPIP1}} ({{Zc3h12a}}) Keeps Inflammation in Check by Cleaving 3|[Prime]| {{UTRs}}},
author = {Brady, Brenna L and Muljo, Stefan A},
date = {2013-05},
journaltitle = {Immunology and cell biology},
volume = {91},
number = {5},
pages = {331--332}
}
@article{braggioGenomicAnalysisMarginal2012,
title = {Genomic Analysis of Marginal Zone and Lymphoplasmacytic Lymphomas Identified Common and Disease-Specific Abnormalities},
author = {Braggio, Esteban and Dogan, Ahmet and Keats, Jonathan J. and Chng, Wee J. and Huang, Gaofeng and Matthews, Julie M. and Maurer, Matthew J. and Law, Mark E. and Bosler, David S. and Barrett, Michael and Lossos, Izidore S. and Witzig, Thomas E. and Fonseca, Rafael},
date = {2012-05},
journaltitle = {Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc},
shortjournal = {Mod Pathol},
volume = {25},
number = {5},
eprint = {22301699},
eprinttype = {pmid},
pages = {651--660},
issn = {1530-0285},
doi = {10.1038/modpathol.2011.213},
abstract = {Lymphoplasmacytic lymphomas and marginal zone lymphomas of nodal, extra-nodal and splenic types account for 10\% of non-Hodgkin lymphomas. They are similar at the cell differentiation level, sometimes making difficult to distinguish them from other indolent non-Hodgkin lymphomas. To better characterize their genetic basis, we performed array-based comparative genomic hybridization in 101 marginal zone lymphomas (46 MALT, 35 splenic and 20 nodal marginal zone lymphomas) and 13 lymphoplasmacytic lymphomas. Overall, 90\% exhibited copy-number abnormalities. Lymphoplasmacytic lymphomas demonstrated the most complex karyotype (median=7 copy-number abnormalities), followed by MALT (4), nodal (3.5) and splenic marginal zone lymphomas (3). A comparative analysis exposed a group of copy-number abnormalities shared by several or all the entities with few disease-specific abnormalities. Gain of chromosomes 3, 12 and 18 and loss of 6q23-q24 (TNFAIP3) were identified in all entities. Losses of 13q14.3 (MIRN15A-MIRN16-1) and 17p13.3-p12 (TP53) were found in lymphoplasmacytic and splenic marginal zone lymphomas; loss of 11q21-q22 (ATM) was found in nodal, splenic marginal zone and lymphoplasmacytic lymphomas and loss of 7q32.1-q33 was found in MALT, splenic and lymphoplasmacytic lymphomas. Abnormalities affecting the nuclear factor kappa B pathway were observed in 70\% of MALT and lymphoplasmacytic lymphomas and 30\% of splenic and nodal marginal zone lymphomas, suggesting distinct roles of this pathway in the pathogenesis/progression of these subtypes. Elucidation of the genetic alterations contributing to the pathogenesis of these lymphomas may guide to design-specific therapeutic approaches.},
langid = {english},
pmcid = {PMC3341516},
keywords = {Chromosome Aberrations,DNA Neoplasm,Gene Expression Profiling,Gene Expression Regulation Neoplastic,Genomics,Humans,In Situ Hybridization Fluorescence,Lymph Nodes,Lymphoma B-Cell Marginal Zone,Waldenstrom Macroglobulinemia}
}
@article{burkhardtClinicalRelevanceMolecular2022,
title = {Clinical Relevance of Molecular Characteristics in {{Burkitt}} Lymphoma Differs According to Age},
author = {Burkhardt, Birgit and Michgehl, Ulf and Rohde, Jonas and Erdmann, Tabea and Berning, Philipp and Reutter, Katrin and Rohde, Marius and Borkhardt, Arndt and Burmeister, Thomas and Dave, Sandeep and Tzankov, Alexandar and Dugas, Martin and Sandmann, Sarah and Fend, Falko and Finger, Jasmin and Mueller, Stephanie and Gökbuget, Nicola and Haferlach, Torsten and Kern, Wolfgang and Hartmann, Wolfgang and Klapper, Wolfram and Oschlies, Ilske and Richter, Julia and Kontny, Udo and Lutz, Mathias and Maecker-Kolhoff, Britta and Ott, German and Rosenwald, Andreas and Siebert, Reiner and family=Stackelberg, given=Arend, prefix=von, useprefix=true and Strahm, Brigitte and Woessmann, Wilhelm and Zimmermann, Martin and Zapukhlyak, Myroslav and Grau, Michael and Lenz, Georg},
date = {2022-07-06},
journaltitle = {Nature Communications},
shortjournal = {Nat Commun},
volume = {13},
number = {1},
eprint = {35794096},
eprinttype = {pmid},
pages = {3881},
issn = {2041-1723},
doi = {10.1038/s41467-022-31355-8},
abstract = {While survival has improved for Burkitt lymphoma patients, potential differences in outcome between pediatric and adult patients remain unclear. In both age groups, survival remains poor at relapse. Therefore, we conducted a comparative study in a large pediatric cohort, including 191 cases and 97 samples from adults. While TP53 and CCND3 mutation frequencies are not age related, samples from pediatric patients showed a higher frequency of mutations in ID3, DDX3X, ARID1A and SMARCA4, while several genes such as BCL2 and YY1AP1 are almost exclusively mutated in adult patients. An unbiased analysis reveals a transition of the mutational profile between 25 and 40 years of age. Survival analysis in the pediatric cohort confirms that TP53 mutations are significantly associated with higher incidence of relapse (25\,±\,4\% versus 6\,±\,2\%, p-value 0.0002). This identifies a promising molecular marker for relapse incidence in pediatric BL which will be used in future clinical trials.},
langid = {english},
pmcid = {PMC9259584},
keywords = {Adult,Burkitt Lymphoma,Cell Cycle Proteins,Child,DNA Helicases,Genes cdc,Humans,Mutation,Mutation Rate,Neoplasm Recurrence Local,Nuclear Proteins,Transcription Factors}
}
@article{carlottiTransformationFollicularLymphoma,
title = {Transformation of Follicular Lymphoma to Diffuse Large {{B-cell}} Lymphoma May Occur by Divergent Evolution from a Common Progenitor Cell or by Direct Evolution from the Follicular Lymphoma Clone.},
author = {Carlotti, Emanuela and Wrench, David and Matthews, Janet and Iqbal, Sameena and Davies, Andrew and Norton, Andrew and Hart, Jason and Lai, Raymond and Montoto, Silvia and Gribben, John G and Lister, T Andrew and Fitzgibbon, Jude},
journaltitle = {Blood},
volume = {113},
number = {15},
pages = {3553--3557}
}
@article{chapuyDiscoveryCharacterizationSuperEnhancerAssociated2013,
title = {Discovery and {{Characterization}} of {{Super-Enhancer-Associated Dependencies}} in {{Diffuse Large B Cell Lymphoma}}},
author = {Chapuy, Bjoern and McKeown, Michael R and Lin, Charles Y and Monti, Stefano and Roemer, Margaretha G M and Qi, Jun and Rahl, Peter B and Sun, Heather H and Yeda, Kelly T and Doench, John G and Reichert, Elaine and Kung, Andrew L and Rodig, Scott J and Young, Richard A and Shipp, Margaret A and Bradner, James E},
date = {2013-12},
journaltitle = {Cancer Cell},
volume = {24},
number = {6},
pages = {777--790}
}
@article{chapuyGenomicAnalysesPMBL2019,
title = {Genomic Analyses of {{PMBL}} Reveal New Drivers and Mechanisms of Sensitivity to {{PD-1}} Blockade},
author = {Chapuy, Bjoern and Stewart, Chip and Dunford, Andrew J. and Kim, Jaegil and Wienand, Kirsty and Kamburov, Atanas and Griffin, Gabriel K. and Chen, Pei-Hsuan and Lako, Ana and Redd, Robert A. and Cote, Claire M. and Ducar, Matthew D. and Thorner, Aaron R. and Rodig, Scott J. and Getz, Gad and Shipp, Margaret A.},
date = {2019-12-26},
journaltitle = {Blood},
shortjournal = {Blood},
volume = {134},
number = {26},
eprint = {31697821},
eprinttype = {pmid},
pages = {2369--2382},
issn = {1528-0020},
doi = {10.1182/blood.2019002067},
abstract = {Primary mediastinal large B-cell lymphomas (PMBLs) are aggressive tumors that typically present as large mediastinal masses in young women. PMBLs share clinical, transcriptional, and molecular features with classical Hodgkin lymphoma (cHL), including constitutive activation of nuclear factor κB (NF-κB), JAK/STAT signaling, and programmed cell death protein 1 (PD-1)-mediated immune evasion. The demonstrated efficacy of PD-1 blockade in relapsed/refractory PMBLs led to recent approval by the US Food and Drug Administration and underscored the importance of characterizing targetable genetic vulnerabilities in this disease. Here, we report a comprehensive analysis of recurrent genetic alterations -somatic mutations, somatic copy number alterations, and structural variants-in a cohort of 37 newly diagnosed PMBLs. We identified a median of 9 genetic drivers per PMBL, including known and newly identified components of the JAK/STAT and NF-κB signaling pathways and frequent B2M alterations that limit major histocompatibility complex class I expression, as in cHL. PMBL also exhibited frequent, newly identified driver mutations in ZNF217 and an additional epigenetic modifier, EZH2. The majority of these alterations were clonal, which supports their role as early drivers. In PMBL, we identified several previously uncharacterized molecular features that may increase sensitivity to PD-1 blockade, including high tumor mutational burden, microsatellite instability, and an apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC) mutational signature. The shared genetic features between PMBL and cHL provide a framework for analyzing the mechanism of action of PD-1 blockade in these related lymphoid malignancies.},
langid = {english},
pmcid = {PMC6933293},
keywords = {Adult,Antineoplastic Agents Immunological,Biomarkers Tumor,Cohort Studies,DNA Copy Number Variations,Female,Gene Expression Regulation Neoplastic,Genomics,Humans,Lymphoma Large B-Cell Diffuse,Male,Mediastinal Neoplasms,Mutation,Prognosis,Programmed Cell Death 1 Receptor,Trans-Activators}
}
@article{chapuyMolecularSubtypesDiffuse2018,
title = {Molecular Subtypes of Diffuse Large {{B}} Cell Lymphoma Are Associated with Distinct Pathogenic Mechanisms and Outcomes},
author = {Chapuy, Bjoern and Stewart, Chip and Dunford, Andrew J. and Kim, Jaegil and Kamburov, Atanas and Redd, Robert A. and Lawrence, Mike S. and Roemer, Margaretha G. M. and Li, Amy J. and Ziepert, Marita and Staiger, Annette M. and Wala, Jeremiah A. and Ducar, Matthew D. and Leshchiner, Ignaty and Rheinbay, Ester and Taylor-Weiner, Amaro and Coughlin, Caroline A. and Hess, Julian M. and Pedamallu, Chandra S. and Livitz, Dimitri and Rosebrock, Daniel and Rosenberg, Mara and Tracy, Adam A. and Horn, Heike and family=Hummelen, given=Paul, prefix=van, useprefix=true and Feldman, Andrew L. and Link, Brian K. and Novak, Anne J. and Cerhan, James R. and Habermann, Thomas M. and Siebert, Reiner and Rosenwald, Andreas and Thorner, Aaron R. and Meyerson, Matthew L. and Golub, Todd R. and Beroukhim, Rameen and Wulf, Gerald G. and Ott, German and Rodig, Scott J. and Monti, Stefano and Neuberg, Donna S. and Loeffler, Markus and Pfreundschuh, Michael and Trümper, Lorenz and Getz, Gad and Shipp, Margaret A.},
date = {2018-05},
journaltitle = {Nature Medicine},
shortjournal = {Nat Med},
volume = {24},
number = {5},
eprint = {29713087},
eprinttype = {pmid},
pages = {679--690},
issn = {1546-170X},
doi = {10.1038/s41591-018-0016-8},
abstract = {Diffuse large B cell lymphoma (DLBCL), the most common lymphoid malignancy in adults, is a clinically and genetically heterogeneous disease that is further classified into transcriptionally defined activated B cell (ABC) and germinal center B cell (GCB) subtypes. We carried out a comprehensive genetic analysis of 304 primary DLBCLs and identified low-frequency alterations, captured recurrent mutations, somatic copy number alterations, and structural variants, and defined coordinate signatures in patients with available outcome data. We integrated these genetic drivers using consensus clustering and identified five robust DLBCL subsets, including a previously unrecognized group of low-risk ABC-DLBCLs of extrafollicular/marginal zone origin; two distinct subsets of GCB-DLBCLs with different outcomes and targetable alterations; and an ABC/GCB-independent group with biallelic inactivation of TP53, CDKN2A loss, and associated genomic instability. The genetic features of the newly characterized subsets, their mutational signatures, and the temporal ordering of identified alterations provide new insights into DLBCL pathogenesis. The coordinate genetic signatures also predict outcome independent of the clinical International Prognostic Index and suggest new combination treatment strategies. More broadly, our results provide a roadmap for an actionable DLBCL classification.},
langid = {english},
pmcid = {PMC6613387},
keywords = {DNA Copy Number Variations,Gene Rearrangement,Genes Neoplasm,Genetic Heterogeneity,Humans,Lymphoma Large B-Cell Diffuse,Mutation,Mutation Rate,Treatment Outcome}
}
@article{cheahMantleCellLymphoma2016,
title = {Mantle {{Cell Lymphoma}}},
author = {Cheah, Chan Yoon and Seymour, John F. and Wang, Michael L.},
date = {2016-04-10},
journaltitle = {Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology},
shortjournal = {J. Clin. Oncol.},
volume = {34},
number = {11},
eprint = {26755518},
eprinttype = {pmid},
pages = {1256--1269},
issn = {1527-7755},
doi = {10.1200/JCO.2015.63.5904},
abstract = {Mantle cell lymphoma (MCL) is an uncommon subtype of non-Hodgkin lymphoma previously considered to have a poor prognosis. Large gains were made in the first decade of the new century when clinical trials established the importance of high-dose therapy and autologous stem-cell rescue and high-dose cytarabine in younger patients and the benefits of maintenance rituximab and bendamustine in older patients. In particular, greater depth of understanding of the molecular pathophysiology of MCL has resulted in an explosion of specifically targeted new efficacious agents. In particular, agents recently approved by the Food and Drug Administration include the proteasome inhibitor bortezomib, immunomodulator lenalidomide, and Bruton's tyrosine kinase inhibitor ibrutinib. We review recent advances in the understanding of MCL biology and outline our recommended approach to therapy, including choice of chemoimmunotherapy, the role of stem-cell transplantation, and mechanism-based targeted therapies, on the basis of a synthesis of the data from published clinical trials.},
langid = {english},
keywords = {Antineoplastic Agents,Antineoplastic Combined Chemotherapy Protocols,Bendamustine Hydrochloride,Bortezomib,Cytarabine,Drug Administration Schedule,Gene Expression Profiling,Gene Expression Regulation Neoplastic,Hematopoietic Stem Cell Transplantation,Humans,Induction Chemotherapy,Lenalidomide,Lymphoma Mantle-Cell,Maintenance Chemotherapy,Molecular Targeted Therapy,Neoplasm Staging,Prognosis,Pyrazoles,Pyrimidines,Risk Factors,Rituximab,Thalidomide,Transplantation Autologous}
}
@article{chenSYKdependentTonicBcell,
title = {{{SYK-dependent}} Tonic {{B-cell}} Receptor Signaling Is a Rational Treatment Target in Diffuse Large {{B-cell}} Lymphoma.},
author = {Chen, Linfeng and Monti, Stefano and Juszczynski, Przemyslaw and Daley, John and Chen, Wen and Witzig, Thomas E and Habermann, Thomas M and Kutok, Jeffery L and Shipp, Margaret A},
journaltitle = {Blood},
volume = {111},
number = {4},
pages = {2230--2237}
}
@article{cheungAcquiredTNFRSF14Mutations2010,
title = {Acquired {{TNFRSF14}} Mutations in Follicular Lymphoma Are Associated with Worse Prognosis},
author = {Cheung, K.-John J. and Johnson, Nathalie A. and Affleck, Joslynn G. and Severson, Tesa and Steidl, Christian and Ben-Neriah, Susana and Schein, Jacqueline and Morin, Ryan D. and Moore, Richard and Shah, Sohrab P. and Qian, Hong and Paul, Jessica E. and Telenius, Adele and Relander, Thomas and Lam, Wan and Savage, Kerry and Connors, Joseph M. and Brown, Carolyn and Marra, Marco A. and Gascoyne, Randy D. and Horsman, Douglas E.},
date = {2010-11-15},
journaltitle = {Cancer Research},
shortjournal = {Cancer Res},
volume = {70},
number = {22},
eprint = {20884631},
eprinttype = {pmid},
pages = {9166--9174},
issn = {1538-7445},
doi = {10.1158/0008-5472.CAN-10-2460},
abstract = {Clinical correlative studies have linked 1p36 deletions with worse prognosis in follicular lymphoma (FL). In this study, we sought to identify the critical gene(s) in this region that is responsible for conferring inferior prognosis. BAC array technology applied to 141 FL specimens detected a minimum region of deletion (MRD) of ∼97 kb within 1p36.32 in 20\% of these cases. Frequent single-nucleotide polymorphism-detected copy-neutral loss of heterozygosity was also found in this region. Analysis of promoter CpGs in the MRD did not reveal differential patterns of DNA methylation in samples that differed in 1p36 status. Exon sequencing of MRD genes identified somatic alterations in the TNFRSF14 gene in 3 of 11 selected cases with matching normal DNA. An expanded cohort consisting of 251 specimens identified 46 cases (18.3\%) with nonsynonymous mutations affecting TNFRSF14. Overall survival (OS) and disease-specific survival (DSS) were associated with the presence of TNFRSF14 mutation in patients whose overall treatment included rituximab. We further showed that inferior OS and DSS were most pronounced in patients whose lymphomas contained both TNFRSF14 mutations and 1p36 deletions after adjustment for the International Prognostic Index [hazard ratios of 3.65 (95\% confidence interval, 1.35-9.878, P=0.011) and 3.19 (95\% confidence interval, 1.06-9.57, P=0.039), respectively]. Our findings identify TNFRSF14 as a candidate gene associated with a subset of FL, based on frequent occurrence of acquired mutations and their correlation with inferior clinical outcomes.},
langid = {english},
keywords = {Antibodies Monoclonal Murine-Derived,Antineoplastic Combined Chemotherapy Protocols,Chromosome Deletion,Chromosomes Artificial Bacterial,Chromosomes Human Pair 1,Comparative Genomic Hybridization,CpG Islands,Disease-Free Survival,DNA Methylation,Female,Genetic Predisposition to Disease,Humans,In Situ Hybridization Fluorescence,Lymphoma Follicular,Male,Middle Aged,Multivariate Analysis,Mutation,Prognosis,Receptors Tumor Necrosis Factor Member 14,Rituximab}
}
@article{choiNewImmunostainAlgorithm2009,
title = {A {{New Immunostain Algorithm Classifies Diffuse Large B-Cell Lymphoma}} into {{Molecular Subtypes}} with {{High Accuracy}}},
author = {Choi, W W L and Weisenburger, D D and Greiner, T C and Piris, M A and Banham, A H and Delabie, J and Braziel, R M and Geng, H and Iqbal, J and Lenz, G and Vose, J M and Hans, C P and Fu, K and Smith, L M and Li, M and Liu, Z and Gascoyne, R D and Rosenwald, A and Ott, G and Rimsza, L M and Campo, E and Jaffe, E S and Jaye, D L and Staudt, L M and Chan, W C},
date = {2009-08},
journaltitle = {Clin Cancer Res},
volume = {15},
number = {17},
pages = {5494--5502}
}
@article{chongComprehensiveCharacterizationProgrammed2016,
title = {Comprehensive Characterization of Programmed Death Ligand Structural Rearrangements in {{B-cell}} Non-{{Hodgkin}} Lymphomas},
author = {Chong, Lauren C. and Twa, David D. W. and Mottok, Anja and Ben-Neriah, Susana and Woolcock, Bruce W. and Zhao, Yongjun and Savage, Kerry J. and Marra, Marco A. and Scott, David W. and Gascoyne, Randy D. and Morin, Ryan D. and Mungall, Andrew J. and Steidl, Christian},
date = {2016-09-01},
journaltitle = {Blood},
shortjournal = {Blood},
volume = {128},
number = {9},
eprint = {27268263},
eprinttype = {pmid},
pages = {1206--1213},
issn = {1528-0020},
doi = {10.1182/blood-2015-11-683003},
abstract = {Programmed death ligands (PDLs) are immune-regulatory molecules that are frequently affected by chromosomal alterations in B-cell lymphomas. Although PDL copy-number variations are well characterized, a detailed and comprehensive analysis of structural rearrangements (SRs) and associated phenotypic consequences is largely lacking. Here, we used oligonucleotide capture sequencing of 67 formalin-fixed paraffin-embedded tissues derived from primary B-cell lymphomas and 1 cell line to detect and characterize, at base-pair resolution, SRs of the PDL locus (9p24.1; harboring PDL1/CD274 and PDL2/PDCD1LG2). We describe 36 novel PDL SRs, including 17 intrachromosomal events (inversions, duplications, deletions) and 19 translocations involving BZRAP-AS1, CD44, GET4, IL4R, KIAA0226L, MID1, RCC1, PTPN1 and segments of the immunoglobulin loci. Moreover, analysis of the precise chromosomal breakpoints reveals 2 distinct cluster breakpoint regions (CBRs) within either CD274 (CBR1) or PDCD1LG2 (CBR2). To determine the phenotypic consequences of these SRs, we performed immunohistochemistry for CD274 and PDCD1LG2 on primary pretreatment biopsies and found that PDL SRs are significantly associated with PDL protein expression. Finally, stable ectopic expression of wild-type PDCD1LG2 and the PDCD1LG2-IGHV7-81 fusion showed, in coculture, significantly reduced T-cell activation. Taken together, our data demonstrate the complementary utility of fluorescence in situ hybridization and capture sequencing approaches and provide a classification scheme for PDL SRs with implications for future studies using PDL immune-checkpoint inhibitors in B-cell lymphomas.},
langid = {english},
keywords = {B7-H1 Antigen,Cell Line Tumor,Chromosome Aberrations,Chromosomes Human,Female,Genetic Loci,Humans,Lymphoma B-Cell,Male,Programmed Cell Death 1 Ligand 2 Protein}
}
@article{chongHighresolutionArchitecturePartner2018,
title = {High-Resolution Architecture and Partner Genes of {{MYC}} Rearrangements in Lymphoma with {{DLBCL}} Morphology},
author = {Chong, Lauren C. and Ben-Neriah, Susana and Slack, Graham W. and Freeman, Ciara and Ennishi, Daisuke and Mottok, Anja and Collinge, Brett and Abrisqueta, Pau and Farinha, Pedro and Boyle, Merrill and Meissner, Barbara and Kridel, Robert and Gerrie, Alina S. and Villa, Diego and Savage, Kerry J. and Sehn, Laurie H. and Siebert, Reiner and Morin, Ryan D. and Gascoyne, Randy D. and Marra, Marco A. and Connors, Joseph M. and Mungall, Andrew J. and Steidl, Christian and Scott, David W.},
date = {2018-10-23},
journaltitle = {Blood Advances},
shortjournal = {Blood Adv},
volume = {2},
number = {20},
eprint = {30348671},
eprinttype = {pmid},
pages = {2755--2765},
issn = {2473-9537},
doi = {10.1182/bloodadvances.2018023572},
abstract = {Genomic rearrangements in the MYC locus occur in ∼12\% of lymphomas with diffuse large B-cell lymphoma (DLBCL) morphology and are associated with inferior outcome. Previous studies exploring MYC rearrangements have primarily used fluorescence in situ hybridization (FISH) assays to characterize break-apart status but have rarely examined breakpoint location, and in some cases have not examined partner identity. We performed targeted sequencing of MYC, BCL2, BCL6, and the immunoglobulin (IG) loci in 112 tumors with DLBCL morphology harboring MYC rearrangement. We characterized the location of the MYC rearrangement at base pair resolution and identified the partner in 88 cases. We observed a cluster of breakpoints upstream of the MYC coding region and in intron 1 (the "genic cluster"). Genic cluster rearrangements were enriched for translocations involving IGH (80\%), whereas nongenic rearrangements occurred mostly downstream of the MYC gene with a variety of partners, including IGL and IGK Other recurrent partners included BCL6, ZCCHC7, and RFTN1, which has not previously been described as a MYC partner. We compared 2 commercially available FISH break-apart assays for the MYC locus and observed discordant results in 32\% of cases examined, including some with MYC-IGL and MYC-IGK rearrangements. In cases of high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangement (HGBL-DH), so-called "double-hit" lymphomas, the majority of MYC rearrangements had non-IG partners (65\%), with breakpoints outside the genic cluster (72\%). In patients with de novo HGBL-DH of DLBCL morphology, MYC-IG rearrangements showed a trend toward inferior time to progression and overall survival compared with MYC-non-IG rearrangements. Our data reveal clinically relevant architecture of MYC rearrangements in lymphomas with DLBCL morphology.},
langid = {english},
pmcid = {PMC6199666}
}
@article{choPolyBindingProtein2013,
title = {Poly ({{C}})-{{Binding Protein}} 1 {{Regulates}} P63 {{Expression}} through {{mRNA Stability}}},
author = {Cho, Seong-Jun and Jung, Yong-Sam and Chen, Xinbin},
date = {2013-08-07},
journaltitle = {PLOS ONE},
shortjournal = {PLOS ONE},
volume = {8},
number = {8},
pages = {e71724},
publisher = {Public Library of Science},
issn = {1932-6203},
doi = {10.1371/journal.pone.0071724},
url = {https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0071724},
urldate = {2022-09-28},
abstract = {p63, a transcription factor and p53 family protein, plays a crucial role in tumor suppression and development of various epithelial tissues. While p63 expression is controlled mostly by post-translational modifications, recent studies indicate that transcriptional and posttranscriptional regulations are essential for proper p63 expression. Here, we investigated the regulation of p63 expression by poly (C)-binding protein 1 (PCBP1, also known as hnRNP-E1 and αCP1). We found that knockdown of PCBP1 decreases the level of p63 transcript and protein. We also found that PCBP1 regulates the stability of p63 mRNA via binding to p63 3’UTR. Additionally, we found that a CU-rich element (CUE) in p63 3′UTR is bound by and responsive to PCBP1. Together, we conclude that PCBP1 regulates p63 expression via mRNA stability.},
langid = {english},
keywords = {Gene expression,Lentivirus,Luciferase,Messenger RNA,Polymerase chain reaction,Protein translation,Reverse transcriptase-polymerase chain reaction,RNA probes}
}
@article{choPromoterLncRNAGene2018,
title = {Promoter of {{lncRNA Gene PVT1 Is}} a {{Tumor-Suppressor DNA Boundary Element}}},
author = {Cho, Seung Woo and Xu, Jin and Sun, Ruping and Mumbach, Maxwell R. and Carter, Ava C. and Chen, Y. Grace and Yost, Kathryn E. and Kim, Jeewon and He, Jing and Nevins, Stephanie A. and Chin, Suet-Feung and Caldas, Carlos and Liu, S. John and Horlbeck, Max A. and Lim, Daniel A. and Weissman, Jonathan S. and Curtis, Christina and Chang, Howard Y.},
date = {2018-05-31},
journaltitle = {Cell},
shortjournal = {Cell},
volume = {173},
number = {6},
eprint = {29731168},
eprinttype = {pmid},
pages = {1398-1412.e22},
issn = {1097-4172},
doi = {10.1016/j.cell.2018.03.068},
abstract = {Noncoding mutations in cancer genomes are frequent~but challenging to interpret. PVT1 encodes an oncogenic lncRNA, but recurrent translocations and deletions in human cancers suggest alternative mechanisms. Here, we show that the PVT1 promoter has a tumor-suppressor function that is independent of PVT1 lncRNA. CRISPR interference of PVT1 promoter enhances breast cancer cell competition and growth in~vivo. The promoters of the PVT1 and the MYC oncogenes, located 55 kb apart on chromosome 8q24, compete for engagement with four intragenic enhancers in the PVT1 locus, thereby allowing the PVT1 promoter to regulate pause release of MYC transcription. PVT1 undergoes developmentally regulated monoallelic expression, and the PVT1 promoter inhibits MYC expression only from the same chromosome via promoter competition. Cancer genome sequencing identifies recurrent mutations encompassing the human PVT1 promoter, and genome editing verified that PVT1 promoter mutation promotes cancer cell growth. These results highlight regulatory sequences of lncRNA genes as potential disease-associated DNA elements.},
langid = {english},
pmcid = {PMC5984165},
keywords = {Animals,Breast Neoplasms,Carcinogenesis,Cell Line Tumor,Cell Proliferation,Cell Transformation Neoplastic,Chromatin,CRISPR-Cas Systems,CRISPRi,DNA Neoplasm,enhancer,Enhancer Elements Genetic,Female,Gene Expression Profiling,Gene Expression Regulation Neoplastic,Genes myc,Humans,lncRNA,Mice,Mice Inbred NOD,Mutation,MYC,Neoplasm Transplantation,promoter,Promoter Regions Genetic,PVT1,RNA Long Noncoding,topological domains,Transcription Genetic,transcriptional regulation,tumor suppressor}
}
@article{choudhurySplicingActivatorDAZAP12014,
title = {The Splicing Activator {{DAZAP1}} Integrates Splicing Control into {{MEK}}/{{Erk-regulated}} Cell Proliferation and Migration},
author = {Choudhury, Rajarshi and Roy, Sreerupa Ghose and Tsai, Yihsuan S. and Tripathy, Ashutosh and Graves, Lee M. and Wang, Zefeng},
date = {2014-01-23},
journaltitle = {Nature Communications},
volume = {5},
pages = {3078},
issn = {2041-1723},
doi = {10.1038/ncomms4078},
url = {https://www.nature.com/articles/ncomms4078},
urldate = {2018-08-23},
abstract = {Alternative splicing of pre-messenger RNA (mRNA) is a critical stage of gene regulation in response to environmental stimuli. Here we show that DAZAP1, an RNA-binding protein involved in mammalian development and spermatogenesis, promotes inclusion of weak exons through specific recognition of diverse cis-elements. The carboxy-terminal proline-rich domain of DAZAP1 interacts with and neutralizes general splicing inhibitors, and is sufficient to activate splicing when recruited to pre-mRNA. This domain is phosphorylated by the MEK/Erk (extracellular signal-regulated protein kinase) pathway and this modification is essential for the splicing regulatory activity and the nuclear/cytoplasmic translocation of DAZAP1. Using mRNA-seq, we identify endogenous splicing events regulated by DAZAP1, many of which are involved in maintaining cell growth. Knockdown or over-expression of DAZAP1 causes a cell proliferation defect. Taken together, these studies reveal a molecular mechanism that integrates splicing control into MEK/Erk-regulated cell proliferation.},
langid = {english}
}
@article{cifuentesZC3H12AMCPIP1Molecular2010,
title = {{{ZC3H12A}} ({{MCPIP1}}): {{Molecular}} Characteristics and Clinical Implications},
author = {Cifuentes, Ricardo A and Cruz-Tapias, Paola and Rojas-Villarraga, Adriana and Anaya, Juan-Manuel},
date = {2010-12},
journaltitle = {Clinica Chimica Acta},
volume = {411},
number = {23-24},
pages = {1862--1868}
}
@article{compagnoMutationsMultipleGenes2009,
title = {Mutations of Multiple Genes Cause Deregulation of {{NF-kappaB}} in Diffuse Large {{B-cell}} Lymphoma},
author = {Compagno, Mara and Lim, Wei Keat and Grunn, Adina and Nandula, Subhadra V. and Brahmachary, Manisha and Shen, Qiong and Bertoni, Francesco and Ponzoni, Maurilio and Scandurra, Marta and Califano, Andrea and Bhagat, Govind and Chadburn, Amy and Dalla-Favera, Riccardo and Pasqualucci, Laura},
date = {2009-06-04},
journaltitle = {Nature},
shortjournal = {Nature},
volume = {459},
number = {7247},
eprint = {19412164},
eprinttype = {pmid},
pages = {717--721},
issn = {1476-4687},
doi = {10.1038/nature07968},
abstract = {Diffuse large B-cell lymphoma (DLBCL), the most common form of lymphoma in adulthood, comprises multiple biologically and clinically distinct subtypes including germinal centre B-cell-like (GCB) and activated B-cell-like (ABC) DLBCL. Gene expression profile studies have shown that its most aggressive subtype, ABC-DLBCL, is associated with constitutive activation of the NF-kappaB transcription complex. However, except for a small fraction of cases, it remains unclear whether NF-kappaB activation in these tumours represents an intrinsic program of the tumour cell of origin or a pathogenetic event. Here we show that {$>$}50\% of ABC-DLBCL and a smaller fraction of GCB-DLBCL carry somatic mutations in multiple genes, including negative (TNFAIP3, also called A20) and positive (CARD11, TRAF2, TRAF5, MAP3K7 (TAK1) and TNFRSF11A (RANK)) regulators of NF-kappaB. Of these, the A20 gene, which encodes a ubiquitin-modifying enzyme involved in termination of NF-kappaB responses, is most commonly affected, with approximately 30\% of patients displaying biallelic inactivation by mutations and/or deletions. When reintroduced in cell lines carrying biallelic inactivation of the gene, A20 induced apoptosis and cell growth arrest, indicating a tumour suppressor role. Less frequently, missense mutations of TRAF2 and CARD11 produce molecules with significantly enhanced ability to activate NF-kappaB. Thus, our results demonstrate that NF-kappaB activation in DLBCL is caused by genetic lesions affecting multiple genes, the loss or activation of which may promote lymphomagenesis by leading to abnormally prolonged NF-kappaB responses.},
langid = {english},
pmcid = {PMC2973325},
keywords = {Apoptosis,Cell Line Tumor,DNA-Binding Proteins,Gene Expression Regulation Neoplastic,Genes,Humans,Intracellular Signaling Peptides and Proteins,Lymphoma Large B-Cell Diffuse,Mutation,NF-kappa B,Nuclear Proteins,Tumor Necrosis Factor alpha-Induced Protein 3}
}
@article{copie-bergmanMYCIGRearrangementsAre2015,
title = {{{MYC-IG}} Rearrangements Are Negative Predictors of Survival in {{DLBCL}} Patients Treated with Immunochemotherapy: A {{GELA}}/{{LYSA}} Study},
shorttitle = {{{MYC-IG}} Rearrangements Are Negative Predictors of Survival in {{DLBCL}} Patients Treated with Immunochemotherapy},
author = {Copie-Bergman, Christiane and Cuillière-Dartigues, Peggy and Baia, Maryse and Briere, Josette and Delarue, Richard and Canioni, Danielle and Salles, Gilles and Parrens, Marie and Belhadj, Karim and Fabiani, Bettina and Recher, Christian and Petrella, Tony and Ketterer, Nicolas and Peyrade, Frederic and Haioun, Corinne and Nagel, Inga and Siebert, Reiner and Jardin, Fabrice and Leroy, Karen and Jais, Jean-Philippe and Tilly, Herve and Molina, Thierry Jo and Gaulard, Philippe},
date = {2015-11-26},
journaltitle = {Blood},
volume = {126},
number = {22},
eprint = {26373676},
eprinttype = {pmid},
pages = {2466--2474},
issn = {0006-4971, 1528-0020},
doi = {10.1182/blood-2015-05-647602},
url = {http://www.bloodjournal.org/content/126/22/2466},
urldate = {2019-07-15},
abstract = {Diffuse large B-cell lymphoma (DLBCL) with MYC rearrangement (MYC-R) carries an unfavorable outcome. We explored the prognostic value of the MYC translocation partner gene in a series of MYC-R de novo DLBCL patients enrolled in first-line prospective clinical trials (Groupe d’Etudes des Lymphomes de l’Adulte/Lymphoma Study Association) and treated with rituximab-anthracycline–based chemotherapy. A total of 774 DLBCL cases characterized for cell of origin by the Hans classifier were analyzed using fluorescence in situ hybridization with BCL2, BCL6, MYC, immunoglobulin (IG)K, and IGL break-apart and IGH/MYC, IGK/MYC, and IGL/MYC fusion probes. MYC-R was observed in 51/574 (8.9\%) evaluable DLBCL cases. MYC-R cases were predominantly of the germinal center B-cell–like subtype 37/51 (74\%) with no distinctive morphologic and phenotypic features. Nineteen cases were MYC single-hit and 32 cases were MYC double-hit (MYC plus BCL2 and/or BCL6) DLBCL. MYC translocation partner was an IG gene in 24 cases (MYC-IG) and a non-IG gene (MYC-non-IG) in 26 of 50 evaluable cases. Noteworthy, MYC-IG patients had shorter overall survival (OS) (P = .0002) compared with MYC-negative patients, whereas no survival difference was observed between MYC-non-IG and MYC-negative patients. In multivariate analyses, MYC-IG predicted poor progression-free survival (P = .0051) and OS (P = .0006) independently from the International Prognostic Index and the Hans classifier. In conclusion, we show in this prospective randomized trial that the adverse prognostic impact of MYC-R is correlated to the MYC-IG translocation partner gene in DLBCL patients treated with immunochemotherapy. These results may have an important impact on the clinical management of DLBCL patients with MYC-R who should be routinely characterized according to MYC partner gene. These trials are individually registered at www.clinicaltrials.gov as \#NCT00144807, \#NCT01087424, \#NCT00169143, \#NCT00144755, \#NCT00140660, \#NCT00140595, and \#NCT00135499.},
langid = {english}
}
@article{courtsRecurrentInactivationPRDM12008,
title = {Recurrent Inactivation of the {{PRDM1}} Gene in Primary Central Nervous System Lymphoma},
author = {Courts, Cornelius and Montesinos-Rongen, Manuel and Brunn, Anna and Bug, Stefanie and Siemer, Dörte and Hans, Volkmar and Blümcke, Ingmar and Klapper, Wolfram and Schaller, Carlo and Wiestler, Otmar D. and Küppers, Ralf and Siebert, Reiner and Deckert, Martina},
date = {2008-07},
journaltitle = {Journal of Neuropathology and Experimental Neurology},
shortjournal = {J Neuropathol Exp Neurol},
volume = {67},
number = {7},
eprint = {18596541},
eprinttype = {pmid},
pages = {720--727},
issn = {0022-3069},
doi = {10.1097/NEN.0b013e31817dd02d},
abstract = {Primary lymphomas of the CNS (PCNSLs) show molecular features of the late germinal center exit B-cell phenotype and are impaired in their terminal differentiation as indicated by a lack of immunoglobulin class switching. Because the positive regulatory domain I protein with ZNF domain (PRDM1/BLIMP1) is a master regulator of terminal B-cell differentiation into plasma cells, we investigated a series of 21 PCNSLs for the presence of mutations in the PRDM1 gene and alterations in the expression pattern of the PRDM1 protein. Direct sequencing of all coding exons of the PRDM1 gene identified deleterious mutations associated with abrogation of PRDM1 protein expression in 4 of 21 (19\%) PCNSLs. Thus, similar to systemic diffuse large B-cell lymphomas, PRDM1 may be a tumor suppressor in some PCNSL and contribute to lymphomagenesis by impairing terminal differentiation.},
langid = {english},
keywords = {Adult,Aged,Aged 80 and over,Central Nervous System Neoplasms,DNA Mutational Analysis,Female,Gene Expression Regulation Neoplastic,Humans,Lymphoma B-Cell,Male,Middle Aged,Positive Regulatory Domain I-Binding Factor 1,Recurrence,Repressor Proteins,Sequence Deletion}
}
@article{crumpRandomizedComparisonGemcitabine2014,
title = {Randomized Comparison of Gemcitabine, Dexamethasone, and Cisplatin versus Dexamethasone, Cytarabine, and Cisplatin Chemotherapy before Autologous Stem-Cell Transplantation for Relapsed and Refractory Aggressive Lymphomas: {{NCIC-CTG LY}}.12},
shorttitle = {Randomized Comparison of Gemcitabine, Dexamethasone, and Cisplatin versus Dexamethasone, Cytarabine, and Cisplatin Chemotherapy before Autologous Stem-Cell Transplantation for Relapsed and Refractory Aggressive Lymphomas},
author = {Crump, Michael and Kuruvilla, John and Couban, Stephen and MacDonald, David A. and Kukreti, Vishal and Kouroukis, C. Tom and Rubinger, Morel and Buckstein, Rena and Imrie, Kevin R. and Federico, Massimo and Di Renzo, Nicola and Howson-Jan, Kang and Baetz, Tara and Kaizer, Leonard and Voralia, Michael and Olney, Harold J. and Turner, A. Robert and Sussman, Jonathan and Hay, Annette E. and Djurfeldt, Marina S. and Meyer, Ralph M. and Chen, Bingshu E. and Shepherd, Lois E.},
date = {2014-11-01},
journaltitle = {Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology},
shortjournal = {J Clin Oncol},
volume = {32},
number = {31},
eprint = {25267740},
eprinttype = {pmid},
pages = {3490--3496},
issn = {1527-7755},
doi = {10.1200/JCO.2013.53.9593},
abstract = {PURPOSE: For patients with relapsed or refractory aggressive lymphoma, we hypothesized that gemcitabine-based therapy before autologous stem-cell transplantation (ASCT) is as effective as and less toxic than standard treatment. PATIENTS AND METHODS: We randomly assigned 619 patients with relapsed/refractory aggressive lymphoma to treatment with gemcitabine, dexamethasone, and cisplatin (GDP) or to dexamethasone, cytarabine, and cisplatin (DHAP). Patients with B-cell lymphoma also received rituximab. Responding patients proceeded to stem-cell collection and ASCT. Coprimary end points were response rate after two treatment cycles and transplantation rate. The noninferiority margin for the response rate to GDP relative to DHAP was set at 10\%. Secondary end points included event-free and overall survival, treatment toxicity, and quality of life. RESULTS: For the intention-to-treat population, the response rate with GDP was 45.2\%; with DHAP the response rate was 44.0\% (95\% CI for difference, -9.0\% to 6.7\%), meeting protocol-defined criteria for noninferiority of GDP (P = .005). Similar results were obtained in a per-protocol analysis. The transplantation rates were 52.1\% with GDP and 49.3\% with DHAP (P = .44). At a median follow-up of 53 months, no differences were detected in event-free survival (HR, 0.99; stratified log-rank P = .95) or overall survival (HR, 1.03; P = .78) between GDP and DHAP. Treatment with GDP was associated with less toxicity (P {$<$} .001) and need for hospitalization (P {$<$} .001), and preserved quality of life (P = .04). CONCLUSION: For patients with relapsed or refractory aggressive lymphoma, in comparison with DHAP, treatment with GDP is associated with a noninferior response rate, similar transplantation rate, event-free survival, and overall survival, less toxicity and hospitalization, and superior quality of life.},
langid = {english},
keywords = {Adolescent,Adult,Aged,Antineoplastic Combined Chemotherapy Protocols,Cisplatin,Cytarabine,Deoxycytidine,Dexamethasone,Female,Hematopoietic Stem Cell Transplantation,Humans,Lymphoma,Male,Middle Aged,Quality of Life,Survival Rate,Transplantation Autologous,Treatment Outcome}
}
@article{curryPrognosticImpactCREL2009,
title = {Prognostic Impact of {{C-REL}} Expression in Diffuse Large {{B-cell}} Lymphoma},
author = {Curry, Choladda and Ewton, April and Olsen, Randall and Logan, Brent and Preti, Hector and Liu, Yao-Chang and Perkins, Sherrie and Chang, Chung-Che},
date = {2009},
journaltitle = {Journal of Hematopathology},
volume = {2},
number = {1},
pages = {20--26}
}
@article{daiCharacterizationMouseDazap12001,
title = {Characterization of the Mouse {{Dazap1}} Gene Encoding an {{RNA-binding}} Protein That Interacts with Infertility Factors {{DAZ}} and {{DAZL}}},
author = {Dai, Tiane and Vera, Yanira and Salido, Eduardo C and Yen, Pauline H},
date = {2001-09-26},
journaltitle = {BMC Genomics},
shortjournal = {BMC Genomics},
volume = {2},
eprint = {11604102},
eprinttype = {pmid},
pages = {6},
issn = {1471-2164},
doi = {10.1186/1471-2164-2-6},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC57980/},
urldate = {2018-08-23},
abstract = {Background DAZAP1 (DAZ Associated Protein 1) was originally identified by a yeast two-hybrid system through its interaction with a putative male infertility factor, DAZ (Deleted in Azoospermia). In vitro, DAZAP1 interacts with both the Y chromosome-encoded DAZ and an autosome-encoded DAZ-like protein, DAZL. DAZAP1 contains two RNA-binding domains (RBDs) and a proline-rich C-terminal portion, and is expressed most abundantly in the testis. To understand the biological function of DAZAP1 and the significance of its interaction with DAZ and DAZL, we isolated and characterized the mouse Dazap1 gene, and studied its expression and the subcellular localization of its protein product. Results The human and mouse genes have similar genomic structures and map to syntenic chromosomal regions. The mouse and human DAZAP1 proteins share 98\% identity and their sequences are highly similar to the Xenopus orthologue Prrp, especially in the RBDs. Dazap1 is expressed throughout testis development. Western blot detects a single 45 kD DAZAP1 protein that is most abundant in the testis. Although a majority of DAZAP1 is present in the cytoplasmic fraction, they are not associated with polyribosomes. Conclusions DAZAP1 is evolutionarily highly conserved. Its predominant expression in testes suggests a role in spermatogenesis. Its subcellular localization indicates that it is not directly involved in mRNA translation.},
pmcid = {PMC57980}
}
@article{daiGenomicLandscapePrimary2015,
title = {Genomic {{Landscape}} of {{Primary Mediastinal B-Cell Lymphoma Cell Lines}}},
author = {Dai, Haiping and Ehrentraut, Stefan and Nagel, Stefan and Eberth, Sonja and Pommerenke, Claudia and Dirks, Wilhelm G. and Geffers, Robert and Kalavalapalli, Srilaxmi and Kaufmann, Maren and Meyer, Corrina and Faehnrich, Silke and Chen, Suning and Drexler, Hans G. and MacLeod, Roderick A. F.},
date = {2015},
journaltitle = {PloS One},
shortjournal = {PLoS One},
volume = {10},
number = {11},
eprint = {26599546},
eprinttype = {pmid},
pages = {e0139663},
issn = {1932-6203},
doi = {10.1371/journal.pone.0139663},
abstract = {Primary mediastinal B-Cell lymphoma (PMBL) is a recently defined entity comprising \textasciitilde 2-10\% non-Hodgkin lymphomas (NHL). Unlike most NHL subtypes, PMBL lacks recurrent gene rearrangements to serve as biomarkers or betray target genes. While druggable, late chemotherapeutic complications warrant the search for new targets and models. Well characterized tumor cell lines provide unlimited material to serve as preclinical resources for verifiable analyses directed at the discovery of new biomarkers and pathological targets using high throughput microarray technologies. The same cells may then be used to seek intelligent therapies directed at clinically validated targets. Four cell lines have emerged as potential PMBL models: FARAGE, KARPAS-1106P, MEDB-1 and U-2940. Transcriptionally, PMBL cell lines cluster near c(lassical)-HL and B-NHL examples showing they are related but separate entities. Here we document genomic alterations therein, by cytogenetics and high density oligonucleotide/SNP microarrays and parse their impact by integrated global expression profiling. PMBL cell lines were distinguished by moderate chromosome rearrangement levels undercutting cHL, while lacking oncogene translocations seen in B-NHL. In total 61 deletions were shared by two or more cell lines, together with 12 amplifications (≥4x) and 72 homozygous regions. Integrated genomic and transcriptional profiling showed deletions to be the most important class of chromosome rearrangement. Lesions were mapped to several loci associated with PMBL, e.g. 2p15 (REL/COMMD1), 9p24 (JAK2, CD274), 16p13 (SOCS1, LITAF, CIITA); plus new or tenuously associated loci: 2p16 (MSH6), 6q23 (TNFAIP3), 9p22 (CDKN2A/B), 20p12 (PTPN1). Discrete homozygous regions sometimes substituted focal deletions accompanied by gene silencing implying a role for epigenetic or mutational inactivation. Genomic amplifications increasing gene expression or gene-activating rearrangements were respectively rare or absent. Our findings highlight biallelic deletions as a major class of chromosomal lesion in PMBL cell lines, while endorsing the latter as preclinical models for hunting and testing new biomarkers and actionable targets.},
langid = {english},
pmcid = {PMC4657880},
keywords = {Aged,Cell Line Tumor,Cluster Analysis,Comparative Genomic Hybridization,Cytogenetic Analysis,DNA Copy Number Variations,Female,Gene Expression Profiling,Gene Expression Regulation Neoplastic,Genetic Loci,Genome Human,Humans,In Situ Hybridization Fluorescence,Loss of Heterozygosity,Lymphoma B-Cell,Mediastinal Neoplasms,Polymorphism Single Nucleotide,Principal Component Analysis,Spectral Karyotyping,Transcription Genetic}
}
@article{daviesComparisonMHGDZsig2023,
title = {Comparison of {{MHG}} and {{DZsig}} Reveals Shared Biology and a Core Overlap Group with Inferior Prognosis in {{DLBCL}}},
author = {Davies, John R. and Hilton, Laura K. and Jiang, Aixiang and Barrans, Sharon and Burton, Catherine and Johnson, Peter W. M. and Davies, Andrew J. and Du, Ming-Qing and Tooze, Reuben and Cucco, Francesco and Care, Matthew A. and Morin, Ryan D. and Steidl, Christian and Sha, Chulin and Westhead, David R. and Scott, David W.},
date = {2023-10-24},
journaltitle = {Blood Advances},
shortjournal = {Blood Advances},
volume = {7},
number = {20},
pages = {6156--6162},
issn = {2473-9529},
doi = {10.1182/bloodadvances.2023010673},
url = {https://doi.org/10.1182/bloodadvances.2023010673},
urldate = {2023-10-17},
abstract = {TO THE EDITOR:Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease identified by morphology, immunophenotype, and a typically aggressive clinical course.1 DLBCL has long been stratified based on gene expression profiling (GEP) into activated B-cell–like (ABC) and germinal center B-cell–like (GCB) cell-of-origin (COO) subtypes.2 Recently, several studies stratified DLBCL into genetic subgroups based on the co-occurrence of mutational features with strong associations with COO.3-6 Previously, our 2 groups independently reported gene expression signatures associated with dark-zone–like biology in DLBCL. The molecular high-grade signature (MHG) identifies DLBCLs expressing a Burkitt lymphoma (BL)-like GEP signature,7 whereas the double-hit signature (since renamed dark-zone signature [DZsig]8) identifies DLBCLs with a GEP signature like high-grade B-cell lymphoma with MYC and BCL2 rearrangement (HGBCL-DH-BCL2) (whether the tumors harbor MYC and BCL2 rearrangements or not).9,10 Remarkably, despite the small overlap in the genes that comprise each signature, both classifiers identified a subset of DLBCL tumors enriched for certain genetic aberrations, including concomitant MYC and BCL2 rearrangements.7,9}
}
@article{davisChronicActiveBcellreceptor2010,
title = {Chronic Active {{B-cell-receptor}} Signalling in Diffuse Large {{B-cell}} Lymphoma},
author = {Davis, R Eric and Ngo, Vu N and Lenz, Georg and Tolar, Pavel and Young, Ryan M and Romesser, Paul B and Kohlhammer, Holger and Lamy, Laurence and Zhao, Hong and Yang, Yandan and Xu, Weihong and Shaffer, Arthur L and Wright, George and Xiao, Wenming and Powell, John and Jiang, Jian-Kang and Thomas, Craig J and Rosenwald, Andreas and Ott, German and Müller-Hermelink, Hans-Konrad and Gascoyne, Randy D and Connors, Joseph M and Johnson, Nathalie A and Rimsza, Lisa M and Campo, Elias and Jaffe, Elaine S and Wilson, Wyndham H and Delabie, Jan and Smeland, Erlend B and Fisher, Richard I and Braziel, Rita M and Tubbs, Raymond R and Cook, J R and Weisenburger, Dennis D and Chan, Wing C and Pierce, Susan K and Staudt, Louis M},
date = {2010-01},
journaltitle = {Nature},
volume = {463},
number = {7277},
pages = {88--92},
pmcid = {PMC2845535}
}
@article{davisConstitutiveNuclearFactor2001,
title = {Constitutive Nuclear Factor {{kappaB}} Activity Is Required for Survival of Activated {{B}} Cell-like Diffuse Large {{B}} Cell Lymphoma Cells},
author = {Davis, R and Brown, K and Siebenlist, U and Staudt, L},
date = {2001},
journaltitle = {J Exp Med},
volume = {194},
number = {12},
pages = {1861--1874}
}
@article{dierlammGainChromosomeRegion2008,
title = {Gain of Chromosome Region 18q21 Including the {{MALT1}} Gene Is Associated with the Activated {{B-cell-like}} Gene Expression Subtype and Increased {{BCL2}} Gene Dosage and Protein Expression in Diffuse Large {{B-cell}} Lymphoma},
author = {Dierlamm, Judith and Murga Penas, Eva M and Bentink, Stefan and Wessendorf, Swen and Berger, Hilmar and Hummel, Michael and Klapper, Wolfram and Lenze, Dido and Rosenwald, Andreas and Haralambieva, Eugenia and Ott, German and Cogliatti, Sergio B and Möller, Peter and Schwaenen, Carsten and Stein, Harald and Löffler, Markus and Spang, Rainer and Trümper, Lorenz and Siebert, Reiner and Lymphomas, Deutsche Krebshilfe Network Project Molecular Mechanisms in Malignant},
date = {2008-05},
journaltitle = {Haematologica},
volume = {93},
number = {5},
pages = {688--696}
}
@article{dingConstitutivelyActivatedSTAT32008,
title = {Constitutively Activated {{STAT3}} Promotes Cell Proliferation and Survival in the Activated {{B-cell}} Subtype of Diffuse Large {{B-cell}} Lymphomas.},
author = {Ding, B Belinda and Yu, J Jessica and Yu, Raymond Y-L and Mendez, Lourdes M and Shaknovich, Rita and Zhang, Yonghui and Cattoretti, Giorgio and Ye, B Hilda},
date = {2008-02},
journaltitle = {Blood},
volume = {111},
number = {3},
pages = {1515--1523}
}
@article{drevalGeneticSubdivisionsFollicular2023,
title = {Genetic Subdivisions of Follicular Lymphoma Defined by Distinct Coding and Noncoding Mutation Patterns},
author = {Dreval, Kostiantyn and Hilton, Laura K. and Cruz, Manuela and Shaalan, Haya and Ben-Neriah, Susana and Boyle, Merrill and Collinge, Brett and Coyle, Krysta M. and Duns, Gerben and Farinha, Pedro and Grande, Bruno M. and Meissner, Barbara and Pararajalingam, Prasath and Rushton, Christopher K. and Slack, Graham W. and Wong, Jasper and Mungall, Andrew J. and Marra, Marco A. and Connors, Joseph M. and Steidl, Christian and Scott, David W. and Morin, Ryan D.},
date = {2023-08-10},
journaltitle = {Blood},
shortjournal = {Blood},
volume = {142},
number = {6},
eprint = {37084389},
eprinttype = {pmid},
pages = {561--573},
issn = {1528-0020},
doi = {10.1182/blood.2022018719},
abstract = {Follicular lymphoma (FL) accounts for ∼20\% of all new lymphoma cases. Increases in cytological grade are a feature of the clinical progression of this malignancy, and eventual histologic transformation (HT) to the aggressive diffuse large B-cell lymphoma (DLBCL) occurs in up to 15\% of patients. Clinical or genetic features to predict the risk and timing of HT have not been described comprehensively. In this study, we analyzed whole-genome sequencing data from 423 patients to compare the protein coding and noncoding mutation landscapes of untransformed FL, transformed FL, and de novo DLBCL. This revealed 2 genetically distinct subgroups of FL, which we have named DLBCL-like (dFL) and constrained FL (cFL). Each subgroup has distinguishing mutational patterns, aberrant somatic hypermutation rates, and biological and clinical characteristics. We implemented a machine learning-derived classification approach to stratify patients with FL into cFL and dFL subgroups based on their genomic features. Using separate validation cohorts, we demonstrate that cFL status, whether assigned with this full classifier or a single-gene approximation, is associated with a reduced rate of HT. This implies distinct biological features of cFL that constrain its evolution, and we highlight the potential for this classification to predict HT from genetic features present at diagnosis.},
langid = {english},
pmcid = {PMC10644066},
keywords = {Humans,Lymphoma Follicular,Lymphoma Large B-Cell Diffuse,Morinlab,Mutation}
}
@article{drevalMinimumInformationReporting2022,
title = {Minimum {{Information}} for {{Reporting}} a {{Genomics Experiment}}},
author = {Dreval, Kostiantyn and Boutros, Paul C. and Morin, Ryan D.},
date = {2022-10-11},
journaltitle = {Blood},
shortjournal = {Blood},
eprint = {36219881},
eprinttype = {pmid},
pages = {blood.2022016095},
issn = {1528-0020},
doi = {10.1182/blood.2022016095},
abstract = {Exome and genome sequencing has facilitated the identification of hundreds of genes and other regions that are recurrently mutated in hematologic neoplasms. The datasets from these studies theoretically provide opportunities. Quality differences between datasets can confound secondary analyses. We explore the consequences of these on the conclusions from some recent studies of B-cell lymphomas. We highlight the need for a minimum reporting standard to increase transparency in genomic research.},
langid = {english},
keywords = {Morinlab}
}
@online{drevalRevisitingReddyDLBCL2023,
title = {Revisiting {{Reddy}}: {{A DLBCL Do-over}}},
shorttitle = {Revisiting {{Reddy}}},
author = {Dreval, Kostiantyn and Cruz, Manuela and Rushton, Christopher and Liuta, Nina and Mirhosseini, Houman Layegh and Brown, Callum and Morin, Ryan D. and Consortium, the GAMBL},
date = {2023-11-22},
eprinttype = {bioRxiv},
eprintclass = {Contradictory Results},
pages = {2023.11.21.567983},
doi = {10.1101/2023.11.21.567983},
url = {https://www.biorxiv.org/content/10.1101/2023.11.21.567983v1},
urldate = {2024-01-24},
abstract = {The 2017 study by Reddy et al described the comprehensive characterization of somatic drivers of diffuse large B-cell lymphoma using whole exome sequencing.1 After additional large studies relying on exome or whole genome sequencing were published, several oddities unique to the Reddy results have emerged. Seeking to explain the discrepancies, we reanalyzed their data using established open-source pipelines. This revealed thousands of mutations that could not be independently reproduced by these pipelines and a larger set of high-quality mutations that were not reported by Reddy. This caused an artificial under-representation of the mutation prevalence in many genes including clinically relevant hot spots affecting EZH2 and CD79B. More generally, the study had an under-representation of mutations in DLBCL genes that disproportionately affected genes known to have the highest mutation rates. The missing variants and the spurious variants can be attributed to distinct problems with the analytical approaches employed in that study. Our analysis also identified strong associations between mutations and patient outcome including TP53, KMT2D and PIM1, which were not found in the Reddy study. Overall, we demonstrate that this combination of errors influenced many of the central novel findings from their study rendering their results largely non-replicable. The full results of our analyses are included as supplemental items as a resource for other researchers with an interest in the genetics of B-cell lymphomas.},
langid = {english},
pubstate = {preprint}
}
@article{duanFBXO11TargetsBCL62011,
title = {{{FBXO11}} Targets {{BCL6}} for Degradation and Is Inactivated in Diffuse Large {{B-cell}} Lymphomas.},
author = {Duan, Shanshan and Cermak, Lukas and Pagan, Julia K and Rossi, Mario and Martinengo, Cinzia and family=Celle, given=Paola Francia, prefix=di, useprefix=true and Chapuy, Bjoern and Shipp, Margaret and Chiarle, Roberto and Pagano, Michele},
date = {2011-11},
journaltitle = {Nature}
}
@article{duboisNextGenerationSequencing2016,
title = {Next {{Generation Sequencing}} in {{Diffuse Large B Cell Lymphoma Highlights Molecular Divergence}} and {{Therapeutic Opportunities}}: A {{LYSA Study}}.},
author = {Dubois, Sydney and Viailly, Pierre-Julien and Mareschal, Sylvain and Bohers, Elodie and Bertrand, Philippe and Ruminy, Philippe and Maingonnat, Catherine and Jais, Jean-Philippe and Peyrouze, Pauline and Figeac, Martin and Molina, Thierry J and Desmots, Fabienne and Fest, Thierry and Haioun, Corinne and Lamy, Thierry and Copie-Bergman, Christiane and Briere, Josette and Petrella, Tony and Canioni, Danielle and Fabiani, Bettina and Coiffier, Bertrand and Delarue, Richard and Peyrade, Frederic and Bosly, Andre and Andre, Marc and Ketterer, Nicolas and Salles, Gilles and Tilly, Hervé and Leroy, Karen and Jardin, Fabrice},
date = {2016-01},
journaltitle = {Clin Cancer Res},
pages = {clincanres.2305.2015}
}
@article{dunsCharacterizationDLBCLPMBL2021,
title = {Characterization of {{DLBCL}} with a {{PMBL}} Gene Expression Signature},
author = {Duns, Gerben and Viganò, Elena and Ennishi, Daisuke and Sarkozy, Clementine and Hung, Stacy S. and Chavez, Elizabeth and Takata, Katsuyoshi and Rushton, Christopher and Jiang, Aixiang and Ben-Neriah, Susana and Woolcock, Bruce W. and Slack, Graham W. and Hsi, Eric D. and Craig, Jeffrey W. and Hilton, Laura K. and Shah, Sohrab P. and Farinha, Pedro and Mottok, Anja and Gascoyne, Randy D. and Morin, Ryan D. and Savage, Kerry J. and Scott, David W. and Steidl, Christian},
date = {2021-07-15},
journaltitle = {Blood},
shortjournal = {Blood},
volume = {138},
number = {2},
eprint = {33684939},
eprinttype = {pmid},
pages = {136--148},
issn = {1528-0020},
doi = {10.1182/blood.2020007683},
abstract = {Primary mediastinal large B-cell lymphoma (PMBL) is a type of aggressive B-cell lymphoma that typically affects young adults, characterized by presence of a bulky anterior mediastinal mass. Lymphomas with gene expression features of PMBL have been described in nonmediastinal sites, raising questions about how these tumors should be classified. Here, we investigated whether these nonmediastinal lymphomas are indeed PMBLs or instead represent a distinct group within diffuse large B-cell lymphoma (DLBCL). From a cohort of 325 de novo DLBCL cases, we identified tumors from patients without evidence of anterior mediastinal involvement that expressed a PMBL expression signature (nm-PMBLsig+; n = 16; 5\%). A majority of these tumors expressed MAL and CD23, proteins typically observed in bona fide PMBL (bf-PMBL). Evaluation of clinical features of nm-PMBLsig+ cases revealed close associations with DLBCL, and a majority displayed a germinal center B cell-like cell of origin (GCB). In contrast to patients with bf-PMBL, patients with nm-PMBLsig+ presented at an older age and did not show pleural disease, and bone/bone marrow involvement was observed in 3 cases. However, although clinically distinct from bf-PMBL, nm-PMBLsig+ tumors resembled bf-PMBL at the molecular level, with upregulation of immune response, JAK-STAT, and NF-κB signatures. Mutational analysis revealed frequent somatic gene mutations in SOCS1, IL4R, ITPKB, and STAT6, as well as CD83 and BIRC3, with the latter genes significantly more frequently affected than in GCB DLBCL or bf-PMBL. Our data establish nm-PMBLsig+ lymphomas as a group within DLBCL with distinct phenotypic and genetic features. These findings may have implications for gene expression- and mutation-based subtyping of aggressive B-cell lymphomas and related targeted therapies.},
langid = {english},
keywords = {Adolescent,Adult,Aged,Aged 80 and over,B-Lymphocytes,DNA Copy Number Variations,DNA Mutational Analysis,Female,Gene Expression Profiling,Gene Expression Regulation Leukemic,HEK293 Cells,Humans,Immune Evasion,Immunophenotyping,Janus Kinases,Lymphoma Large B-Cell Diffuse,Lymphoma Non-Hodgkin,Male,Mediastinal Neoplasms,Middle Aged,Mutation,Receptors Interleukin-4,Somatic Hypermutation Immunoglobulin,STAT Transcription Factors,Young Adult}
}
@article{engelsPolypyrimidineTractBinding2012,
title = {Polypyrimidine {{Tract Binding Protein}} ({{hnRNP I}}) {{Is Possibly}} a {{Conserved Modulator}} of {{miRNA-Mediated Gene Regulation}}},
author = {Engels, Bart and Jannot, Guillaume and Remenyi, Judit and Simard, Martin J. and Hutvagner, György},
date = {2012-03-09},
journaltitle = {PLOS ONE},
shortjournal = {PLOS ONE},
volume = {7},
number = {3},
pages = {e33144},
publisher = {Public Library of Science},
issn = {1932-6203},
doi = {10.1371/journal.pone.0033144},
url = {https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0033144},
urldate = {2022-09-28},
abstract = {MiRNAs can regulate gene expression through versatile mechanisms that result in increased or decreased expression of the targeted mRNA and it could effect the expression of thousands of protein in a particular cell. An increasing body of evidence suggest that miRNAs action can be modulated by proteins that bind to the same 3′UTRs that are targeted by miRNAs, suggesting that other factors apart from miRNAs and their target sites determine miRNA-modulation of gene expression. We applied an affinity purification protocol using biotinylated let-7 miRNA inhibitor to isolate proteins that are involved in let-7 mediated gene regulation that resulted in an affinity purification of Polypyrimidine Tract Binding protein (PTB). Here we show that PTB interacts with miRNAs and human Argonaute 2 (hAgo2) through RNA as well as identified potential mammalian cellular targets that are co-regulated by PTB and hAgo2. In addition, using genetic approach, we have demonstrated that PTB genetically interacts with Caenorhabditis elegans let-7 indicating a conserved role for PTB in miRNA-mediated gene regulation.},
langid = {english},
keywords = {Affinity purification,Caenorhabditis elegans,Gene regulation,HeLa cells,Immunoprecipitation,MicroRNAs,RNA-binding proteins,Small interfering RNA}
}
@article{ennishiDoubleHitGeneExpression2019,
title = {Double-{{Hit Gene Expression Signature Defines}} a {{Distinct Subgroup}} of {{Germinal Center B-Cell-Like Diffuse Large B-Cell Lymphoma}}},
author = {Ennishi, Daisuke and Jiang, Aixiang and Boyle, Merrill and Collinge, Brett and Grande, Bruno M. and Ben-Neriah, Susana and Rushton, Christopher and Tang, Jeffrey and Thomas, Nicole and Slack, Graham W. and Farinha, Pedro and Takata, Katsuyoshi and Miyata-Takata, Tomoko and Craig, Jeffrey and Mottok, Anja and Meissner, Barbara and Saberi, Saeed and Bashashati, Ali and Villa, Diego and Savage, Kerry J. and Sehn, Laurie H. and Kridel, Robert and Mungall, Andrew J. and Marra, Marco A. and Shah, Sohrab P. and Steidl, Christian and Connors, Joseph M. and Gascoyne, Randy D. and Morin, Ryan D. and Scott, David W.},
date = {2019-01-20},
journaltitle = {Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology},
shortjournal = {J Clin Oncol},
volume = {37},
number = {3},
eprint = {30523716},
eprinttype = {pmid},
pages = {190--201},
issn = {1527-7755},
doi = {10.1200/JCO.18.01583},
abstract = {PURPOSE: High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (HGBL-DH/TH) has a poor outcome after standard chemoimmunotherapy. We sought to understand the biologic underpinnings of HGBL-DH/TH with BCL2 rearrangements (HGBL-DH/TH- BCL2) and diffuse large B-cell lymphoma (DLBCL) morphology through examination of gene expression. PATIENTS AND METHODS: We analyzed RNA sequencing data from 157 de novo germinal center B-cell-like (GCB)-DLBCLs, including 25 with HGBL-DH/TH- BCL2, to define a gene expression signature that distinguishes HGBL-DH/TH- BCL2 from other GCB-DLBCLs. To assess the genetic, molecular, and phenotypic features associated with this signature, we analyzed targeted resequencing, whole-exome sequencing, RNA sequencing, and immunohistochemistry data. RESULTS: We developed a 104-gene double-hit signature (DHITsig) that assigned 27\% of GCB-DLBCLs to the DHITsig-positive group, with only one half harboring MYC and BCL2 rearrangements (HGBL-DH/TH- BCL2). DHITsig-positive patients had inferior outcomes after rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone immunochemotherapy compared with DHITsig-negative patients (5-year time to progression rate, 57\% and 81\%, respectively; P {$<$} .001), irrespective of HGBL-DH/TH- BCL2 status. The prognostic value of DHITsig was confirmed in an independent validation cohort. DHITsig-positive tumors are biologically characterized by a putative non-light zone germinal center cell of origin and a distinct mutational landscape that comprises genes associated with chromatin modification. A new NanoString assay (DLBCL90) recapitulated the prognostic significance and RNA sequencing assignments. Validating the association with HGBL-DH/TH- BCL2, 11 of 25 DHITsig-positive-transformed follicular lymphomas were classified as HGBL-DH/TH- BCL2 compared with zero of 50 in the DHITsig-negative group. Furthermore, the DHITsig was shared with the majority of B-cell lymphomas with high-grade morphology tested. CONCLUSION: We have defined a clinically and biologically distinct subgroup of tumors within GCB-DLBCL characterized by a gene expression signature of HGBL-DH/TH- BCL2. This knowledge has been translated into an assay applicable to routinely available biopsy samples, which enables exploration of its utility to guide patient management.},
langid = {english},
pmcid = {PMC6804880},
keywords = {Adult,Aged,Aged 80 and over,Antibodies Monoclonal Murine-Derived,Antineoplastic Combined Chemotherapy Protocols,Cyclophosphamide,Doxorubicin,Female,Gene Rearrangement,Germinal Center,Humans,Lymphoma B-Cell,Lymphoma Large B-Cell Diffuse,Male,Middle Aged,Morinlab,Prednisone,Prognosis,Proto-Oncogene Proteins c-bcl-2,Proto-Oncogene Proteins c-myc,Rituximab,RNA Neoplasm,Transcriptome,Vincristine,Young Adult}
}
@article{ennishiGeneticProfilingMYC2017,
title = {Genetic Profiling of {{MYC}} and {{BCL2}} in Diffuse Large {{B-cell}} Lymphoma Determines Cell-of-Origin-Specific Clinical Impact.},
author = {Ennishi, Daisuke and Mottok, Anja and Ben-Neriah, Susana and Shulha, Hennady P and Farinha, Pedro and Chan, Fong Chun and Meissner, Barbara and Boyle, Merrill and Hother, Christoffer and Kridel, Robert and Lai, Daniel and Saberi, Saeed and Bashashati, Ali and Shah, Sohrab P and Morin, Ryan D and Marra, Marco A and Savage, Kerry J and Sehn, Laurie H and Steidl, Christian and Connors, Joseph M and Gascoyne, Randy D and Scott, David W},
date = {2017-05},
journaltitle = {Blood},
volume = {129},
number = {20},
pages = {2760--2770}
}
@article{fabbriAnalysisChronicLymphocytic2011,
title = {Analysis of the Chronic Lymphocytic Leukemia Coding Genome: Role of {{NOTCH1}} Mutational Activation},
shorttitle = {Analysis of the Chronic Lymphocytic Leukemia Coding Genome},
author = {Fabbri, Giulia and Rasi, Silvia and Rossi, Davide and Trifonov, Vladimir and Khiabanian, Hossein and Ma, Jing and Grunn, Adina and Fangazio, Marco and Capello, Daniela and Monti, Sara and Cresta, Stefania and Gargiulo, Ernesto and Forconi, Francesco and Guarini, Anna and Arcaini, Luca and Paulli, Marco and Laurenti, Luca and Larocca, Luigi M. and Marasca, Roberto and Gattei, Valter and Oscier, David and Bertoni, Francesco and Mullighan, Charles G. and Foá, Robin and Pasqualucci, Laura and Rabadan, Raul and Dalla-Favera, Riccardo and Gaidano, Gianluca},
date = {2011-07-04},
journaltitle = {The Journal of Experimental Medicine},
shortjournal = {J. Exp. Med.},
volume = {208},
number = {7},
eprint = {21670202},
eprinttype = {pmid},
pages = {1389--1401},
issn = {1540-9538},
doi = {10.1084/jem.20110921},
abstract = {The pathogenesis of chronic lymphocytic leukemia (CLL), the most common leukemia in adults, is still largely unknown. The full spectrum of genetic lesions that are present in the CLL genome, and therefore the number and identity of dysregulated cellular pathways, have not been identified. By combining next-generation sequencing and copy number analysis, we show here that the typical CLL coding genome contains {$<$}20 clonally represented gene alterations/case, including predominantly nonsilent mutations, and fewer copy number aberrations. These analyses led to the discovery of several genes not previously known to be altered in CLL. Although most of these genes were affected at low frequency in an expanded CLL screening cohort, mutational activation of NOTCH1, observed in 8.3\% of CLL at diagnosis, was detected at significantly higher frequency during disease progression toward Richter transformation (31.0\%), as well as in chemorefractory CLL (20.8\%). Consistent with the association of NOTCH1 mutations with clinically aggressive forms of the disease, NOTCH1 activation at CLL diagnosis emerged as an independent predictor of poor survival. These results provide initial data on the complexity of the CLL coding genome and identify a dysregulated pathway of diagnostic and therapeutic relevance.},
langid = {english},
pmcid = {PMC3135373},
keywords = {Adult,Aged,Disease Progression,Drug Resistance Neoplasm,Female,Gene Dosage,Gene Expression Regulation Neoplastic,Genes Immunoglobulin Heavy Chain,Genome Human,Humans,Leukemia Lymphocytic Chronic B-Cell,Male,Middle Aged,Mutation,Polymorphism Single Nucleotide,Prognosis,Receptor Notch1,Treatment Failure}
}
@article{fahiminiyaPolyadenylationSiteVariant2015,
title = {A Polyadenylation Site Variant Causes Transcript-Specific {{BMP1}} Deficiency and Frequent Fractures in Children},
author = {Fahiminiya, Somayyeh and Al-Jallad, Hadil and Majewski, Jacek and Palomo, Telma and Moffatt, Pierre and Roschger, Paul and Klaushofer, Klaus and Glorieux, Francis H. and Rauch, Frank},
date = {2015-01-15},
journaltitle = {Human Molecular Genetics},
shortjournal = {Human Molecular Genetics},
volume = {24},
number = {2},
pages = {516--524},
issn = {0964-6906},
doi = {10.1093/hmg/ddu471},
url = {https://doi.org/10.1093/hmg/ddu471},
urldate = {2022-10-25},
abstract = {We had previously published the clinical characteristics of a bone fragility disorder in children that was characterized mainly by lower extremity fractures and a mineralization defect in bone tissue but not on the growth plate level. We have now performed whole-exome sequencing on four unrelated individuals with this phenotype. Three individuals were homozygous for a nucleotide change in BMP1, affecting the polyadenylation signal of the transcript that codes for the short isoform of BMP1 (BMP1-1) (c.*241T\>C). In skin fibroblasts of these individuals, we found low levels of BMP1-1 transcript and protein. The fourth individual was compound heterozygous for the c.*241T\>C variant in BMP1-1 and a variant in BMP1 exon 15 (c.2107G\>C) that affected splicing in both BMP1-1 and the long isoform of BMP1 (BMP1-3). Both the homozygous 3′UTR variant and the compound heterozygous variants were associated with impaired procollagen type I C-propeptide cleavage, as the amount of free C-propeptide in the supernatant of skin fibroblasts was less than in controls. Peripheral quantitative computed tomography showed that all individuals had elevated volumetric cortical bone mineral density. Assessment of iliac bone samples by histomorphometry and quantitative backscattered electron imaging indicated that the onset of mineralization at bone formation sites was delayed, but that mineralized matrix was hypermineralized. These results show that isolated lack of BMP1-1 causes bone fragility in children.}
}
@article{fatehchandTolllikeReceptorLigands2016,
title = {Toll-like {{Receptor}} 4 {{Ligands Down-regulate Fcγ Receptor IIb}} ({{FcγRIIb}}) via {{MARCH3 Protein-mediated Ubiquitination}}.},
author = {Fatehchand, Kavin and Ren, Li and Elavazhagan, Saranya and Fang, Huiqing and Mo, Xiaokui and Vasilakos, John P and Dietsch, Gregory N and Hershberg, Robert M and Tridandapani, Susheela and Butchar, Jonathan P},
date = {2016-02},
journaltitle = {J Biol Chem},
volume = {291},
number = {8},
pages = {3895--3904}
}
@article{faveroSequenzaAllelespecificCopy2015,
title = {Sequenza: Allele-Specific Copy Number and Mutation Profiles from Tumor Sequencing Data},
shorttitle = {Sequenza},
author = {Favero, F. and Joshi, T. and Marquard, A. M. and Birkbak, N. J. and Krzystanek, M. and Li, Q. and Szallasi, Z. and Eklund, A. C.},
date = {2015-01},
journaltitle = {Annals of Oncology: Official Journal of the European Society for Medical Oncology},
shortjournal = {Ann Oncol},
volume = {26},
number = {1},
eprint = {25319062},
eprinttype = {pmid},
pages = {64--70},
issn = {1569-8041},
doi = {10.1093/annonc/mdu479},
abstract = {BACKGROUND: Exome or whole-genome deep sequencing of tumor DNA along with paired normal DNA can potentially provide a detailed picture of the somatic mutations that characterize the tumor. However, analysis of such sequence data can be complicated by the presence of normal cells in the tumor specimen, by intratumor heterogeneity, and by the sheer size of the raw data. In particular, determination of copy number variations from exome sequencing data alone has proven difficult; thus, single nucleotide polymorphism (SNP) arrays have often been used for this task. Recently, algorithms to estimate absolute, but not allele-specific, copy number profiles from tumor sequencing data have been described. MATERIALS AND METHODS: We developed Sequenza, a software package that uses paired tumor-normal DNA sequencing data to estimate tumor cellularity and ploidy, and to calculate allele-specific copy number profiles and mutation profiles. We applied Sequenza, as well as two previously published algorithms, to exome sequence data from 30 tumors from The Cancer Genome Atlas. We assessed the performance of these algorithms by comparing their results with those generated using matched SNP arrays and processed by the allele-specific copy number analysis of tumors (ASCAT) algorithm. RESULTS: Comparison between Sequenza/exome and SNP/ASCAT revealed strong correlation in cellularity (Pearson's r = 0.90) and ploidy estimates (r = 0.42, or r = 0.94 after manual inspecting alternative solutions). This performance was noticeably superior to previously published algorithms. In addition, in artificial data simulating normal-tumor admixtures, Sequenza detected the correct ploidy in samples with tumor content as low as 30\%. CONCLUSIONS: The agreement between Sequenza and SNP array-based copy number profiles suggests that exome sequencing alone is sufficient not only for identifying small scale mutations but also for estimating cellularity and inferring DNA copy number aberrations.},
langid = {english},
pmcid = {PMC4269342},
keywords = {Algorithms,Alleles,Base Sequence,cancer genomics,copy number alterations,DNA Copy Number Variations,Exome,Gene Dosage,High-Throughput Nucleotide Sequencing,Humans,Mutation,mutations,Neoplasms,next-generation sequencing,Polymorphism Single Nucleotide,Sequence Analysis DNA,software,Software}
}
@article{fentonFollicularLymphomaNovel2002,
title = {Follicular Lymphoma with a Novel t(14;18) Breakpoint Involving the Immunoglobulin Heavy Chain Switch Mu Region Indicates an Origin from Germinal Center {{B}} Cells},
author = {Fenton, James A. L. and Vaandrager, Jan-Willem and Aarts, Wilhelmina M. and Bende, Richard J. and Heering, Karel and family=Dijk, given=Martin, prefix=van, useprefix=true and Morgan, Gareth and family=Noesel, given=Carel J. M., prefix=van, useprefix=true and Schuuring, Ed and Kluin, Philip M.},
date = {2002-01-15},
journaltitle = {Blood},
shortjournal = {Blood},
volume = {99},
number = {2},
eprint = {11781262},
eprinttype = {pmid},
pages = {716--718},
issn = {0006-4971},
doi = {10.1182/blood.v99.2.716},
abstract = {With the use of DNA-fiber fluorescent in situ hybridization, a BCL2 protein positive follicular lymphoma with a novel BCL2 breakpoint involving the immunoglobulin heavy chain (IGH) switch mu (S(mu)) region instead of the J(H) or D(H) gene segments was identified. Sequence analysis showed that the genomic breakpoint is localized between the S(mu) region of the IGH complex and the first intron of BCL2. Reverse-transcriptase polymerase chain reaction showed expression of a unique hybrid IGH-BCL2 transcript involving the transcription initiation site I(mu). Sequence analysis of the V(H) region of the functional nontranslocated IGH allele showed multiple shared somatic mutations but also a high intraclonal variation (53 differences in 15 clones), compatible with the lymphoma cells staying in or re-entering the germinal center. This is the first example of a t(14;18) translocation that results from an illegitimate IGH class-switch recombination during the germinal center B-cell stage.},
langid = {english},
keywords = {Aged,B-Lymphocytes,Base Sequence,Cell Differentiation,Chromosome Breakage,Chromosomes Human Pair 14,Chromosomes Human Pair 16,DNA Neoplasm,Embryonal Carcinoma Stem Cells,Female,Genes bcl-2,Genes Immunoglobulin,Genes Switch,Germinal Center,Humans,Immunoglobulin Heavy Chains,Lymphoma Follicular,Molecular Sequence Data,Neoplastic Stem Cells,Oncogene Proteins Fusion,Reverse Transcriptase Polymerase Chain Reaction,RNA Messenger,RNA Neoplasm,Somatic Hypermutation Immunoglobulin,Translocation Genetic}
}
@article{fernandez-rodriguezMYD88L265PMutation2014,
title = {{{MYD88}} ({{L265P}}) Mutation Is an Independent Prognostic Factor for Outcome in Patients with Diffuse Large {{B-cell}} Lymphoma.},
author = {Fernández-Rodríguez, C and Bellosillo, B and García-García, M and Sánchez-González, B and Gimeno, E and Vela, M C and Serrano, S and Besses, C and Salar, A},
date = {2014-10},
journaltitle = {Leukemia},
volume = {28},
number = {10},
pages = {2104--2106}
}
@article{ferreroKMT2DMutationsTP532019,
title = {{{KMT2D}} Mutations and {{TP53}} Disruptions Are Poor Prognostic Biomarkers in Mantle Cell Lymphoma Receiving High-Dose Therapy: A {{FIL}} Study},
shorttitle = {{{KMT2D}} Mutations and {{TP53}} Disruptions Are Poor Prognostic Biomarkers in Mantle Cell Lymphoma Receiving High-Dose Therapy},
author = {Ferrero, Simone and Rossi, Davide and Rinaldi, Andrea and Bruscaggin, Alessio and Spina, Valeria and Eskelund, Christian W. and Evangelista, Andrea and Moia, Riccardo and Kwee, Ivo and Dahl, Christina and Rocco, Alice Di and Stefoni, Vittorio and Diop, Fary and Favini, Chiara and Ghione, Paola and Mahmoud, Abdurraouf Mokhtar and Schipani, Mattia and Kolstad, Arne and Barbero, Daniela and Novero, Domenico and Paulli, Marco and Zamò, Alberto and Jerkeman, Mats and family=Silva, given=Maria Gomez, prefix=da, useprefix=false and Santoro, Armando and Molinari, Annalia and Ferreri, Andres and Grønbæk, Kirsten and Piccin, Andrea and Cortelazzo, Sergio and Bertoni, Francesco and Ladetto, Marco and Gaidano, Gianluca},
date = {2019-09-19},
journaltitle = {Haematologica},
eprint = {31537689},
eprinttype = {pmid},
issn = {0390-6078, 1592-8721},
doi = {10.3324/haematol.2018.214056},
url = {http://www.haematologica.org/content/early/2019/09/17/haematol.2018.214056},
urldate = {2019-12-24},
abstract = {In recent years, the outcome of mantle cell lymphoma has improved, especially in younger patients, receiving cytarabine-containing chemoimmunotherapy and autologous stem cell transplantation. Nevertheless, a proportion of mantle cell lymphoma patients still experience early failure. To identify biomarkers anticipating failure of intensive chemotherapy in mantle cell lymphoma, we performed target resequencing and DNA profiling of purified tumor samples collected from patients enrolled in the prospective FIL-MCL0208 phase III trial (high-dose chemoimmunotherapy followed by autologous transplantation and randomized lenalidomide maintenance). Mutations of KMT2D and disruption of TP53 by deletion or mutation associated with an increased risk of progression and death, both in univariate and multivariate analysis. By adding KMT2D mutations and TP53 disruption to the MIPI-c backbone, we derived a new prognostic index, the MIPI-genetic. The MIPI-g improved the model discrimination ability compared to the MIPI-c alone, defining three risk groups: i) low-risk patients (4-years progression free survival and overall survival of 72.0\% and 94.5\%); ii) intermediate-risk patients (4-years progression free survival and overall survival of 42.2\% and 65.8\%) and iii) high-risk patients (4-years progression free survival and overall survival of 11.5\% and 44.9\%). Our results: i) confirm that TP53 disruption identifies a high-risk population characterized by poor sensitivity to conventional or intensified chemotherapy; ii) provide the pivotal evidence that patients harboring KMT2D mutations share the same poor outcome as patients harboring TP53 disruption; and iii) allow to develop a tool for the identification of high-risk mantle cell lymphoma patients for whom novel therapeutic strategies need to be investigated. (Trial registered at clinicaltrials.gov identifier: NCT02354313)},
langid = {english}
}
@article{filipitsCyclinD3Predictive,
title = {Cyclin {{D3}} Is a Predictive and Prognostic Factor in Diffuse Large {{B-cell}} Lymphoma},
author = {Filipits, Martin and Jaeger, Ulrich and Pohl, Gudrun and Stranzl, Thomas and Simonitsch, Ingrid and Kaider, Alexandra and Skrabs, Cathrin and Pirker, Robert},
journaltitle = {Clin Cancer Res},
volume = {8},
number = {3},
pages = {729--733}
}
@article{fisetteHnRNPA1HnRNP2010,
title = {{{hnRNP A1}} and {{hnRNP H}} Can Collaborate to Modulate 5′ Splice Site Selection},
author = {Fisette, Jean-François and Toutant, Johanne and Dugré-Brisson, Samuel and Desgroseillers, Luc and Chabot, Benoit},
date = {2010-01},
journaltitle = {RNA},
shortjournal = {RNA},
volume = {16},
number = {1},
eprint = {19926721},
eprinttype = {pmid},
pages = {228--238},
issn = {1355-8382},
doi = {10.1261/rna.1890310},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2802032/},
urldate = {2022-09-27},
abstract = {The mammalian proteins hnRNP A1 and hnRNP H control many splicing decisions in viral and cellular primary transcripts. To explain some of these activities, we have proposed that self-interactions between bound proteins create an RNA loop that represses internal splice sites while simultaneously activating the external sites that are brought in closer proximity. Here we show that a variety of hnRNP H binding sites can affect 5′ splice site selection. The addition of two sets of hnRNP H sites in a model pre-mRNA modulates 5′ splice site selection cooperatively, consistent with the looping model. Notably, binding sites for hnRNP A1 and H on the same pre-mRNA can similarly collaborate to modulate 5′ splice site selection. The C-terminal portion of hnRNP H that contains the glycine-rich domains (GRD) is essential for splicing activity, and it can be functionally replaced by the GRD of hnRNP A1. Finally, we used the bioluminescence resonance energy transfer (BRET) technology to document the existence of homotypic and heterotypic interactions between hnRNP H and hnRNP A1 in live cells. Overall, our study suggests that interactions between different hnRNP proteins bound to distinct locations on a pre-mRNA can change its conformation to affect splicing decisions.},
pmcid = {PMC2802032}
}
@article{gallardoHnRNPHaploinsufficientTumor2015,
title = {{{hnRNP K}} Is a Haploinsufficient Tumor Suppressor That Regulates Proliferation and Differentiation Programs in Hematologic Malignancies},
author = {Gallardo, Miguel and Lee, Hun Ju and Zhang, Xiaorui and Bueso-Ramos, Carlos and Pageon, Laura R. and McArthur, Mark and Multani, Asha and Nazha, Aziz and Manshouri, Taghi and Parker-Thornburg, Jan and Rapado, Inmaculada and Quintas-Cardama, Alfonso and Kornblau, Steven M. and Martinez-Lopez, Joaquin and Post, Sean M.},
date = {2015-10-12},
journaltitle = {Cancer cell},
shortjournal = {Cancer Cell},
volume = {28},
number = {4},
eprint = {26412324},
eprinttype = {pmid},
pages = {486--499},
issn = {1535-6108},
doi = {10.1016/j.ccell.2015.09.001},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4652598/},
urldate = {2022-09-25},
abstract = {hnRNP K regulates cellular programs and changes in its expression and mutational status have been implicated in neoplastic malignancies. To directly examine its role in tumorigenesis, we generated a mouse model harboring an Hnrnpk knock-out allele (Hnrnpk+/−). Hnrnpk haploinsufficiency resulted in reduced survival, increased tumor formation, genomic instability, and the development of transplantable hematopoietic neoplasms with myeloproliferation. Reduced hnRNP K expression attenuated p21 activation, downregulated C/EBP levels, and activated STAT3 signaling. Additionally, analysis of samples from primary acute myeloid leukemia patients harboring a partial deletion of chromosome 9 revealed a significant decrease in HNRNPK expression. Together, these data implicate hnRNP K in the development of hematological disorders and suggest hnRNP K acts as a tumor suppressor.},
pmcid = {PMC4652598}
}
@article{gallardoUncoveringRoleRNABinding2019,
title = {Uncovering the {{Role}} of {{RNA-Binding Protein hnRNP K}} in {{B-Cell Lymphomas}}},
author = {Gallardo, Miguel and Malaney, Prerna and Aitken, Marisa J L and Zhang, Xiaorui and Link, Todd M and Shah, Vrutant and Alybayev, Sanzhar and Wu, Meng-Han and Pageon, Laura R and Ma, Huaxian and Jacamo, Rodrigo and Yu, Li and Xu-Monette, Zijun Y and Steinman, Haley and Lee, Hun Ju and Sarbassov, Dos and Rapado, Inmaculada and Barton, Michelle C and Martinez-Lopez, Joaquin and Bueso-Ramos, Carlos and Young, Ken H and Post, Sean M},
date = {2019-05-11},
journaltitle = {JNCI Journal of the National Cancer Institute},
shortjournal = {J Natl Cancer Inst},
volume = {112},
number = {1},
eprint = {31077320},
eprinttype = {pmid},
pages = {95--106},
issn = {0027-8874},
doi = {10.1093/jnci/djz078},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489062/},
urldate = {2022-09-22},
abstract = {Background Heterogeneous nuclear ribonucleoprotein K (hnRNP~K) is an RNA-binding protein that is aberrantly expressed in cancers. We and others have previously shown that reduced hnRNP~K expression downmodulates tumor-suppressive programs. However, overexpression of hnRNP~K is the more commonly observed clinical phenomenon, yet its functional consequences and clinical significance remain unknown. Methods Clinical implications of hnRNP~K overexpression were examined through immunohistochemistry on samples from patients with diffuse large B-cell lymphoma who did not harbor MYC alterations (n\,=\,75). A novel transgenic mouse model that overexpresses hnRNP~K specifically in B cells was generated to directly examine the role of hnRNP~K overexpression in mice (three transgenic lines). Molecular consequences of hnRNP~K overexpression were determined through proteomics, formaldehyde-RNA-immunoprecipitation sequencing, and biochemical assays. Therapeutic response to BET-bromodomain inhibition in the context of hnRNP~K overexpression was evaluated in vitro and in vivo (n\,=\,3 per group). All statistical tests were two-sided. Results hnRNP~K is overexpressed in diffuse large B-cell lymphoma patients without MYC genomic alterations. This overexpression is associated with dismal overall survival and progression-free survival (P\,{$<$}\,.001). Overexpression of hnRNP~K in transgenic mice resulted in the development of lymphomas and reduced survival (P\,{$<$}\,.001 for all transgenic lines; Line 171[n\,=\,30]: hazard ratio [HR]\,=\,64.23, 95\% confidence interval [CI]\,=\,26.1 to 158.0; Line 173 [n\,=\,31]: HR\,=\,25.27, 95\% CI\,=\,10.3 to 62.1; Line 177 [n\,=\,25]: HR\,=\,119.5, 95\% CI\,=\,42.7 to 334.2, compared with wild-type mice). Clinical samples, mouse models, global screening assays, and biochemical studies revealed that hnRNP~K’s oncogenic potential stems from its ability to posttranscriptionally and translationally regulate MYC. Consequently, Hnrnpk overexpression renders cells sensitive to BET-bromodomain-inhibition in both in vitro and transplantation models, which represents a strategy for mitigating hnRNP~K-mediated c-Myc activation in patients. Conclusion Our findings indicate that hnRNP~K is a bona fide oncogene when overexpressed and represents a novel mechanism for c-Myc activation in the absence of MYC lesions.},
pmcid = {PMC7489062}
}
@article{ganapathiGeneticLandscapeDural2016,
title = {The Genetic Landscape of Dural Marginal Zone Lymphomas},
author = {Ganapathi, Karthik A. and Jobanputra, Vaidehi and Iwamoto, Fabio and Jain, Preti and Chen, Jinli and Cascione, Luciano and Nahum, Odelia and Levy, Brynn and Xie, Yi and Khattar, Pallavi and Hoehn, Daniela and Bertoni, Francesco and Murty, Vundavalli V. and Pittaluga, Stefania and Jaffe, Elaine S. and Alobeid, Bachir and Mansukhani, Mahesh M. and Bhagat, Govind},
date = {2016-05-27},
year = {2016},
journaltitle = {Oncotarget},
volume = {7},
number = {28},
pages = {43052--43061},
publisher = {Impact Journals},
issn = {1949-2553},
doi = {10.18632/oncotarget.9678},
abstract = {https://doi.org/10.18632/oncotarget.9678 Karthik A. Ganapathi, Vaidehi Jobanputra, Fabio Iwamoto, Preti Jain, Jinli Chen, Luciano Cascione, Odelia Nahum, Brynn Levy, Yi Xie, Pallavi Khattar, Daniela...},
langid = {english}
}
@article{gaoIntegrativeAnalysisComplex2013,
title = {Integrative Analysis of Complex Cancer Genomics and Clinical Profiles Using the {{cBioPortal}}},
author = {Gao, Jianjiong and Aksoy, Bülent Arman and Dogrusoz, Ugur and Dresdner, Gideon and Gross, Benjamin and Sumer, S. Onur and Sun, Yichao and Jacobsen, Anders and Sinha, Rileen and Larsson, Erik and Cerami, Ethan and Sander, Chris and Schultz, Nikolaus},
date = {2013-04-02},
journaltitle = {Science Signaling},
shortjournal = {Sci Signal},
volume = {6},
number = {269},
eprint = {23550210},
eprinttype = {pmid},
pages = {pl1},
issn = {1937-9145},
doi = {10.1126/scisignal.2004088},
abstract = {The cBioPortal for Cancer Genomics (http://cbioportal.org) provides a Web resource for exploring, visualizing, and analyzing multidimensional cancer genomics data. The portal reduces molecular profiling data from cancer tissues and cell lines into readily understandable genetic, epigenetic, gene expression, and proteomic events. The query interface combined with customized data storage enables researchers to interactively explore genetic alterations across samples, genes, and pathways and, when available in the underlying data, to link these to clinical outcomes. The portal provides graphical summaries of gene-level data from multiple platforms, network visualization and analysis, survival analysis, patient-centric queries, and software programmatic access. The intuitive Web interface of the portal makes complex cancer genomics profiles accessible to researchers and clinicians without requiring bioinformatics expertise, thus facilitating biological discoveries. Here, we provide a practical guide to the analysis and visualization features of the cBioPortal for Cancer Genomics.},
langid = {english},
pmcid = {PMC4160307},
keywords = {Gene Expression Profiling,Gene Regulatory Networks,Genetic Predisposition to Disease,Genomics,Humans,Information Storage and Retrieval,Internet,Neoplasms,Reproducibility of Results,Software}
}
@article{garapaty-raoIdentificationEZH2EZH12013,
title = {Identification of {{EZH2}} and {{EZH1 Small Molecule Inhibitors}} with {{Selective Impact}} on {{Diffuse Large B Cell Lymphoma Cell Growth}}},
author = {Garapaty-Rao, Shivani and Nasveschuk, Christopher and Gagnon, Alexandre and Chan, Eric Y and Sandy, Peter and Busby, Jennifer and Balasubramanian, Srividya and Campbell, Robert and Zhao, Feng and Bergeron, Louise and Audia, James E and Albrecht, Brian K and Harmange, Jean-Christophe and Cummings, Richard and Trojer, Patrick},
date = {2013-11},
journaltitle = {Chemistry \& Biology},
volume = {20},
number = {11},
pages = {1329--1339}
}
@article{garbatiHistoneAcetyltransferaseP300,
title = {Histone Acetyltransferase P300 Is a Coactivator for Transcription Factor {{REL}} and Is {{C-terminally}} Truncated in the Human Diffuse Large {{B-cell}} Lymphoma Cell Line {{RC-K8}}},
author = {Garbati, Michael and Alço, Gökçen and Gilmore, Thomas},
journaltitle = {Cancer Lett},
volume = {291},
number = {2},
pages = {237--245}
}
@article{garcia-ramirezCrebbpLossCooperates2017,
title = {Crebbp Loss Cooperates with {{Bcl2}} Overexpression to Promote Lymphoma in Mice},
author = {García-Ramírez, Idoia and Tadros, Saber and González-Herrero, Inés and Martín-Lorenzo, Alberto and Rodríguez-Hernández, Guillermo and Moore, Dalia and Ruiz-Roca, Lucía and Blanco, Oscar and Alonso-López, Diego and Rivas, Javier De Las and Hartert, Keenan and Duval, Romain and Klinkebiel, David and Bast, Martin and Vose, Julie and Lunning, Matthew and Fu, Kai and Greiner, Timothy and Rodrigues-Lima, Fernando and Jiménez, Rafael and Criado, Francisco Javier García and Cenador, María Begoña García and Brindle, Paul and Vicente-Dueñas, Carolina and Alizadeh, Ash and Sánchez-García, Isidro and Green, Michael R.},
date = {2017-05-11},
journaltitle = {Blood},
shortjournal = {Blood},
volume = {129},
number = {19},
eprint = {28288979},
eprinttype = {pmid},
pages = {2645--2656},
issn = {1528-0020},
doi = {10.1182/blood-2016-08-733469},
abstract = {CREBBP is targeted by inactivating mutations in follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). Here, we provide evidence from transgenic mouse models that Crebbp deletion results in deficits in B-cell development and can cooperate with Bcl2 overexpression to promote B-cell lymphoma. Through transcriptional and epigenetic profiling of these B cells, we found that Crebbp inactivation was associated with broad transcriptional alterations, but no changes in the patterns of histone acetylation at the proximal regulatory regions of these genes. However, B cells with Crebbp inactivation showed high expression of Myc and patterns of altered histone acetylation that were localized to intragenic regions, enriched for Myc DNA binding motifs, and showed Myc binding. Through the analysis of CREBBP mutations from a large cohort of primary human FL and DLBCL, we show a significant difference in the spectrum of CREBBP mutations in these 2 diseases, with higher frequencies of nonsense/frameshift mutations in DLBCL compared with FL. Together, our data therefore provide important links between Crebbp inactivation and Bcl2 dependence and show a role for Crebbp inactivation in the induction of Myc expression. We suggest this may parallel the role of CREBBP frameshift/nonsense mutations in DLBCL that result in loss of the protein, but may contrast the role of missense mutations in the lysine acetyltransferase domain that are more frequently observed in FL and yield an inactive protein.},
langid = {english},
pmcid = {PMC5428458},
keywords = {Animals,B-Lymphocytes,CREB-Binding Protein,Epigenesis Genetic,Gene Deletion,Gene Expression Regulation Neoplastic,Humans,Lymphoma Follicular,Lymphoma Large B-Cell Diffuse,Mice,Mice Transgenic,Mutation,Proto-Oncogene Proteins c-bcl-2}
}
@article{gargMCPIP1EndoribonucleaseActivity2015,
title = {{{MCPIP1 Endoribonuclease Activity Negatively Regulates Interleukin-17-Mediated Signaling}} and {{Inflammation}}},
author = {Garg, Abhishek V and Amatya, Nilesh and Chen, Kong and Cruz, J Agustin and Grover, Prerna and Whibley, Natasha and Conti, Heather R and Mir, Gerard Hernandez and Sirakova, Tatiana and Childs, Erin C and Smithgall, Thomas E and Biswas, Partha S and Kolls, Jay K and McGeachy, Mandy J and Kolattukudy, Pappachan E and Gaffen, Sarah L},
date = {2015-09},
journaltitle = {Immunity},
volume = {43},
number = {3},
pages = {475--487}
}
@article{gaudreauHeterogeneousNuclearRibonucleoprotein2016,
title = {Heterogeneous {{Nuclear Ribonucleoprotein L}} Is Required for the Survival and Functional Integrity of Murine Hematopoietic Stem Cells},
author = {Gaudreau, Marie-Claude and Grapton, Damien and Helness, Anne and Vadnais, Charles and Fraszczak, Jennifer and Shooshtarizadeh, Peiman and Wilhelm, Brian and Robert, François and Heyd, Florian and Möröy, Tarik},
date = {2016-06-07},
journaltitle = {Scientific Reports},
shortjournal = {Sci Rep},
volume = {6},
number = {1},
pages = {27379},
publisher = {Nature Publishing Group},
issn = {2045-2322},
doi = {10.1038/srep27379},
url = {https://www.nature.com/articles/srep27379},
urldate = {2022-10-04},
abstract = {The proliferation and survival of hematopoietic stem cells (HSCs) has to be strictly coordinated to ensure the timely production of all blood cells. Here we report that the splice factor and RNA binding protein hnRNP L (heterogeneous nuclear ribonucleoprotein L) is required for hematopoiesis, since its genetic ablation in mice reduces almost all blood cell lineages and causes premature death of the animals. In agreement with this, we observed that hnRNP L deficient HSCs lack both the ability to self-renew and foster hematopoietic differentiation in transplanted hosts. They also display mitochondrial dysfunction, elevated levels of γH2AX, are Annexin V positive and incorporate propidium iodide indicating that they undergo cell death. Lin-c-Kit+ fetal liver cells from hnRNP L deficient mice show high p53 protein levels and up-regulation of p53 target genes. In addition, cells lacking hnRNP L up-regulated the expression of the death receptors TrailR2 and CD95/Fas and show Caspase-3, Caspase-8 and Parp cleavage. Treatment with the pan-caspase inhibitor Z-VAD-fmk, but not the deletion of p53, restored cell survival in hnRNP L deficient cells. Our data suggest that hnRNP L is critical for the survival and functional integrity of HSCs by restricting the activation of caspase-dependent death receptor pathways.},
issue = {1},
langid = {english},
keywords = {Apoptosis,Haematopoietic stem cells}
}
@article{gautreySRSF3HnRNPH12015,
title = {{{SRSF3}} and {{hnRNP H1}} Regulate a Splicing Hotspot of {{HER2}} in Breast Cancer Cells},
author = {Gautrey, Hannah and Jackson, Claire and Dittrich, Anna-Lena and Browell, David and Lennard, Thomas and Tyson-Capper, Alison},
date = {2015-09-14},
journaltitle = {RNA Biology},
shortjournal = {RNA Biol},
volume = {12},
number = {10},
eprint = {26367347},
eprinttype = {pmid},
pages = {1139--1151},
issn = {1547-6286},
doi = {10.1080/15476286.2015.1076610},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4829299/},
urldate = {2022-09-28},
abstract = {Overexpression of the oncogene HER2 occurs in 20–30\% of invasive breast cancer and is associated with poor prognosis. A number of different splice variants of HER2 have been identified which produce functionally different proteins. Previously these splice variants have been investigated separately, but in the present study we collectively look at the expression and regulation of a group of HER2 splice variants produced by a splicing hotspot. Initial investigation in a cohort of tumor samples showed large variations in HER2 variant expression between patient samples. RNA interference studies identified 2 splicing factors involved in the regulation of splicing within this region, hnRNP H1 and SRSF3. siRNA targeting hnRNP H1 increases levels of X5 and the oncogenic variant Δ16HER2. Furthermore RNA chromatography assays demonstrated binding of hnRNP H1 to RNA in this region. Additionally the proto-oncogene SRSF3 was also identified as an important regulator of splicing with SRSF3 knockdown resulting in changes in all the splice variants located at the hotspot. Most notably knockdown of SRSF3 resulted in a switch from the oncogenic Δ16HER2 to p100 which inhibits cell proliferation. Binding of SRSF3 to RNA within this region was also demonstrated by RNA chromatography and more specifically 2 SRSF3 binding sites were identified within exon 15. SRSF3 and hnRNP H1 are the first splicing factors identified which regulate the production of these functionally distinct HER2 splice variants and therefore maybe important for the regulation of HER2 signaling.},
pmcid = {PMC4829299}
}
@article{gebauerActivatingMutationsAffecting2014,
title = {Activating Mutations Affecting the {{NF-kappa B}} Pathway and {{EZH2-mediated}} Epigenetic Regulation Are Rare Events in Primary Mediastinal Large {{B-cell}} Lymphoma},
author = {Gebauer, Niklas and Hardel, Tim Tristan and Gebauer, Judith and Bernard, Veronica and Merz, Hartmut and Feller, Alfred C. and Rades, Dirk and Biersack, Harald and Lehnert, Hendrik and Thorns, Christoph},
date = {2014-10},
journaltitle = {Anticancer Research},
shortjournal = {Anticancer Res},
volume = {34},
number = {10},
eprint = {25275047},
eprinttype = {pmid},
pages = {5503--5507},
issn = {1791-7530},
abstract = {BACKGROUND: Primary mediastinal large B-cell lymphoma (PMBL) is a distinct subtype of diffuse large B-cell lymphoma (DLBCL) frequently observed in young patients. High-dose immunochemotherapy constitutes the current therapeutic gold-standard, despite significant toxicity and serious late effects. Several hotspots harboring oncogenic gain-of-function mutations were recently shown to pose vital hallmarks in activated B-cell like (ABC-) (CD79B, CARD11 and MYD88) and germinal center like (GCB-) DLBCL (EZH2), respectively. Several promising targeted-therapy approaches, derived from these findings, are currently under development. MATERIALS AND METHODS: We thoroughly characterized a cohort of 25 untreated patients with de novo PMBL by immunohistochemical and cytogenetic means and assessed the prevalence of activating mutations affecting EZH2, CD79B and CARD11 utilizing a polymerase chain reaction (PCR)-based capillary sequencing approach. Moreover, the MYD88 p. L265P status was assessed by employing a pyrosequencing approach. RESULTS: PMBLs included in this study did not harbor any of the reported hotspot mutations activating the nuclear factor (NF)-kappa B signaling cascade or the EZH2-mediated epigenetic deregulation of gene expression. Immunohistochemical characterization revealed an ABC phenotype in 44\% (n=11) of cases. CONCLUSION: We report that genetic alterations of these genes are rare events in PMBL unlike other subtypes of DLBCL. Our findings suggest that a substantial subset of PMBL patients may benefit from treatment approaches targeting BCR-mediated activation of NF-kappa B.},
langid = {english},
keywords = {Adolescent,Adult,Aged,Aged 80 and over,CARD11,CD79B,Enhancer of Zeste Homolog 2 Protein,Epigenesis Genetic,EZH2,Female,Gene Expression Regulation Neoplastic,Humans,Lymphoma Large B-Cell Diffuse,Male,Mediastinal Neoplasms,Middle Aged,Mutation,Mutation Rate,MYD88,NF-kappa B,NFkappaB pathway,Oncogenes,Polycomb Repressive Complex 2,Primary mediastinal large B-cell lymphoma,Signal Transduction,Young Adult}
}
@article{golan-gerstlSplicingFactorHnRNP2011,
title = {Splicing Factor {{hnRNP A2}}/{{B1}} Regulates Tumor Suppressor Gene Splicing and Is an Oncogenic Driver in Glioblastoma},
author = {Golan-Gerstl, Regina and Cohen, Michal and Shilo, Asaf and Suh, Sung-Suk and Bakàcs, Arianna and Coppola, Luigi and Karni, Rotem},
date = {2011-07-01},
journaltitle = {Cancer Research},
shortjournal = {Cancer Res.},
volume = {71},
number = {13},
eprint = {21586613},
eprinttype = {pmid},
pages = {4464--4472},
issn = {1538-7445},
doi = {10.1158/0008-5472.CAN-10-4410},
abstract = {The process of alternative splicing is widely misregulated in cancer, but the contribution of splicing regulators to cancer development is largely unknown. In this study, we found that the splicing factor hnRNP A2/B1 is overexpressed in glioblastomas and is correlated with poor prognosis. Conversely, patients who harbor deletions of the HNRNPA2B1 gene show better prognosis than average. Knockdown of hnRNP A2/B1 in glioblastoma cells inhibited tumor formation in mice. In contrast, overexpression of hnRNP A2/B1 in immortal cells led to malignant transformation, suggesting that HNRNPA2B1 is a putative proto-oncogene. We then identified several tumor suppressors and oncogenes that are regulated by HNRNPA2B1, among them are c-FLIP, BIN1, and WWOX, and the proto-oncogene RON. Knockdown of RON inhibited hnRNP A2/B1 mediated transformation, which implied that RON is one of the mediators of HNRNPA2B1 oncogenic activity. Together, our results indicate that HNRNPA2B1 is a novel oncogene in glioblastoma and a potential new target for glioblastoma therapy.},
langid = {english},
keywords = {Alternative Splicing,Animals,Brain Neoplasms,Cell Line Tumor,Cell Transformation Neoplastic,Gene Dosage,Gene Expression Regulation Neoplastic,Gene Knockdown Techniques,Genes Tumor Suppressor,Glioblastoma,Heterogeneous-Nuclear Ribonucleoprotein Group A-B,Humans,Mice,NIH 3T3 Cells,Receptor Protein-Tyrosine Kinases,Up-Regulation}
}
@article{gomezUltraDeepSequencingReveals2023,
title = {Ultra-{{Deep Sequencing Reveals}} the {{Mutational Landscape}} of {{Classical Hodgkin Lymphoma}}},
author = {Gomez, Felicia and Fisk, Bryan and McMichael, Joshua F. and Mosior, Matthew and Foltz, Jennifer A. and Skidmore, Zachary L. and Duncavage, Eric J. and Miller, Christopher A. and Abel, Haley and Li, Yi-Shan and Russler-Germain, David A. and Krysiak, Kilannin and Watkins, Marcus P. and Ramirez, Cody A. and Schmidt, Alina and Martins Rodrigues, Fernanda and Trani, Lee and Khanna, Ajay and Wagner, Julia A. and Fulton, Robert S. and Fronick, Catrina C. and O'Laughlin, Michelle D. and Schappe, Timothy and Cashen, Amanda F. and Mehta-Shah, Neha and Kahl, Brad S. and Walker, Jason and Bartlett, Nancy L. and Griffith, Malachi and Fehniger, Todd A. and Griffith, Obi L.},
date = {2023-11-15},
journaltitle = {Cancer Research Communications},
shortjournal = {Cancer Res Commun},
volume = {3},
number = {11},
eprint = {37910143},
eprinttype = {pmid},
pages = {2312--2330},
issn = {2767-9764},
doi = {10.1158/2767-9764.CRC-23-0140},
abstract = {The malignant Hodgkin and Reed Sternberg (HRS) cells of classical Hodgkin lymphoma (cHL) are scarce in affected lymph nodes, creating a challenge to detect driver somatic mutations. As an alternative to cell purification techniques, we hypothesized that ultra-deep exome sequencing would allow genomic study of HRS cells, thereby streamlining analysis and avoiding technical pitfalls. To test this, 31 cHL tumor/normal pairs were exome sequenced to approximately 1,000× median depth of coverage. An orthogonal error-corrected sequencing approach verified {$>$}95\% of the discovered mutations. We identified mutations in genes novel to cHL including: CDH5 and PCDH7, novel stop gain mutations in IL4R, and a novel pattern of recurrent mutations in pathways regulating Hippo signaling. As a further application of our exome sequencing, we attempted to identify expressed somatic single-nucleotide variants (SNV) in single-nuclei RNA sequencing (snRNA-seq) data generated from a patient in our cohort. Our snRNA analysis identified a clear cluster of cells containing a somatic SNV identified in our deep exome data. This cluster has differentially expressed genes that are consistent with genes known to be dysregulated in HRS cells (e.g., PIM1 and PIM3). The cluster also contains cells with an expanded B-cell clonotype further supporting a malignant phenotype. This study provides proof-of-principle that ultra-deep exome sequencing can be utilized to identify recurrent mutations in HRS cells and demonstrates the feasibility of snRNA-seq in the context of cHL. These studies provide the foundation for the further analysis of genomic variants in large cohorts of patients with cHL. SIGNIFICANCE: Our data demonstrate the utility of ultra-deep exome sequencing in uncovering somatic variants in Hodgkin lymphoma, creating new opportunities to define the genes that are recurrently mutated in this disease. We also show for the first time the successful application of snRNA-seq in Hodgkin lymphoma and describe the expression profile of a putative cluster of HRS cells in a single patient.},
langid = {english},
pmcid = {PMC10648575},
keywords = {High-Throughput Nucleotide Sequencing,Hodgkin Disease,Humans,Mutation,Reed-Sternberg Cells,RNA Small Nuclear}
}
@article{gongSequentialInverseDysregulation2021,
title = {Sequential Inverse Dysregulation of the {{RNA}} Helicases {{DDX3X}} and {{DDX3Y}} Facilitates {{MYC-driven}} Lymphomagenesis},
author = {Gong, Chun and Krupka, Joanna A. and Gao, Jie and Grigoropoulos, Nicholas F. and Giotopoulos, George and Asby, Ryan and Screen, Michael and Usheva, Zelvera and Cucco, Francesco and Barrans, Sharon and Painter, Daniel and Zaini, Nurmahirah Binte Mohammed and Haupl, Björn and Bornelöv, Susanne and Ruiz De Los Mozos, Igor and Meng, Wei and Zhou, Peixun and Blain, Alex E. and Forde, Sorcha and Matthews, Jamie and Khim Tan, Michelle Guet and Burke, G. A. Amos and Sze, Siu Kwan and Beer, Philip and Burton, Cathy and Campbell, Peter and Rand, Vikki and Turner, Suzanne D. and Ule, Jernej and Roman, Eve and Tooze, Reuben and Oellerich, Thomas and Huntly, Brian J. and Turner, Martin and Du, Ming-Qing and Samarajiwa, Shamith A. and Hodson, Daniel J.},
year = {2021},
journaltitle = {Molecular Cell},
shortjournal = {Molecular Cell},
issn = {1097-2765},
doi = {10.1016/j.molcel.2021.07.041},
abstract = {DDX3X is a ubiquitously expressed RNA helicase involved in multiple stages of RNA biogenesis. DDX3X is frequently mutated in Burkitt lymphoma, but the functional basis for this is unknown. Here, we show that loss-of-function DDX3X mutations are also enriched in MYC-translocated diffuse large B cell lymphoma and reveal functional cooperation between mutant DDX3X and MYC. DDX3X promotes the translation of mRNA encoding components of the core translational machinery, thereby driving global protein synthesis. Loss-of-function DDX3X mutations moderate MYC-driven global protein synthesis, thereby buffering MYC-induced proteotoxic stress during early lymphomagenesis. Established lymphoma cells restore full protein synthetic capacity by aberrant expression of DDX3Y, a Y chromosome homolog, the expression of which is normally restricted to the testis. These findings show that DDX3X loss of function can buffer MYC-driven proteotoxic stress and highlight the capacity of male B cell lymphomas to then compensate for this loss by ectopic DDX3Y expression.},
langid = {english},
keywords = {Burkitt lymphoma,DDX3X,germinal center,MYC,proteotoxic stress,RNA helicase,translation}
}
@article{grandeGenomewideDiscoverySomatic2019,
title = {Genome-Wide Discovery of Somatic Coding and Noncoding Mutations in Pediatric Endemic and Sporadic {{Burkitt}} Lymphoma},
author = {Grande, Bruno M. and Gerhard, Daniela S. and Jiang, Aixiang and Griner, Nicholas B. and Abramson, Jeremy S. and Alexander, Thomas B. and Allen, Hilary and Ayers, Leona W. and Bethony, Jeffrey M. and Bhatia, Kishor and Bowen, Jay and Casper, Corey and Choi, John Kim and Culibrk, Luka and Davidsen, Tanja M. and Dyer, Maureen A. and Gastier-Foster, Julie M. and Gesuwan, Patee and Greiner, Timothy C. and Gross, Thomas G. and Hanf, Benjamin and Harris, Nancy Lee and He, Yiwen and Irvin, John D. and Jaffe, Elaine S. and Jones, Steven J. M. and Kerchan, Patrick and Knoetze, Nicole and Leal, Fabio E. and Lichtenberg, Tara M. and Ma, Yussanne and Martin, Jean Paul and Martin, Marie-Reine and Mbulaiteye, Sam M. and Mullighan, Charles G. and Mungall, Andrew J. and Namirembe, Constance and Novik, Karen and Noy, Ariela and Ogwang, Martin D. and Omoding, Abraham and Orem, Jackson and Reynolds, Steven J. and Rushton, Christopher K. and Sandlund, John T. and Schmitz, Roland and Taylor, Cynthia and Wilson, Wyndham H. and Wright, George W. and Zhao, Eric Y. and Marra, Marco A. and Morin, Ryan D. and Staudt, Louis M.},
year = {2019},
journaltitle = {Blood},
shortjournal = {Blood},
volume = {133},
number = {12},
pages = {1313--1324},
issn = {0006-4971},
doi = {10.1182/blood-2018-09-871418},
langid = {english},
pmcid = {PMC6428665},
keywords = {Morinlab}
}
@article{greenHitandrunLymphomagenesisBcl6,
title = {Hit-and-Run Lymphomagenesis by the {{Bcl6}} Oncogene.},
author = {Green, Michael R and Vicente-Dueñas, Carolina and Alizadeh, Ash A and Sánchez-García, Isidro},
journaltitle = {Cell Cycle (Georgetown, Tex.)},
volume = {13},
number = {12},
pages = {1831--1832}
}
@article{greenTransientExpressionBcl601,
title = {Transient Expression of {{Bcl6}} Is Sufficient for Oncogenic Function and Induction of Mature {{B-cell}} Lymphoma},
author = {Green, Michael R and family=as, given=Carolina Vicente-Due, prefix=ntilde, useprefix=false and Romero-Camarero, Isabel and Liu, Chih Long and Dai, Bo and family=Herrero, given=In eacute s Gonz, prefix=aacute, useprefix=true and family=rez, given=Idoia Garc, prefix=iacute a-Ram iacute, useprefix=false and Alonso-Escudero, Esther and Iqbal, Javeed and Chan, Wing C and Campos-Sánchez, Elena and Orfao, Alberto and family=Pintado, given=Bel, prefix=eacute n, useprefix=false and Flores, Teresa and Blanco, Oscar and family=nez, given=Rafael Jim, prefix=eacute, useprefix=false and family=Climent, given=Jose Angel Mart, prefix=iacute, useprefix=true and family=Criado, given=Francisco Javier Garc, prefix=iacute a, useprefix=false and family=Cenador, given=Mar iacute a Bego ntilde a Garc, prefix=iacute a, useprefix=false and Zhao, Shuchun and Natkunam, Yasodha and Lossos, Izidore S and Majeti, Ravindra and Melnick, Ari and family=Cobaleda, given=C, prefix=eacute sar, useprefix=false and Alizadeh, Ash A and family=a, given=Isidro S, prefix=aacute nchez-Garc iacute, useprefix=false},
date = {0001},
journaltitle = {Nature communications},
volume = {5},
pages = {1--13}
}
@article{guCirclizeImplementsEnhances2014,
title = {Circlize Implements and Enhances Circular Visualization in {{R}}},
author = {Gu, Zuguang and Gu, Lei and Eils, Roland and Schlesner, Matthias and Brors, Benedikt},
date = {2014-10-01},
journaltitle = {Bioinformatics},
shortjournal = {Bioinformatics},
volume = {30},
number = {19},
pages = {2811--2812},
issn = {1367-4803},
doi = {10.1093/bioinformatics/btu393},
url = {https://doi.org/10.1093/bioinformatics/btu393},
urldate = {2023-12-16},
abstract = {Summary: Circular layout is an efficient way for the visualization of huge amounts of genomic information. Here we present the circlize package, which provides an implementation of circular layout generation in R as well as an enhancement of available software. The flexibility of this package is based on the usage of low-level graphics functions such that self-defined high-level graphics can be easily implemented by users for specific purposes. Together with the seamless connection between the powerful computational and visual environment in R, circlize gives users more convenience and freedom to design figures for better understanding genomic patterns behind multi-dimensional data. Availability and implementation: ~circlize is available at the Comprehensive R Archive Network (CRAN): http://cran.r-project.org/web/packages/circlize/Contact: ~b.brors@dkfz.deSupplementary information: ~Supplementary data are available at Bioinformatics online.}
}
@article{gunawardanaRecurrentSomaticMutations2014,
title = {Recurrent Somatic Mutations of {{PTPN1}} in Primary Mediastinal {{B}} Cell Lymphoma and {{Hodgkin}} Lymphoma},
author = {Gunawardana, Jay and Chan, Fong Chun and Telenius, Adèle and Woolcock, Bruce and Kridel, Robert and Tan, King L. and Ben-Neriah, Susana and Mottok, Anja and Lim, Raymond S. and Boyle, Merrill and Rogic, Sanja and Rimsza, Lisa M. and Guiter, Chrystelle and Leroy, Karen and Gaulard, Philippe and Haioun, Corinne and Marra, Marco A. and Savage, Kerry J. and Connors, Joseph M. and Shah, Sohrab P. and Gascoyne, Randy D. and Steidl, Christian},
date = {2014-04},
journaltitle = {Nature Genetics},
shortjournal = {Nat Genet},
volume = {46},
number = {4},
eprint = {24531327},
eprinttype = {pmid},
pages = {329--335},
issn = {1546-1718},
doi = {10.1038/ng.2900},
abstract = {Classical Hodgkin lymphoma and primary mediastinal B cell lymphoma (PMBCL) are related lymphomas sharing pathological, molecular and clinical characteristics. Here we discovered by whole-genome and whole-transcriptome sequencing recurrent somatic coding-sequence mutations in the PTPN1 gene. Mutations were found in 6 of 30 (20\%) Hodgkin lymphoma cases, in 6 of 9 (67\%) Hodgkin lymphoma-derived cell lines, in 17 of 77 (22\%) PMBCL cases and in 1 of 3 (33\%) PMBCL-derived cell lines, consisting of nonsense, missense and frameshift mutations. We demonstrate that PTPN1 mutations lead to reduced phosphatase activity and increased phosphorylation of JAK-STAT pathway members. Moreover, silencing of PTPN1 by RNA interference in Hodgkin lymphoma cell line KM-H2 resulted in hyperphosphorylation and overexpression of downstream oncogenic targets. Our data establish PTPN1 mutations as new drivers in lymphomagenesis.},
langid = {english},
keywords = {Gene Expression Profiling,Gene Knockdown Techniques,Genomics,HEK293 Cells,High-Throughput Nucleotide Sequencing,Hodgkin Disease,Humans,Immunohistochemistry,In Situ Hybridization Fluorescence,Kaplan-Meier Estimate,Laser Capture Microdissection,Lymphoma B-Cell,Mediastinal Neoplasms,Mutation,Phosphorylation,Protein Tyrosine Phosphatase Non-Receptor Type 1,Real-Time Polymerase Chain Reaction,RNA Interference}
}
@article{habibMycStimulatesLymphocyte2007,
title = {Myc Stimulates {{B}} Lymphocyte Differentiation and Amplifies Calcium Signaling},
author = {Habib, Tania and Park, Heon and Tsang, Mark and family=Alborán, given=Ignacio Moreno, prefix=de, useprefix=true and Nicks, Andrea and Wilson, Leslie and Knoepfler, Paul S. and Andrews, Sarah and Rawlings, David J. and Eisenman, Robert N. and Iritani, Brian M.},
date = {2007-11-19},
journaltitle = {The Journal of Cell Biology},
shortjournal = {J Cell Biol},
volume = {179},
number = {4},
eprint = {17998397},
eprinttype = {pmid},
pages = {717--731},
issn = {0021-9525},
doi = {10.1083/jcb.200704173},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2080907/},
urldate = {2022-10-06},
abstract = {Deregulated expression of the Myc family of transcription factors (c-, N-, and L-myc) contributes to the development of many cancers by a mechanism believed to involve the stimulation of cell proliferation and inhibition of differentiation. However, using B cell–specific c-/N-myc double-knockout mice and Eμ-myc transgenic mice bred onto genetic backgrounds (recombinase-activating gene 2−/− and Btk−/− Tec−/−) whereby B cell development is arrested, we show that Myc is necessary to stimulate both proliferation and differentiation in primary B cells. Moreover, Myc expression results in sustained increases in intracellular Ca2+ ([Ca2+]i), which is required for Myc to stimulate B cell proliferation and differentiation. The increase in [Ca2+]i correlates with constitutive nuclear factor of activated T cells (NFAT) nuclear translocation, reduced Ca2+ efflux, and decreased expression of the plasma membrane Ca2+–adenosine triphosphatase (PMCA) efflux pump. Our findings demonstrate a revised model whereby Myc promotes both proliferation and differentiation, in part by a remarkable mechanism whereby Myc amplifies Ca2+ signals, thereby enabling the concurrent expression of Myc- and Ca2+-regulated target genes.},
pmcid = {PMC2080907}
}
@article{hackenSplicingModulationSensitizes2018,
title = {Splicing Modulation Sensitizes Chronic Lymphocytic Leukemia Cells to Venetoclax by Remodeling Mitochondrial Apoptotic Dependencies},
author = {family=Hacken, given=Elisa, prefix=ten, useprefix=false and Valentin, Rebecca and Regis, Fara Faye D. and Sun, Jing and Yin, Shanye and Werner, Lillian and Deng, Jing and Gruber, Michaela and Wong, Jessica and Zheng, Mei and Gill, Amy L. and Seiler, Michael and Smith, Peter and Thomas, Michael and Buonamici, Silvia and Ghia, Emanuela M. and Kim, Ekaterina and Rassenti, Laura Z. and Burger, Jan A. and Kipps, Thomas J. and Meyerson, Matthew L. and Bachireddy, Pavan and Wang, Lili and Reed, Robin and Neuberg, Donna and Carrasco, Ruben D. and Brooks, Angela N. and Letai, Anthony and Davids, Matthew S. and Wu, Catherine J.},
date = {2018-10-04},
journaltitle = {JCI Insight},
shortjournal = {JCI Insight},
volume = {3},
number = {19},
eprint = {0},
eprinttype = {pmid},
issn = {0021-9738},
doi = {10.1172/jci.insight.121438},
url = {https://insight.jci.org/articles/view/121438},
urldate = {2019-12-21},
langid = {english}
}
@article{halldorsdottirImpactTP53Mutation2011,
title = {Impact of {{TP53}} Mutation and 17p Deletion in Mantle Cell Lymphoma},
author = {Halldórsdóttir, A. M. and Lundin, A. and Murray, F. and Mansouri, L. and Knuutila, S. and Sundström, C. and Laurell, A. and Ehrencrona, H. and Sander, B. and Rosenquist, R.},
date = {2011-12},
journaltitle = {Leukemia},
volume = {25},
number = {12},
pages = {1904--1908},
issn = {1476-5551},
doi = {10.1038/leu.2011.162},
url = {https://www.nature.com/articles/leu2011162},
urldate = {2019-12-21},
langid = {english}
}
@article{hiltonRelapseTimingAssociated2023,
title = {Relapse {{Timing Is Associated With Distinct Evolutionary Dynamics}} in {{Diffuse Large B-Cell Lymphoma}}},
author = {Hilton, Laura K. and Ngu, Henry S. and Collinge, Brett and Dreval, Kostiantyn and Ben-Neriah, Susana and Rushton, Christopher K. and Wong, Jasper C.H. and Cruz, Manuela and Roth, Andrew and Boyle, Merrill and Meissner, Barbara and Slack, Graham W. and Farinha, Pedro and Craig, Jeffrey W. and Gerrie, Alina S. and Freeman, Ciara L. and Villa, Diego and Rodrigo, Judith A. and Song, Kevin and Crump, Michael and Shepherd, Lois and Hay, Annette E. and Kuruvilla, John and Savage, Kerry J. and Kridel, Robert and Karsan, Aly and Marra, Marco A. and Sehn, Laurie H. and Steidl, Christian and Morin, Ryan D. and Scott, David W.},
date = {2023-09},
journaltitle = {Journal of Clinical Oncology},
shortjournal = {JCO},
volume = {41},
number = {25},
pages = {4164--4177},
publisher = {Wolters Kluwer},
issn = {0732-183X},
doi = {10.1200/JCO.23.00570},
url = {https://ascopubs.org/doi/full/10.1200/JCO.23.00570},
urldate = {2023-10-21},
abstract = {PURPOSE Diffuse large B-cell lymphoma (DLBCL) is cured in more than 60\% of patients, but outcomes remain poor for patients experiencing disease progression or relapse (refractory or relapsed DLBCL [rrDLBCL]), particularly if these events occur early. Although previous studies examining cohorts of rrDLBCL have identified features that are enriched at relapse, few have directly compared serial biopsies to uncover biological and evolutionary dynamics driving rrDLBCL. Here, we sought to confirm the relationship between relapse timing and outcomes after second-line (immuno)chemotherapy and determine the evolutionary dynamics that underpin that relationship. PATIENTS AND METHODS Outcomes were examined in a population-based cohort of 221 patients with DLBCL who experienced progression/relapse after frontline treatment and were treated with second-line (immuno)chemotherapy with an intention-to-treat with autologous stem-cell transplantation (ASCT). Serial DLBCL biopsies from a partially overlapping cohort of 129 patients underwent molecular characterization, including whole-genome or whole-exome sequencing in 73 patients. RESULTS Outcomes to second-line therapy and ASCT are superior for late relapse ({$>$}2 years postdiagnosis) versus primary refractory ({$<$}9 months) or early relapse (9-24 months). Diagnostic and relapse biopsies were mostly concordant for cell-of-origin classification and genetics-based subgroup. Despite this concordance, the number of mutations exclusive to each biopsy increased with time since diagnosis, and late relapses shared few mutations with their diagnostic counterpart, demonstrating a branching evolution pattern. In patients with highly divergent tumors, many of the same genes acquired new mutations independently in each tumor, suggesting that the earliest mutations in a shared precursor cell constrain tumor evolution toward the same genetics-based subgroups at both diagnosis and relapse. CONCLUSION These results suggest that late relapses commonly represent genetically distinct and chemotherapy-naïve disease and have implications for optimal patient management.},
keywords = {Morinlab}
}
@article{hirtRiskFollicularLymphoma2015,
title = {Risk of Follicular Lymphoma Associated with {{BCL2}} Translocations in Peripheral Blood},
author = {Hirt, Carsten and Camargo, M. Constanza and Yu, Kelly J. and Hewitt, Stephen M. and Dölken, Gottfried and Rabkin, Charles S.},
date = {2015},
journaltitle = {Leukemia \& Lymphoma},
shortjournal = {Leuk Lymphoma},
volume = {56},
number = {9},
eprint = {25549806},
eprinttype = {pmid},
pages = {2625--2629},
issn = {1029-2403},
doi = {10.3109/10428194.2014.999324},
abstract = {Many adults have circulating lymphocytes with the BCL2 gene translocation characteristic of follicular lymphoma. We therefore conducted a nested case-control study of incident lymphomas with peripheral blood obtained a median 4.9 years pre-diagnosis from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Overall, 13 of 26 cases of lymphoma and 14 of 47 controls had BCL2 major breakpoint region (MBR) translocations in pre-diagnosis blood (odds ratio [OR] = 2.8). Nine cases had BCL2-MBR-positive tumors; eight of these nine had BCL2-MBR translocations in paired blood versus five of the 17 with BCL2-MBR-negative tumors (p = 0.01). Comparing both tumor types to controls, blood BCL2-MBR translocations had a strong, statistically significant association with BCL2-MBR-positive tumors (OR = 26), but not with BCL2-MBR-negative tumors (OR = 0.9). All eight BCL2-MBR-positive tumors with pre-diagnosis BCL2 translocations were clonally related to these circulating cells, based on similarity of recombination sequences. These data indicate that blood BCL2-MBR translocations represent lymphoma precursor clones with malignant potential.},
langid = {english},
pmcid = {PMC5819878},
keywords = {Aged,Aged 80 and over,Blood Cells,Case-Control Studies,Chromosome Breakpoints,Chromosomes Human Pair 14,Chromosomes Human Pair 18,Female,Gene Dosage,Genes Immunoglobulin,Genetic Association Studies,Genetic Predisposition to Disease,Humans,Lymphoma and Hodgkin disease,Lymphoma Follicular,Male,Middle Aged,molecular genetics,Odds Ratio,Population Surveillance,prognostication,Proto-Oncogene Proteins c-bcl-2,Risk,Translocation Genetic,United States}
}
@article{hirtRiskFollicularLymphoma2015a,
title = {Risk of Follicular Lymphoma Associated with {{BCL2}} Translocations in Peripheral Blood},
author = {Hirt, Carsten and Camargo, M. Constanza and Yu, Kelly J. and Hewitt, Stephen M. and Dölken, Gottfried and Rabkin, Charles S.},
date = {2015},
journaltitle = {Leukemia \& Lymphoma},
shortjournal = {Leuk Lymphoma},
volume = {56},
number = {9},
eprint = {25549806},
eprinttype = {pmid},
pages = {2625--2629},
issn = {1029-2403},
doi = {10.3109/10428194.2014.999324},
abstract = {Many adults have circulating lymphocytes with the BCL2 gene translocation characteristic of follicular lymphoma. We therefore conducted a nested case-control study of incident lymphomas with peripheral blood obtained a median 4.9 years pre-diagnosis from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Overall, 13 of 26 cases of lymphoma and 14 of 47 controls had BCL2 major breakpoint region (MBR) translocations in pre-diagnosis blood (odds ratio [OR] = 2.8). Nine cases had BCL2-MBR-positive tumors; eight of these nine had BCL2-MBR translocations in paired blood versus five of the 17 with BCL2-MBR-negative tumors (p = 0.01). Comparing both tumor types to controls, blood BCL2-MBR translocations had a strong, statistically significant association with BCL2-MBR-positive tumors (OR = 26), but not with BCL2-MBR-negative tumors (OR = 0.9). All eight BCL2-MBR-positive tumors with pre-diagnosis BCL2 translocations were clonally related to these circulating cells, based on similarity of recombination sequences. These data indicate that blood BCL2-MBR translocations represent lymphoma precursor clones with malignant potential.},
langid = {english},
pmcid = {PMC5819878},
keywords = {Aged,Aged 80 and over,Blood Cells,Case-Control Studies,Chromosome Breakpoints,Chromosomes Human Pair 14,Chromosomes Human Pair 18,Female,Gene Dosage,Genes Immunoglobulin,Genetic Association Studies,Genetic Predisposition to Disease,Humans,Lymphoma and Hodgkin disease,Lymphoma Follicular,Male,Middle Aged,molecular genetics,Odds Ratio,Population Surveillance,prognostication,Proto-Oncogene Proteins c-bcl-2,Risk,Translocation Genetic,United States}
}
@article{hitzOutcomePatientsPrimary2015,
title = {Outcome of Patients with Primary Refractory Diffuse Large {{B}} Cell Lymphoma after {{R-CHOP}} Treatment},
author = {Hitz, Felicitas and Connors, J. M. and Gascoyne, R. D. and Hoskins, P. and Moccia, A. and Savage, K. J. and Sehn, L. H. and Shenkier, T. and Villa, D. and Klasa, R.},
date = {2015},
journaltitle = {Annals of Hematology},
volume = {94},
number = {11},
eprint = {26246466},
eprinttype = {pmid},
pages = {1839--1843},
issn = {0939-5555},
doi = {10.1007/s00277-015-2467-z},
url = {http://dx.doi.org/10.1007/s00277-015-2467-z},
abstract = {Primary refractory diffuse large B cell lymphoma (DLBCL) following R-CHOP chemotherapy is a major concern. We identified 1126 patients with DLBCL treated with R-CHOP from 2000 to 2009, of whom 166 (15 \%) had primary refractory disease. Of the 75/166 (45 \%) who were age {$<$}70 years and had been planned for stage-directed curative therapy, 43 (57 \%) were primary nonresponders and 32 (43 \%) relapsed within 3 months of completing R-CHOP. Thirty of 75 (40 \%) patients had serious comorbidity and organ dysfunction precluding intensive treatment and had palliative treatment only. Twelve of 45 (27 \%) patients responded to second-line treatment and underwent ASCT. The median overall survival for the 75 patients was 10 months with only seven patients alive without evidence of disease at follow-up ranging from 14 to 106 months. Primary refractory DLBCL after R-CHOP has a very poor outcome with only anecdotal survivors independent of the intended treatment approach.}
}
@article{holienMYCAmplificationsMyeloma2015,
title = {{{MYC}} Amplifications in Myeloma Cell Lines: Correlation with {{MYC-inhibitor}} Efficacy},
shorttitle = {{{MYC}} Amplifications in Myeloma Cell Lines},
author = {Holien, Toril and Misund, Kristine and Olsen, Oddrun Elise and Baranowska, Katarzyna Anna and Buene, Glenn and Børset, Magne and Waage, Anders and Sundan, Anders},
date = {2015-06-02},
journaltitle = {Oncotarget},
shortjournal = {Oncotarget},
volume = {6},
number = {26},
eprint = {26087190},
eprinttype = {pmid},
pages = {22698--22705},
issn = {1949-2553},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4673192/},
urldate = {2022-10-05},
abstract = {In multiple myeloma, elevated MYC expression is related to disease initiation and progression. We found that in myeloma cell lines, MYC gene amplifications were common and correlated with MYC mRNA and protein. In primary cell samples MYC mRNA levels were also relatively high; however gene copy number alterations were uncommon. Elevated levels of MYC in primary myeloma cells have been reported to arise from complex genetic aberrations and are more common than previously thought. Thus, elevated MYC expression is achieved differently in myeloma cell lines and primary cells. Sensitivity of myeloma cell lines to the MYC inhibitor 10058-F4 correlated with MYC expression, supporting that the activity of 10058-F4 was through specific inhibition of MYC.},
pmcid = {PMC4673192}
}
@article{honigbergBrutonTyrosineKinase2010,
title = {The {{Bruton}} Tyrosine Kinase Inhibitor {{PCI-32765}} Blocks {{B-cell}} Activation and Is Efficacious in Models of Autoimmune Disease and {{B-cell}} Malignancy},
author = {Honigberg, Lee A. and Smith, Ashley M. and Sirisawad, Mint and Verner, Erik and Loury, David and Chang, Betty and Li, Shyr and Pan, Zhengying and Thamm, Douglas H. and Miller, Richard A. and Buggy, Joseph J.},
date = {2010-07-20},
journaltitle = {Proceedings of the National Academy of Sciences of the United States of America},
shortjournal = {Proc Natl Acad Sci U S A},
volume = {107},
number = {29},
eprint = {20615965},
eprinttype = {pmid},
pages = {13075--13080},
issn = {1091-6490},
doi = {10.1073/pnas.1004594107},
abstract = {Activation of the B-cell antigen receptor (BCR) signaling pathway contributes to the initiation and maintenance of B-cell malignancies and autoimmune diseases. The Bruton tyrosine kinase (Btk) is specifically required for BCR signaling as demonstrated by human and mouse mutations that disrupt Btk function and prevent B-cell maturation at steps that require a functional BCR pathway. Herein we describe a selective and irreversible Btk inhibitor, PCI-32765, that is currently under clinical development in patients with B-cell non-Hodgkin lymphoma. We have used this inhibitor to investigate the biologic effects of Btk inhibition on mature B-cell function and the progression of B cell-associated diseases in vivo. PCI-32765 blocked BCR signaling in human peripheral B cells at concentrations that did not affect T cell receptor signaling. In mice with collagen-induced arthritis, orally administered PCI-32765 reduced the level of circulating autoantibodies and completely suppressed disease. PCI-32765 also inhibited autoantibody production and the development of kidney disease in the MRL-Fas(lpr) lupus model. Occupancy of the Btk active site by PCI-32765 was monitored in vitro and in vivo using a fluorescent affinity probe for Btk. Active site occupancy of Btk was tightly correlated with the blockade of BCR signaling and in vivo efficacy. Finally, PCI-32765 induced objective clinical responses in dogs with spontaneous B-cell non-Hodgkin lymphoma. These findings support Btk inhibition as a therapeutic approach for the treatment of human diseases associated with activation of the BCR pathway.},
langid = {english},
pmcid = {PMC2919935},
keywords = {Administration Oral,Agammaglobulinaemia Tyrosine Kinase,Animals,Arthritis Experimental,Autoantibodies,Autoimmune Diseases,B-Lymphocytes,Benzofurans,Disease Models Animal,Dogs,Humans,Lymphocyte Activation,lymphoma,Lymphoma B-Cell,Mice,Protein Kinase Inhibitors,Protein-Tyrosine Kinases,Pyrazoles,Pyrimidines,Receptors Antigen B-Cell,Signal Transduction,Treatment Outcome,X-linked agammaglobulinemia}
}
@article{honoreHeterogeneousNuclearRibonucleoproteins2004,
title = {Heterogeneous Nuclear Ribonucleoproteins {{F}} and {{H}}/{{H}}' Show Differential Expression in Normal and Selected Cancer Tissues},
author = {Honoré, Bent and Baandrup, Ulrik and Vorum, Henrik},
date = {2004-03-10},
journaltitle = {Experimental Cell Research},
shortjournal = {Exp. Cell Res.},
volume = {294},
number = {1},
eprint = {14980514},
eprinttype = {pmid},
pages = {199--209},
issn = {0014-4827},
doi = {10.1016/j.yexcr.2003.11.011},
abstract = {The heterogeneous nuclear ribonucleoproteins (hnRNPs) F and H/H', containing the quasi-RNA recognition motif (qRRM) domains, are implicated in several steps of pre-mRNA processing and in cellular differentiation. We have compared a set of tissues and found striking differences in their levels of expression as well as in the nuclear versus the cytoplasmic distribution. Generally, hnRNP F is broadly expressed in many tissues with extremely strong expression in the prostate gland while hnRNP H/H' shows a more restricted degree of expression with low expression in some tissues, for example, liver, exocrine acini of the pancreas, thyroid gland and heart. At the cellular level, hnRNP F is, with few exceptions, predominantly expressed in the cytoplasm while hnRNP H/H' is more abundant in the nuclei. A quite pronounced heterogeneous expression pattern is seen in the proximal tubules of the kidney where hnRNP F is present at moderate cytoplasmic levels while hnRNP H/H' is undetectable, whereas both proteins are more evenly expressed in distal tubules and collecting ducts. Generally, tumor tissues reveal a broad expression of hnRNP F in the nuclei as well as in the cytoplasm while hnRNP H/H' is expressed at higher levels in the nuclei than in the cytoplasm. Up-regulation of hnRNP H/H' is found in a few tissues that normally express low cytoplasmic levels of hnRNP H/H', for example, adenocarcinoma of the pancreas, hepatocellular carcinoma and gastric carcinoma. hnRNP F is down-regulated in hepatocellular carcinoma and up-regulated in gastric carcinoma. The present study indicates the important potential role of this subset of hnRNPs on the gene expression in many tissues.},
langid = {english},
keywords = {Adenocarcinoma,Carcinoma Hepatocellular,Heterogeneous-Nuclear Ribonucleoprotein Group F-H,Humans,Immunohistochemistry,Liver Neoplasms,Neoplasms,Pancreatic Neoplasms,Tissue Distribution,Tumor Cells Cultured}
}
@article{huang1418Defines2002,
title = {The t(14;18) Defines a Unique Subset of Diffuse Large {{B-cell}} Lymphoma with a Germinal Center {{B-cell}} Gene Expression Profile},
author = {Huang, James Z and Sanger, Warren G and Greiner, Timothy C and Staudt, Louis M and Weisenburger, Dennis D and Pickering, Diane L and Lynch, James C and Armitage, James O and Warnke, Roger A and Alizadeh, Ash A and Lossos, Izidore S and Levy, Ronald and Chan, Wing C},
date = {2002-04},
journaltitle = {Blood},
volume = {99},
number = {7},
pages = {2285--2290}
}
@article{huangPCBP1RegulatesTranscription2021,
title = {{{PCBP1}} Regulates the Transcription and Alternative Splicing of Metastasis‑related Genes and Pathways in Hepatocellular Carcinoma},
author = {Huang, Shuai and Luo, Kai and Jiang, Li and Zhang, Xu-Dong and Lv, Ying-Hao and Li, Ren-Feng},
date = {2021-12-02},
journaltitle = {Scientific Reports},
shortjournal = {Sci Rep},
volume = {11},
number = {1},
eprint = {34857818},
eprinttype = {pmid},
pages = {23356},
issn = {2045-2322},
doi = {10.1038/s41598-021-02642-z},
abstract = {PCBP1 is a multifunctional RNA-binding protein (RBP) expressed in most human cells and is involved in posttranscriptional gene regulation. PCBP1 regulates the alternative splicing, translation and RNA stability of many cancer-related genes and has been identified as a potential tumour suppressor gene. PCBP1 inhibits the invasion of hepatocellular carcinoma (HCC) cells, but there are few studies on the specific regulatory target and mechanism of RBPs in HCC, and it is unclear whether PCBP1 plays a role in tumour metastasis as a splicing factor. We analysed the regulation of gene expression by PCBP1 at the transcriptional level. We obtained and analysed PCBP1-knockdown RNA-seq data and eCLIP-seq data of PCBP1 in HepG2 cells and found that PCBP1 widely regulates the alternative splicing and expression of genes enriched in cancer-related pathways, including extracellular matrix, cell adhesion, small molecule metabolic process and apoptosis. We validated five regulated alternative splicing events affected by PCBP1 using RT-qPCR and found that there was a significant difference in the expression of APOC1 and SPHK1 between tumour and normal tissues. In this study, we provided convincing evidence that human PCBP1 profoundly regulates the splicing of genes associated with tumour metastasis. These findings provide new insight into potential markers or therapeutic targets for HCC treatment.},
langid = {english},
pmcid = {PMC8640068},
keywords = {Alternative Splicing,Biomarkers Tumor,Carcinoma Hepatocellular,DNA-Binding Proteins,Gene Expression Profiling,Gene Expression Regulation Neoplastic,Humans,Liver Neoplasms,Neoplasm Metastasis,Prognosis,RNA Splicing Factors,RNA-Binding Proteins,Tumor Cells Cultured}
}
@article{hubschmannMutationalMechanismsShaping2021,
title = {Mutational Mechanisms Shaping the Coding and Noncoding Genome of Germinal Center Derived {{B-cell}} Lymphomas},
author = {Hübschmann, Daniel and Kleinheinz, Kortine and Wagener, Rabea and Bernhart, Stephan H. and López, Cristina and Toprak, Umut H. and Sungalee, Stephanie and Ishaque, Naveed and Kretzmer, Helene and Kreuz, Markus and Waszak, Sebastian M. and Paramasivam, Nagarajan and Ammerpohl, Ole and Aukema, Sietse M. and Beekman, Renée and Bergmann, Anke K. and Bieg, Matthias and Binder, Hans and Borkhardt, Arndt and Borst, Christoph and Brors, Benedikt and Bruns, Philipp and Carrillo de Santa Pau, Enrique and Claviez, Alexander and Doose, Gero and Haake, Andrea and Karsch, Dennis and Haas, Siegfried and Hansmann, Martin-Leo and Hoell, Jessica I. and Hovestadt, Volker and Huang, Bingding and Hummel, Michael and Jäger-Schmidt, Christina and Kerssemakers, Jules N. A. and Korbel, Jan O. and Kube, Dieter and Lawerenz, Chris and Lenze, Dido and Martens, Joost H. A. and Ott, German and Radlwimmer, Bernhard and Reisinger, Eva and Richter, Julia and Rico, Daniel and Rosenstiel, Philip and Rosenwald, Andreas and Schillhabel, Markus and Stilgenbauer, Stephan and Stadler, Peter F. and Martín-Subero, José I. and Szczepanowski, Monika and Warsow, Gregor and Weniger, Marc A. and Zapatka, Marc and Valencia, Alfonso and Stunnenberg, Hendrik G. and Lichter, Peter and Möller, Peter and Loeffler, Markus and Eils, Roland and Klapper, Wolfram and Hoffmann, Steve and Trümper, Lorenz and {ICGC MMML-Seq consortium} and {ICGC DE-Mining consortium} and {BLUEPRINT consortium} and Küppers, Ralf and Schlesner, Matthias and Siebert, Reiner},
date = {2021-07},
journaltitle = {Leukemia},
shortjournal = {Leukemia},
volume = {35},
number = {7},
eprint = {33953289},
eprinttype = {pmid},
pages = {2002--2016},
issn = {1476-5551},
doi = {10.1038/s41375-021-01251-z},
abstract = {B cells have the unique property to somatically alter their immunoglobulin (IG) genes by V(D)J recombination, somatic hypermutation (SHM) and class-switch recombination (CSR). Aberrant targeting of these mechanisms is implicated in lymphomagenesis, but the mutational processes are poorly understood. By performing whole genome and transcriptome sequencing of 181 germinal center derived B-cell lymphomas (gcBCL) we identified distinct mutational signatures linked to SHM and CSR. We show that not only SHM, but presumably also CSR causes off-target mutations in non-IG genes. Kataegis clusters with high mutational density mainly affected early replicating regions and were enriched for SHM- and CSR-mediated off-target mutations. Moreover, they often co-occurred in loci physically interacting in the nucleus, suggesting that mutation hotspots promote increased mutation targeting of spatially co-localized loci (termed hypermutation by proxy). Only around 1\% of somatic small variants were in protein coding sequences, but in about half of the driver genes, a contribution of B-cell specific mutational processes to their mutations was found. The B-cell-specific mutational processes contribute to both lymphoma initiation and intratumoral heterogeneity. Overall, we demonstrate that mutational processes involved in the development of gcBCL are more complex than previously appreciated, and that B cell-specific mutational processes contribute via diverse mechanisms to lymphomagenesis.},
langid = {english},
pmcid = {PMC8257491},
keywords = {Adult,B-Lymphocytes,Cell Line,Cell Line Tumor,Genes Immunoglobulin,Genome,Germinal Center,HeLa Cells,Hep G2 Cells,Human Umbilical Vein Endothelial Cells,Humans,Immunoglobulin Class Switching,K562 Cells,Lymphoma B-Cell,MCF-7 Cells,Mutation,Somatic Hypermutation Immunoglobulin,V(D)J Recombination}
}
@article{hwangPhosphorylationPolyRC2017,
title = {Phosphorylation of Poly({{rC}}) Binding Protein 1 ({{PCBP1}}) Contributes to Stabilization of Mu Opioid Receptor ({{MOR}}) {{mRNA}} via Interaction with {{AU-rich}} Element {{RNA-binding}} Protein 1 ({{AUF1}}) and Poly {{A}} Binding Protein ({{PABP}})},
author = {Hwang, Cheol Kyu and Wagley, Yadav and Law, Ping-Yee and Wei, Li-Na and Loh, Horace H.},
date = {2017-01-20},
journaltitle = {Gene},
shortjournal = {Gene},
volume = {598},
eprint = {27836661},
eprinttype = {pmid},
pages = {113--130},
issn = {1879-0038},
doi = {10.1016/j.gene.2016.11.003},
abstract = {Gene regulation at the post-transcriptional level is frequently based on cis- and trans-acting factors on target mRNAs. We found a C-rich element (CRE) in mu-opioid receptor (MOR) 3'-untranslated region (UTR) to which poly (rC) binding protein 1 (PCBP1) binds, resulting in MOR mRNA stabilization. RNA immunoprecipitation and RNA EMSA revealed the formation of PCBP1-RNA complexes at the element. Knockdown of PCBP1 decreased MOR mRNA half-life and protein expression. Stimulation by forskolin increased cytoplasmic localization of PCBP1 and PCBP1/MOR 3'-UTR interactions via increased serine phosphorylation that was blocked by protein kinase A (PKA) or (phosphatidyl inositol-3) PI3-kinase inhibitors. The forskolin treatment also enhanced serine- and tyrosine-phosphorylation of AU-rich element binding protein (AUF1), concurrent with its increased binding to the CRE, and led to an increased interaction of poly A binding protein (PABP) with the CRE and poly(A) sites. AUF1 phosphorylation also led to an increased interaction with PCBP1. These findings suggest that a single co-regulator, PCBP1, plays a crucial role in stabilizing MOR mRNA, and is induced by PKA signaling by conforming to AUF1 and PABP.},
langid = {english},
pmcid = {PMC5214663},
keywords = {3' Untranslated Regions,3′-Untranslated region,Binding Sites,Cell Line Tumor,Colforsin,DNA-Binding Proteins,Gene Knockdown Techniques,Heterogeneous Nuclear Ribonucleoprotein D0,Heterogeneous-Nuclear Ribonucleoprotein D,Heterogeneous-Nuclear Ribonucleoproteins,Humans,Models Biological,Mu opioid receptor,Phosphorylation,Poly(A)-Binding Proteins,Protein kinase A signaling,Receptors Opioid mu,RNA binding protein,RNA Messenger,RNA Processing Post-Transcriptional,RNA stability,RNA Stability,RNA-Binding Proteins,Up-Regulation}
}
@article{ishiiSpecificBindingPCBP12018,
title = {Specific Binding of {{PCBP1}} to Heavily Oxidized {{RNA}} to Induce Cell Death},
author = {Ishii, Takashi and Hayakawa, Hiroshi and Igawa, Tatsuhiro and Sekiguchi, Takeshi and Sekiguchi, Mutsuo},
date = {2018-06-26},
journaltitle = {Proceedings of the National Academy of Sciences of the United States of America},
shortjournal = {Proc Natl Acad Sci U S A},
volume = {115},
number = {26},
eprint = {29891675},
eprinttype = {pmid},
pages = {6715--6720},
issn = {0027-8424},
doi = {10.1073/pnas.1806912115},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6042155/},
urldate = {2022-09-28},
abstract = {The binding of human PCBP1 protein to heavily oxidized RNA triggers the induction of apoptosis-related reactions, including the activation of caspase-3 and the cleavage of PARP-1. The introduction of amino acid substitutions in the PCBP1 abolishes this, resulting in the failure of PARP-1 cleavage. Human cells appear to possess a mechanism to induce cell death when their messenger RNAs are severely damaged. This mechanism might be related to the accumulation of abnormal proteins in long-lived cells, such as those in the nervous system., In aerobically growing cells, the guanine base of RNA is oxidized to 8-oxo-7,8-dihydroguanine (8-oxoG), which induces alteration in their gene expression. We previously demonstrated that the human AUF1 protein binds to 8-oxoG in RNA to induce the selective degradation of oxidized messenger RNA. We herein report that the poly(C)-binding protein PCBP1 binds to more severely oxidized RNA to activate apoptosis-related reactions. While AUF1 binds to oligoribonucleotides carrying a single 8-oxoG, PCBP1 does not bind to such oligoribonucleotides but instead binds firmly to oligoribonucleotides in which two 8-oxoG residues are located nearby. PCBP1-deficient cells, constructed from the human HeLa S3 line using the CRISPR-Cas9 system, exhibited higher survival rates than HeLa S3 cells when small doses of hydrogen peroxide were applied. The levels of caspase-3 activation and PARP-1 cleavage in the PCBP1-deficient cells were significantly lower than those in wild-type cells. The structure–function relationship of PCBP1 was established with the use of PCBP1 mutant proteins in which the conserved KH domains were defective. Human cells appear to possess two distinct mechanisms, one controlled by AUF1 and the other by PCBP1, with the former functioning when messenger RNA is moderately oxidized and the latter operating when the RNA is more severely damaged.},
pmcid = {PMC6042155}
}
@article{jalladesExomeSequencingIdentifies2017,
title = {Exome Sequencing Identifies Recurrent {{BCOR}} Alterations and the Absence of {{KLF2}}, {{TNFAIP3}} and {{MYD88}} Mutations in Splenic Diffuse Red Pulp Small {{B-cell}} Lymphoma},
author = {Jallades, Laurent and Baseggio, Lucile and Sujobert, Pierre and Huet, Sarah and Chabane, Kaddour and Callet-Bauchu, Evelyne and Verney, Aurélie and Hayette, Sandrine and Desvignes, Jean-Pierre and Salgado, David and Levy, Nicolas and Béroud, Christophe and Felman, Pascale and Berger, Françoise and Magaud, Jean-Pierre and Genestier, Laurent and Salles, Gilles and Traverse-Glehen, Alexandra},
date = {2017-10},
journaltitle = {Haematologica},
shortjournal = {Haematologica},
volume = {102},
number = {10},
eprint = {28751561},
eprinttype = {pmid},
pages = {1758--1766},
issn = {1592-8721},
doi = {10.3324/haematol.2016.160192},
abstract = {Splenic diffuse red pulp lymphoma is an indolent small B-cell lymphoma recognized as a provisional entity in the World Health Organization 2008 classification. Its precise relationship to other related splenic B-cell lymphomas with frequent leukemic involvement or other lymphoproliferative disorders remains undetermined. We performed whole-exome sequencing to explore the genetic landscape of ten cases of splenic diffuse red pulp lymphoma using paired tumor and normal samples. A selection of 109 somatic mutations was then evaluated in a cohort including 42 samples of splenic diffuse red pulp lymphoma and compared to those identified in 46 samples of splenic marginal zone lymphoma and eight samples of hairy-cell leukemia. Recurrent mutations or losses in BCOR (the gene encoding the BCL6 corepressor) - frameshift (n=3), nonsense (n=2), splicing site (n=1), and copy number loss (n=4) - were identified in 10/42 samples of splenic diffuse red pulp lymphoma (24\%), whereas only one frameshift mutation was identified in 46 cases of splenic marginal zone lymphoma (2\%). Inversely, KLF2, TNFAIP3 and MYD88, common mutations in splenic marginal zone lymphoma, were rare (one KLF2 mutant in 42 samples; 2\%) or absent (TNFAIP3 and MYD88) in splenic diffuse red pulp lymphoma. These findings define an original genetic profile of splenic diffuse red pulp lymphoma and suggest that the mechanisms of pathogenesis of this lymphoma are distinct from those of splenic marginal zone lymphoma and hairy-cell leukemia.},
langid = {english},
pmcid = {PMC5622860},
keywords = {Aged,Aged 80 and over,Biomarkers Tumor,Chromosome Aberrations,DNA Copy Number Variations,Exome Sequencing,Female,Genetic Variation,Humans,Kruppel-Like Transcription Factors,Leukemia Hairy Cell,Lymphoma B-Cell,Lymphoma B-Cell Marginal Zone,Middle Aged,Mutation,Myeloid Differentiation Factor 88,Proto-Oncogene Proteins,Repressor Proteins,Splenic Neoplasms,Tumor Necrosis Factor alpha-Induced Protein 3}
}
@article{jardinRecurrentMutationsExportin2016,
title = {Recurrent Mutations of the Exportin 1 Gene ({{XPO1}}) and Their Impact on Selective Inhibitor of Nuclear Export Compounds Sensitivity in Primary Mediastinal {{B-cell}} Lymphoma},
author = {Jardin, Fabrice and Pujals, Anais and Pelletier, Laura and Bohers, Elodie and Camus, Vincent and Mareschal, Sylvain and Dubois, Sydney and Sola, Brigitte and Ochmann, Marlène and Lemonnier, François and Viailly, Pierre-Julien and Bertrand, Philippe and Maingonnat, Catherine and Traverse-Glehen, Alexandra and Gaulard, Philippe and Damotte, Diane and Delarue, Richard and Haioun, Corinne and Argueta, Christian and Landesman, Yosef and Salles, Gilles and Jais, Jean-Philippe and Figeac, Martin and Copie-Bergman, Christiane and Molina, Thierry Jo and Picquenot, Jean Michel and Cornic, Marie and Fest, Thierry and Milpied, Noel and Lemasle, Emilie and Stamatoullas, Aspasia and Moeller, Peter and Dyer, Martin J. S. and Sundstrom, Christer and Bastard, Christian and Tilly, Hervé and Leroy, Karen},
date = {2016-09},
journaltitle = {American Journal of Hematology},
shortjournal = {Am J Hematol},
volume = {91},
number = {9},
eprint = {27312795},
eprinttype = {pmid},
pages = {923--930},
issn = {1096-8652},
doi = {10.1002/ajh.24451},
abstract = {Primary mediastinal B-cell lymphoma (PMBL) is an entity of B-cell lymphoma distinct from the other molecular subtypes of diffuse large B-cell lymphoma (DLBCL). We investigated the prevalence, specificity, and clinical relevance of mutations of XPO1, which encodes a member of the karyopherin-β nuclear transporters, in a large cohort of PMBL. PMBL cases defined histologically or by gene expression profiling (GEP) were sequenced and the XPO1 mutational status was correlated to genetic and clinical characteristics. The XPO1 mutational status was also assessed in DLBCL, Hodgkin lymphoma (HL) and mediastinal gray-zone lymphoma (MGZL).The biological impact of the mutation on Selective Inhibitor of Nuclear Export (SINE) compounds (KPT-185/330) sensitivity was investigated in vitro. XPO1 mutations were present in 28/117 (24\%) PMBL cases and in 5/19 (26\%) HL cases but absent/rare in MGZL (0/20) or DLBCL (3/197). A higher prevalence (50\%) of the recurrent codon 571 variant (p.E571K) was observed in GEP-defined PMBL and was associated with shorter PFS. Age, International Prognostic Index and bulky mass were similar in XPO1 mutant and wild-type cases. KPT-185 induced a dose-dependent decrease in cell proliferation and increased cell-death in PMBL cell lines harboring wild type or XPO1 E571K mutant alleles. Experiments in transfected U2OS cells further confirmed that the XPO1 E571K mutation does not have a drastic impact on KPT-330 binding. To conclude the XPO1 E571K mutation represents a genetic hallmark of the PMBL subtype and serves as a new relevant PMBL biomarker. SINE compounds appear active for both mutated and wild-type protein. Am. J. Hematol. 91:923-930, 2016. © 2016 Wiley Periodicals, Inc.},
langid = {english},
keywords = {Acrylates,Active Transport Cell Nucleus,Adolescent,Adult,Aged,Biomarkers,Cell Line Tumor,Exportin 1 Protein,Female,Gene Expression Profiling,Hodgkin Disease,Humans,Hydrazines,Karyopherins,Lymphoma B-Cell,Male,Mediastinal Neoplasms,Middle Aged,Mutation,Receptors Cytoplasmic and Nuclear,Sequence Analysis DNA,Triazoles,Young Adult}
}
@article{johnsonDiffuseLargeBcell2009,
title = {Diffuse Large {{B-cell}} Lymphoma: Reduced {{CD20}} Expression Is Associated with an Inferior Survival},
author = {Johnson, N A and Boyle, M and Bashashati, A and Leach, S and Brooks-Wilson, A and Sehn, L H and Chhanabhai, M and Brinkman, R R and Connors, J M and Weng, A P and Gascoyne, R D},
date = {2009-04},
journaltitle = {Blood},
volume = {113},
number = {16},
pages = {3773--3780}
}
@article{johnstonCmycHypermutationBurkitt1992,
title = {C-Myc Hypermutation in {{Burkitt}}'s Lymphoma},
author = {Johnston, J. M. and Carroll, W. L.},
date = {1992-12},
journaltitle = {Leukemia \& Lymphoma},
shortjournal = {Leuk Lymphoma},
volume = {8},
number = {6},
eprint = {1297477},
eprinttype = {pmid},
pages = {431--439},
issn = {1042-8194},
doi = {10.3109/10428199209051025},
abstract = {Translocation between the c-myc protooncogene and one of the three immunoglobulin loci is a cytogenetic hallmark of the B cell tumor, Burkitt's lymphoma. The resulting deregulation of c-myc expression is a critical step in tumorigenesis. The translocation breakpoint may lie within c-myc proper, in which case deregulation is due, in part, to dissociation of key 5' regulatory sequences from the protein-coding portions of the gene. Alternatively, the breakpoint may flank c-myc, leaving the gene grossly intact. In these latter cases, mutation, which may be extensive, is usually seen within c-myc, specifically at or near the same key regulatory sequences. The precise contribution of these mutations to c-myc deregulation is gradually being clarified. The mechanisms underlying c-myc mutations are not known. Hypermutation in c-myc may reflect the influence of the juxtaposed immunoglobulin gene, which is subject to hypermutation during an intermediate stage of normal B lymphoid development. This relationship, however, has not been firmly established.},
langid = {english},
keywords = {B-Lymphocytes,Burkitt Lymphoma,Gene Expression Regulation Neoplastic,Genes Immunoglobulin,Genes myc,Humans,Mutation,Transcription Genetic}
}
@article{jumaaSplicingFactorSRp201997,
title = {The Splicing Factor {{SRp20}} Modifies Splicing of Its Own {{mRNA}} and {{ASF}}/{{SF2}} Antagonizes This Regulation},
author = {Jumaa, H. and Nielsen, P. J.},
date = {1997-08-15},
journaltitle = {The EMBO journal},
shortjournal = {EMBO J.},
volume = {16},
number = {16},
eprint = {9305649},
eprinttype = {pmid},
pages = {5077--5085},
issn = {0261-4189},
doi = {10.1093/emboj/16.16.5077},
abstract = {SRp20 is a member of the highly conserved SR family of splicing regulators. Using a variety of reporter gene constructs, we show that SRp20 regulates alternative splicing of its own mRNA. Overexpression of SRp20 results in a reduction in the level of exon 4-skipped SRp20 transcripts and activates the production of transcripts containing exon 4. These exon 4-included transcripts encode a truncated protein lacking the C-terminal RS domain. We provide evidence that SRp20 probably enhances the recognition of the otherwise unused, weak splice acceptor of exon 4. The recognition of exons with weak splice acceptor sites may be a general activity of SRp20. Unexpectedly, ASF/SF2, another member of the SR family, antagonizes the effect of SRp20 on SRp20 pre-mRNA splicing and suppresses the production of the exon 4-included form. Our results indicate that ASF/SF2 suppresses the use of the alternative exon 4, most likely by inhibiting the recognition of the splice donor of exon 4. These results demonstrate, for the first time, an auto-regulatory activity of an SR protein which is antagonized by a second SR protein.},
langid = {english},
pmcid = {PMC1170142},
keywords = {Alternative Splicing,Animals,Base Sequence,Blotting Northern,Blotting Western,Cloning Molecular,Exons,Gene Expression Regulation,Genes Reporter,Genetic Vectors,Mice,Molecular Sequence Data,Mutagenesis Site-Directed,Nuclear Proteins,Promoter Regions Genetic,RNA Messenger,RNA Precursors,RNA-Binding Proteins,Sequence Analysis DNA,Serine-Arginine Splicing Factors,Spliceosomes,Transfection,Tumor Cells Cultured}
}
@article{juszczynskiBCL6ModulatesTonic2009,
title = {{{BCL6}} Modulates Tonic {{BCR}} Signaling in Diffuse Large {{B-cell}} Lymphomas by Repressing the {{SYK}} Phosphatase, {{PTPROt}}.},
author = {Juszczynski, Przemyslaw and Chen, Linfeng and O'Donnell, Evan and Polo, Jose M and Ranuncolo, Stella M and Dalla-Favera, Riccardo and Melnick, Ari and Shipp, Margaret A},
date = {2009-12},
journaltitle = {Blood},
volume = {114},
number = {26},
pages = {5315--5321}
}
@article{kalmbachNovelInsightsPathogenesis2023,
title = {Novel Insights into the Pathogenesis of Follicular Lymphoma by Molecular Profiling of Localized and Systemic Disease Forms},
author = {Kalmbach, Sabrina and Grau, Michael and Zapukhlyak, Myroslav and Leich, Ellen and Jurinovic, Vindi and Hoster, Eva and Staiger, Annette M. and Kurz, Katrin S. and Weigert, Oliver and Gaitzsch, Erik and Passerini, Verena and Engelhard, Marianne and Herfarth, Klaus and Beiske, Klaus and Micci, Francesca and Möller, Peter and Bernd, Heinz-Wolfram and Feller, Alfred C. and Klapper, Wolfram and Stein, Harald and Hansmann, Martin-Leo and Hartmann, Sylvia and Dreyling, Martin and Holte, Harald and Lenz, Georg and Rosenwald, Andreas and Ott, German and Horn, Heike and {German Lymphoma Alliance (GLA)}},
date = {2023-10},
journaltitle = {Leukemia},
shortjournal = {Leukemia},
volume = {37},
number = {10},
eprint = {37563306},
eprinttype = {pmid},
pages = {2058--2065},
issn = {1476-5551},
doi = {10.1038/s41375-023-01995-w},
abstract = {Knowledge on the pathogenesis of FL is mainly based on data derived from advanced/systemic stages of FL (sFL) and only small cohorts of localized FL (lFL) have been characterized intensively so far. Comprehensive analysis with profiling of somatic copy number alterations (SCNA) and whole exome sequencing (WES) was performed in 147 lFL and 122 sFL. Putative targets were analyzed for gene and protein expression. Overall, lFL and sFL, as well as BCL2 translocation-positive (BCL2+) and -negative (BCL2-) FL showed overlapping features in SCNA and mutational profiles. Significant differences between lFL and sFL, however, were detected for SCNA frequencies, e.g., in 18q-gains (14\% lFL vs. 36\% sFL; p\,=\,0.0003). Although rare in lFL, gains in 18q21 were associated with inferior progression-free survival (PFS). The mutational landscape of lFL and sFL included typical genetic lesions. However, ARID1A mutations were significantly more often detected in sFL (29\%) compared to lFL (6\%, p\,=\,0.0001). In BCL2\,+\,FL mutations in KMT2D, BCL2, ABL2, IGLL5 and ARID1A were enriched, while STAT6 mutations more frequently occurred in BCL2- FL. Although the landscape of lFL and sFL showed overlapping features, molecular profiling revealed novel insights and identified gains in 18q21 as prognostic marker in lFL.},
langid = {english},
pmcid = {PMC10539171},
keywords = {Humans,In Situ Hybridization Fluorescence,Lymphoma Follicular,Mutation,Proto-Oncogene Proteins c-bcl-2,Translocation Genetic}
}
@article{kaymazComprehensiveTranscriptomeMutational2017,
title = {Comprehensive {{Transcriptome}} and {{Mutational Profiling}} of {{Endemic Burkitt Lymphoma Reveals EBV Type}}–{{Specific Differences}}},
author = {Kaymaz, Yasin and Oduor, Cliff I. and Yu, Hongbo and Otieno, Juliana A. and Ong'echa, John Michael and Moormann, Ann M. and Bailey, Jeffrey A.},
date = {2017-05-01},
journaltitle = {Molecular Cancer Research},
shortjournal = {Molecular Cancer Research},
volume = {15},
number = {5},
pages = {563--576},
issn = {1541-7786},
doi = {10.1158/1541-7786.MCR-16-0305},
url = {https://doi.org/10.1158/1541-7786.MCR-16-0305},
urldate = {2022-05-29},
abstract = {Endemic Burkitt lymphoma (eBL) is the most common pediatric cancer in malaria-endemic equatorial Africa and nearly always contains Epstein–Barr virus (EBV), unlike sporadic Burkitt lymphoma (sBL) that occurs with a lower incidence in developed countries. Given these differences and the variable clinical presentation and outcomes, we sought to further understand pathogenesis by investigating transcriptomes using RNA sequencing (RNAseq) from multiple primary eBL tumors compared with sBL tumors. Within eBL tumors, minimal expression differences were found based on: anatomical presentation site, in-hospital survival rates, and EBV genome type, suggesting that eBL tumors are homogeneous without marked subtypes. The outstanding difference detected using surrogate variable analysis was the significantly decreased expression of key genes in the immunoproteasome complex (PSMB9/β1i, PSMB10/β2i, PSMB8/β5i, and PSME2/PA28β) in eBL tumors carrying type 2 EBV compared with type 1 EBV. Second, in comparison with previously published pediatric sBL specimens, the majority of the expression and pathway differences was related to the PTEN/PI3K/mTOR signaling pathway and was correlated most strongly with EBV status rather than geographic designation. Third, common mutations were observed significantly less frequently in eBL tumors harboring EBV type 1, with mutation frequencies similar between tumors with EBV type 2 and without EBV. In addition to the previously reported genes, a set of new genes mutated in BL, including TFAP4, MSH6, PRRC2C, BCL7A, FOXO1, PLCG2, PRKDC, RAD50, and RPRD2, were identified. Overall, these data establish that EBV, particularly EBV type 1, supports BL oncogenesis, alleviating the need for certain driver mutations in the human genome.Implications: Genomic and mutational analyses of Burkitt lymphoma tumors identify key differences based on viral content and clinical outcomes suggesting new avenues for the development of prognostic molecular biomarkers and therapeutic interventions. Mol Cancer Res; 15(5); 563–76. ©2017 AACR.}
}
@article{kendrickDiffuseLargeBcell2016,
title = {Diffuse Large {{B-cell}} Lymphoma Cell-of-Origin Classification Using the {{Lymph2Cx}} Assay in the Context of {{BCL2}} and {{MYC}} Expression Status.},
author = {Kendrick, Samantha and Tus, Katalin and Wright, George and Jaffe, Elaine S and Rosenwald, Andreas and Campo, Elias and Chan, Wing-Chung and Connors, Joseph M and Braziel, Rita M and Ott, German and Delabie, Jan and Cook, James R and Weisenburger, Dennis D and Greiner, Timothy C and Fu, Kai and Staudt, Louis M and Gascoyne, Randy D and Scott, David W and Rimsza, Lisa M},
date = {2016},
journaltitle = {Leuk lymphoma},
volume = {57},
number = {3},
pages = {717--720}
}
@article{khanHnRNPHnRNPH12021,
title = {{{HnRNP F}} and {{hnRNP H1}} Regulate {{mRNA}} Stability of Amyloid Precursor Protein},
author = {Khan, Muhammad I. and Zhang, Juan and Liu, Qiang},
date = {2021-06-09},
journaltitle = {Neuroreport},
shortjournal = {Neuroreport},
volume = {32},
number = {9},
eprint = {33994531},
eprinttype = {pmid},
pages = {824--832},
issn = {1473-558X},
doi = {10.1097/WNR.0000000000001662},
abstract = {Amyloid precursor protein (APP) is a transmembrane protein that plays a crucial role in the production of amyloid-β peptides. Any disruption in APP protein production, its mRNA decay rate or processing may result in abnormal production of amyloid-β peptides and subsequent development of protein aggregation diseases. Therefore, the equilibrium is crucial for neuronal function. An association study of heterogeneous nuclear ribonucleoprotein (hnRNP)-F and hnRNP H1 with APP was carried out in Neuro-2a (N2a) cells. In the present study, we found that hnRNP F and hnRNP H1 were significantly upregulated in the hippocampus of APP/PS1 mice. The changes in APP expression were positively associated with hnRNP F and hnRNP H1 when hnRNP F and hnRNP H1 were depleted or increased in N2a cells. Importantly, cross-linked RNA immunoprecipitation demonstrated binding affinities of hnRNP F and hnRNP H1 for App mRNA. Mechanistically, mRNA stability assay revealed that overexpression of hnRNP F or hnRNP H1 increases the APP level by stabilizing App mRNA half-life, implying that levels of hnRNP F and hnRNP H1 can change the production of APP. Further understanding of the regulatory mechanism of APP expression in association with hnRNP F and hnRNP H1 would provide insights into the mechanism underlying the maintenance of brain health and cognition. This study provides a theoretical basis for the development of hnRNP-stabilizing compounds to regulate APP.},
langid = {english},
keywords = {Alzheimer Disease,Amyloid beta-Protein Precursor,Animals,Cell Line Tumor,Gene Expression Regulation,Heterogeneous-Nuclear Ribonucleoprotein Group F-H,Hippocampus,Mice,Mice Transgenic,RNA Messenger,RNA Stability}
}
@article{kharelPropertiesBiologicalImpact2020,
title = {Properties and Biological Impact of {{RNA G-quadruplexes}}: From Order to Turmoil and Back},
shorttitle = {Properties and Biological Impact of {{RNA G-quadruplexes}}},
author = {Kharel, Prakash and Becker, Gertraud and Tsvetkov, Vladimir and Ivanov, Pavel},
date = {2020-12-16},
journaltitle = {Nucleic Acids Research},
shortjournal = {Nucleic Acids Research},
volume = {48},
number = {22},
pages = {12534--12555},
issn = {0305-1048},
doi = {10.1093/nar/gkaa1126},
url = {https://doi.org/10.1093/nar/gkaa1126},
urldate = {2022-10-15},
abstract = {Guanine-quadruplexes (G4s) are non-canonical four-stranded structures that can be formed in guanine (G) rich nucleic acid sequences. A great number of G-rich sequences capable of forming G4 structures have been described based on in vitro analysis, and evidence supporting their formation in live cells continues to accumulate. While formation of DNA G4s (dG4s) within chromatin in vivo has been supported by different chemical, imaging and genomic approaches, formation of RNA G4s (rG4s) in vivo remains a matter of discussion. Recent data support the dynamic nature of G4 formation in the transcriptome. Such dynamic fluctuation of rG4 folding-unfolding underpins the biological significance of these structures in the regulation of RNA metabolism. Moreover, rG4-mediated functions may ultimately be connected to mechanisms underlying disease pathologies and, potentially, provide novel options for therapeutics. In this framework, we will review the landscape of rG4s within the transcriptome, focus on their potential impact on biological processes, and consider an emerging connection of these functions in human health and disease.}
}
@article{khodabakhshiRecurrentTargetsAberrant2012,
title = {Recurrent Targets of Aberrant Somatic Hypermutation in Lymphoma},
author = {Khodabakhshi, Alireza Hadj and Morin, Ryan D. and Fejes, Anthony P. and Mungall, Andrew J. and Mungall, Karen L. and Bolger-Munro, Madison and Johnson, Nathalie A. and Connors, Joseph M. and Gascoyne, Randy D. and Marra, Marco A. and Birol, Inanc and Jones, Steven J. M.},
year = {2012},
journaltitle = {Oncotarget},
shortjournal = {Oncotarget},
volume = {3},
number = {11},
eprint = {23131835},
eprinttype = {pmid},
pages = {1308--1319},
issn = {1949-2553},
abstract = {Somatic hypermutation (SHM) in the variable region of immunoglobulin genes (IGV) naturally occurs in a narrow window of B cell development to provide high-affinity antibodies. However, SHM can also aberrantly target proto-oncogenes and cause genome instability. The role of aberrant SHM (aSHM) has been widely studied in various non-Hodgkin's lymphoma particularly in diffuse large B-cell lymphoma (DLBCL). Although, it has been speculated that aSHM targets a wide range of genome loci so far only twelve genes have been identified as targets of aSHM through the targeted sequencing of selected genes. A genome-wide study aiming at identifying a comprehensive set of aSHM targets recurrently occurring in DLBCL has not been previously undertaken. Here, we present a comprehensive assessment of the somatic hypermutated genes in DLBCL identified through an analysis of genomic and transcriptome data derived from 40 DLBCL patients. Our analysis verifies that there are indeed many genes that are recurrently affected by aSHM. In particular, we have identified 32 novel targets that show same or higher level of aSHM activity than genes previously reported. Amongst these novel targets, 22 genes showed a significant correlation between mRNA abundance and aSHM.},
pmcid = {PMC3717795}
}
@article{khodadoustAntigenPresentationProfiling2017,
title = {Antigen Presentation Profiling Reveals Recognition of Lymphoma Immunoglobulin Neoantigens},
author = {Khodadoust, Michael S. and Olsson, Niclas and Wagar, Lisa E. and Haabeth, Ole A. W. and Chen, Binbin and Swaminathan, Kavya and Rawson, Keith and Liu, Chih Long and Steiner, David and Lund, Peder and Rao, Samhita and Zhang, Lichao and Marceau, Caleb and Stehr, Henning and Newman, Aaron M. and Czerwinski, Debra K. and Carlton, Victoria E. H. and Moorhead, Martin and Faham, Malek and Kohrt, Holbrook E. and Carette, Jan and Green, Michael R. and Davis, Mark M. and Levy, Ronald and Elias, Joshua E. and Alizadeh, Ash A.},
date = {2017-03},
journaltitle = {Nature},
volume = {543},
number = {7647},
pages = {723--727},
issn = {1476-4687},
doi = {10.1038/nature21433},
url = {https://www.nature.com/articles/nature21433},
urldate = {2019-12-21},
abstract = {Evidence for the abundant presentation of class II neoantigens by a human B-cell lymphoma.},
langid = {english}
}
@article{kimCD79BMYD88Mutations2014,
title = {{{CD79B}} and {{MYD88}} Mutations in Diffuse Large {{B-cell}} Lymphoma.},
author = {Kim, Yuil and Ju, Hyunjeong and Kim, Dong Hoon and Yoo, Hae Yong and Kim, Suk Jin and Kim, Won Seog and Ko, Young-Hyeh},
date = {2014-03},
journaltitle = {Hum Pathol},
volume = {45},
number = {3},
pages = {556--564}
}
@article{kimHnRNPMediatesPhasedependent2011,
title = {{{hnRNP Q}} Mediates a Phase-Dependent Translation-Coupled {{mRNA}} Decay of Mouse {{Period3}}},
author = {Kim, Do-Yeon and Kwak, Eunyee and Kim, Sung-Hoon and Lee, Kyung-Ha and Woo, Kyung-Chul and Kim, Kyong-Tai},
date = {2011-11-01},
journaltitle = {Nucleic Acids Research},
shortjournal = {Nucleic Acids Research},
volume = {39},
number = {20},
pages = {8901--8914},
issn = {0305-1048},
doi = {10.1093/nar/gkr605},
url = {https://doi.org/10.1093/nar/gkr605},
urldate = {2022-09-28},
abstract = {Daily mRNA oscillations of circadian clock genes largely depend on transcriptional regulation. However, several lines of evidence highlight the critical role of post-transcriptional regulation in the oscillations of circadian mRNA oscillations. Clearly, variations in the mRNA decay rate lead to changes in the cycling profiles. However, the mechanisms controlling the mRNA stability of clock genes are not fully understood. Here we demonstrate that the turnover rate of mouse Period3 (m Per3 ) mRNA is dramatically changed in a circadian phase-dependent manner. Furthermore, the circadian regulation of m Per3 mRNA stability requires the cooperative function of 5′- and 3′-untranslated regions (UTRs). Heterogeneous nuclear ribonucleoprotein Q (hnRNP Q) binds to both 5′- and 3′-UTR and triggers enhancement of translation and acceleration of mRNA decay. We propose the phase-dependent translation coupled mRNA decay mediated by hnRNP Q as a new regulatory mechanism of the rhythmically regulated decay of m Per3 mRNA.}
}
@article{kimmelmanFaithfulCompanionsProposal2007,
title = {Faithful Companions: A Proposal for Neurooncology Trials in Pet Dogs},
shorttitle = {Faithful Companions},
author = {Kimmelman, Jonathan and Nalbantoglu, Josephine},
date = {2007-05-15},
journaltitle = {Cancer Research},
shortjournal = {Cancer Res},
volume = {67},
number = {10},
eprint = {17510377},
eprinttype = {pmid},
pages = {4541--4544},
issn = {0008-5472},
doi = {10.1158/0008-5472.CAN-06-3792},
abstract = {Although relatively rare, malignant glioma (MG) is frequently used for testing novel cancer treatments. However, human MG trials have often been initiated on the basis of preclinical models that involve numerous discontinuities with the human disease. Below, we discuss various limitations of the mainstay model used in MG preclinical research, the murine orthotopic xenograft. After discussing alternative model systems like transgenic mouse models and canine xenografts, we argue that companion animals with spontaneous brain cancers offer a scientifically and ethically attractive system for preclinical testing of novel MG interventions. Ethical advantages and practical challenges of companion animal brain cancer trials are briefly discussed.},
langid = {english},
keywords = {Animal Welfare,Animals,Animals Domestic,Brain Neoplasms,Clinical Trials as Topic,Disease Models Animal,Dogs,Glioma,Humans,Mice,Mice Transgenic,Xenograft Model Antitumor Assays}
}
@report{kimStrelka2FastAccurate2017,
type = {preprint},
title = {Strelka2: {{Fast}} and Accurate Variant Calling for Clinical Sequencing Applications},
shorttitle = {Strelka2},
author = {Kim, Sangtae and Scheffler, Konrad and Halpern, Aaron L and Bekritsky, Mitchell A and Noh, Eunho and Källberg, Morten and Chen, Xiaoyu and Beyter, Doruk and Krusche, Peter and Saunders, Christopher T},
date = {2017-09-23},
institution = {Bioinformatics},
doi = {10.1101/192872},
url = {http://biorxiv.org/lookup/doi/10.1101/192872},
urldate = {2020-06-01},
abstract = {We describe Strelka2 ( https://github.com/Illumina/strelka ), an open-source small variant calling method for clinical germline and somatic sequencing applications. Strelka2 introduces a novel mixture-model based estimation of indel error parameters from each sample, an efficient tiered haplotype modeling strategy and a normal sample contamination model to improve liquid tumor analysis. For both germline and somatic calling, Strelka2 substantially outperforms current leading tools on both variant calling accuracy and compute cost.},
langid = {english}
}
@article{kimStrelka2FastAccurate2018,
title = {Strelka2: Fast and Accurate Calling of Germline and Somatic Variants},
shorttitle = {Strelka2},
author = {Kim, Sangtae and Scheffler, Konrad and Halpern, Aaron L. and Bekritsky, Mitchell A. and Noh, Eunho and Källberg, Morten and Chen, Xiaoyu and Kim, Yeonbin and Beyter, Doruk and Krusche, Peter and Saunders, Christopher T.},
date = {2018-08},
journaltitle = {Nature Methods},
shortjournal = {Nat. Methods},
volume = {15},
number = {8},
eprint = {30013048},
eprinttype = {pmid},
pages = {591--594},
issn = {1548-7105},
doi = {10.1038/s41592-018-0051-x},
abstract = {We describe Strelka2 ( https://github.com/Illumina/strelka ), an open-source small-variant-calling method for research and clinical germline and somatic sequencing applications. Strelka2 introduces a novel mixture-model-based estimation of insertion/deletion error parameters from each sample, an efficient tiered haplotype-modeling strategy, and a normal sample contamination model to improve liquid tumor analysis. For both germline and somatic calling, Strelka2 substantially outperformed the current leading tools in terms of both variant-calling accuracy and computing cost.},
langid = {english},
keywords = {Databases Genetic,Genetic Variation,Germ-Line Mutation,Haplotypes,High-Throughput Nucleotide Sequencing,Humans,INDEL Mutation,Models Genetic,Neoplasms,Software,Whole Genome Sequencing}
}
@article{kingFalsenegativeRatesMYC2019,
title = {False-Negative Rates for {{MYC}} Fluorescence in Situ Hybridization Probes in {{B-cell}} Neoplasms},
author = {King, Rebecca L. and McPhail, Ellen D. and Meyer, Reid G. and Vasmatzis, George and Pearce, Kathryn and Smadbeck, James B. and Ketterling, Rhett P. and Smoley, Stephanie A. and Greipp, Patricia T. and Hoppman, Nicole L. and Peterson, Jess F. and Baughn, Linda B.},
date = {2019-06},
journaltitle = {Haematologica},
shortjournal = {Haematologica},
volume = {104},
number = {6},
eprint = {30523057},
eprinttype = {pmid},
pages = {e248-e251},
issn = {1592-8721},
doi = {10.3324/haematol.2018.207290},
langid = {english},
pmcid = {PMC6545835}
}
@article{knutsonSelectiveInhibitionEZH22014,
title = {Selective {{Inhibition}} of {{EZH2}} by {{EPZ-6438 Leads}} to {{Potent Antitumor Activity}} in {{EZH2-Mutant Non-Hodgkin Lymphoma}}},
author = {Knutson, Sarah K. and Kawano, Satoshi and Minoshima, Yukinori and Warholic, Natalie M. and Huang, Kuan-Chun and Xiao, Yonghong and Kadowaki, Tadashi and Uesugi, Mai and Kuznetsov, Galina and Kumar, Namita and Wigle, Tim J. and Klaus, Christine R. and Allain, Christina J. and Raimondi, Alejandra and Waters, Nigel J. and Smith, Jesse J. and Porter-Scott, Margaret and Chesworth, Richard and Moyer, Mikel P. and Copeland, Robert A. and Richon, Victoria M. and Uenaka, Toshimitsu and Pollock, Roy M. and Kuntz, Kevin W. and Yokoi, Akira and Keilhack, Heike},
date = {2014},
journaltitle = {Molecular Cancer Therapeutics},
volume = {13},
number = {4},
eprint = {24563539},
eprinttype = {pmid},
pages = {842--854},
issn = {1535-7163},
doi = {10.1158/1535-7163.mct-13-0773},
url = {http://dx.doi.org/10.1158/1535-7163.mct-13-0773},
abstract = {Mutations within the catalytic domain of the histone methyltransferase EZH2 have been identified in subsets of patients with non-Hodgkin lymphoma (NHL). These genetic alterations are hypothesized to confer an oncogenic dependency on EZH2 enzymatic activity in these cancers. We have previously reported the discovery of EPZ005678 and EPZ-6438, potent and selective S-adenosyl-methionine-competitive small molecule inhibitors of EZH2. Although both compounds are similar with respect to their mechanism of action and selectivity, EPZ-6438 possesses superior potency and drug-like properties, including good oral bioavailability in animals. Here, we characterize the activity of EPZ-6438 in preclinical models of NHL. EPZ-6438 selectively inhibits intracellular lysine 27 of histone H3 (H3K27) methylation in a concentration- and time-dependent manner in both EZH2 wild-type and mutant lymphoma cells. Inhibition of H3K27 trimethylation (H3K27Me3) leads to selective cell killing of human lymphoma cell lines bearing EZH2 catalytic domain point mutations. Treatment of EZH2-mutant NHL xenograft-bearing mice with EPZ-6438 causes dose-dependent tumor growth inhibition, including complete and sustained tumor regressions with correlative diminution of H3K27Me3 levels in tumors and selected normal tissues. Mice dosed orally with EPZ-6438 for 28 days remained tumor free for up to 63 days after stopping compound treatment in two EZH2-mutant xenograft models. These data confirm the dependency of EZH2-mutant NHL on EZH2 activity and portend the utility of EPZ-6438 as a potential treatment for these genetically defined cancers. Mol Cancer Ther; 13(4); 842–54. ©2014 AACR.}
}
@article{kridelHistologicalTransformationProgression2016,
title = {Histological {{Transformation}} and {{Progression}} in {{Follicular Lymphoma}}: {{A Clonal Evolution Study}}},
shorttitle = {Histological {{Transformation}} and {{Progression}} in {{Follicular Lymphoma}}},
author = {Kridel, Robert and Chan, Fong Chun and Mottok, Anja and Boyle, Merrill and Farinha, Pedro and Tan, King and Meissner, Barbara and Bashashati, Ali and McPherson, Andrew and Roth, Andrew and Shumansky, Karey and Yap, Damian and Ben-Neriah, Susana and Rosner, Jamie and Smith, Maia A. and Nielsen, Cydney and Giné, Eva and Telenius, Adele and Ennishi, Daisuke and Mungall, Andrew and Moore, Richard and Morin, Ryan D. and Johnson, Nathalie A. and Sehn, Laurie H. and Tousseyn, Thomas and Dogan, Ahmet and Connors, Joseph M. and Scott, David W. and Steidl, Christian and Marra, Marco A. and Gascoyne, Randy D. and Shah, Sohrab P.},
date = {2016-12},
journaltitle = {PLoS medicine},
shortjournal = {PLoS Med},
volume = {13},
number = {12},
eprint = {27959929},
eprinttype = {pmid},
pages = {e1002197},
issn = {1549-1676},
doi = {10.1371/journal.pmed.1002197},
abstract = {BACKGROUND: Follicular lymphoma (FL) is an indolent, yet incurable B cell malignancy. A subset of patients experience an increased mortality rate driven by two distinct clinical end points: histological transformation and early progression after immunochemotherapy. The nature of tumor clonal dynamics leading to these clinical end points is poorly understood, and previously determined genetic alterations do not explain the majority of transformed cases or accurately predict early progressive disease. We contend that detailed knowledge of the expansion patterns of specific cell populations plus their associated mutations would provide insight into therapeutic strategies and disease biology over the time course of FL clinical histories. METHODS AND FINDINGS: Using a combination of whole genome sequencing, targeted deep sequencing, and digital droplet PCR on matched diagnostic and relapse specimens, we deciphered the constituent clonal populations in 15 transformation cases and 6 progression cases, and measured the change in clonal population abundance over time. We observed widely divergent patterns of clonal dynamics in transformed cases relative to progressed cases. Transformation specimens were generally composed of clones that were rare or absent in diagnostic specimens, consistent with dramatic clonal expansions that came to dominate the transformation specimens. This pattern was independent of time to transformation and treatment modality. By contrast, early progression specimens were composed of clones that were already present in the diagnostic specimens and exhibited only moderate clonal dynamics, even in the presence of immunochemotherapy. Analysis of somatic mutations impacting 94 genes was undertaken in an extension cohort consisting of 395 samples from 277 patients in order to decipher disrupted biology in the two clinical end points. We found 12 genes that were more commonly mutated in transformed samples than in the preceding FL tumors, including TP53, B2M, CCND3, GNA13, S1PR2, and P2RY8. Moreover, ten genes were more commonly mutated in diagnostic specimens of patients with early progression, including TP53, BTG1, MKI67, and XBP1. CONCLUSIONS: Our results illuminate contrasting modes of evolution shaping the clinical histories of transformation and progression. They have implications for interpretation of evolutionary dynamics in the context of treatment-induced selective pressures, and indicate that transformation and progression will require different clinical management strategies.},
langid = {english},
pmcid = {PMC5154502},
keywords = {Clonal Evolution,Clone Cells,Disease Progression,Humans,Lymphoma Follicular,Mutation}
}
@article{kridelWholeTranscriptomeSequencing2012,
title = {Whole Transcriptome Sequencing Reveals Recurrent {{NOTCH1}} Mutations in Mantle Cell Lymphoma},
author = {Kridel, Robert and Meissner, Barbara and Rogic, Sanja and Boyle, Merrill and Telenius, Adele and Woolcock, Bruce and Gunawardana, Jay and Jenkins, Christopher and Cochrane, Chris and Ben-Neriah, Susana and Tan, King and Morin, Ryan D. and Opat, Stephen and Sehn, Laurie H. and Connors, Joseph M. and Marra, Marco A. and Weng, Andrew P. and Steidl, Christian and Gascoyne, Randy D.},
date = {2012-03-01},
journaltitle = {Blood},
shortjournal = {Blood},
volume = {119},
number = {9},
eprint = {22210878},
eprinttype = {pmid},
pages = {1963--1971},
issn = {1528-0020},
doi = {10.1182/blood-2011-11-391474},
abstract = {Mantle cell lymphoma (MCL), an aggressive subtype of non-Hodgkin lymphoma, is characterized by the hallmark translocation t(11;14)(q13;q32) and the resulting overexpression of cyclin D1 (CCND1). Our current knowledge of this disease encompasses frequent secondary cytogenetic aberrations and the recurrent mutation of a handful of genes, such as TP53, ATM, and CCND1. However, these findings insufficiently explain the biologic underpinnings of MCL. Here, we performed whole transcriptome sequencing on a discovery cohort of 18 primary tissue MCL samples and 2 cell lines. We found recurrent mutations in NOTCH1, a finding that we confirmed in an extension cohort of 108 clinical samples and 8 cell lines. In total, 12\% of clinical samples and 20\% of cell lines harbored somatic NOTCH1 coding sequence mutations that clustered in the PEST domain and predominantly consisted of truncating mutations or small frame-shifting indels. NOTCH1 mutations were associated with poor overall survival (P = .003). Furthermore, we showed that inhibition of the NOTCH pathway reduced proliferation and induced apoptosis in 2 MCL cell lines. In summary, we have identified recurrent NOTCH1 mutations that provide the preclinical rationale for therapeutic inhibition of the NOTCH pathway in a subset of patients with MCL.},
langid = {english},
keywords = {Adult,Aged,Aged 80 and over,Amyloid Precursor Protein Secretases,Apoptosis,Base Sequence,Benzodiazepinones,Cell Line Tumor,Cell Proliferation,Cyclin D1,Exons,Female,Gene Expression Profiling,Humans,Lymphoma Mantle-Cell,Male,Middle Aged,Mutation,Prognosis,Receptor Notch1,Sequence Analysis RNA,Signal Transduction,Survival Analysis,Transcriptome}
}
@article{krysiakRecurrentSomaticMutations2017,
title = {Recurrent Somatic Mutations Affecting {{B-cell}} Receptor Signaling Pathway Genes in Follicular Lymphoma},
author = {Krysiak, Kilannin and Gomez, Felicia and White, Brian S. and Matlock, Matthew and Miller, Christopher A. and Trani, Lee and Fronick, Catrina C. and Fulton, Robert S. and Kreisel, Friederike and Cashen, Amanda F. and Carson, Kenneth R. and Berrien-Elliott, Melissa M. and Bartlett, Nancy L. and Griffith, Malachi and Griffith, Obi L. and Fehniger, Todd A.},
date = {2017-01-26},
journaltitle = {Blood},
shortjournal = {Blood},
volume = {129},
number = {4},
eprint = {28064239},
eprinttype = {pmid},
pages = {473--483},
issn = {1528-0020},
doi = {10.1182/blood-2016-07-729954},
abstract = {Follicular lymphoma (FL) is the most common form of indolent non-Hodgkin lymphoma, yet it remains only partially characterized at the genomic level. To improve our understanding of the genetic underpinnings of this incurable and clinically heterogeneous disease, whole-exome sequencing was performed on tumor/normal pairs from a discovery cohort of 24 patients with FL. Using these data and mutations identified in other B-cell malignancies, 1716 genes were sequenced in 113 FL tumor samples from 105 primarily treatment-naive individuals. We identified 39 genes that were mutated significantly above background mutation rates. CREBBP mutations were associated with inferior PFS. In contrast, mutations in previously unreported HVCN1, a voltage-gated proton channel-encoding gene and B-cell receptor signaling modulator, were associated with improved PFS. In total, 47 (44.8\%) patients harbor mutations in the interconnected B-cell receptor (BCR) and CXCR4 signaling pathways. Histone gene mutations were more frequent than previously reported (identified in 43.8\% of patients) and often co-occurred (17.1\% of patients). A novel, recurrent hotspot was identified at a posttranslationally modified residue in the histone H2B family. This study expands the number of mutated genes described in several known signaling pathways and complexes involved in lymphoma pathogenesis (BCR, Notch, SWitch/sucrose nonfermentable (SWI/SNF), vacuolar ATPases) and identified novel recurrent mutations (EGR1/2, POU2AF1, BTK, ZNF608, HVCN1) that require further investigation in the context of FL biology, prognosis, and treatment.},
langid = {english},
pmcid = {PMC5270390},
keywords = {Adult,Agammaglobulinaemia Tyrosine Kinase,Aged,Aged 80 and over,CREB-Binding Protein,Disease-Free Survival,Early Growth Response Protein 1,Female,Gene Expression Profiling,Gene Expression Regulation Neoplastic,Histones,Humans,Ion Channels,Lymphoma Follicular,Male,Middle Aged,Mutation,Protein-Tyrosine Kinases,Receptors Antigen B-Cell,Receptors CXCR4,Receptors Notch,Repressor Proteins,Signal Transduction,Trans-Activators,Vacuolar Proton-Translocating ATPases}
}
@article{kumanovicsDiffuseLargeCell2010,
title = {Diffuse Large {{B}} Cell Lymphoma in Hyper-{{IgE}} Syndrome Due to {{STAT3}} Mutation.},
author = {Kumánovics, Attila and Perkins, Sherrie L and Gilbert, Heather and Cessna, Melissa H and Augustine, Nancy H and Hill, Harry R},
date = {2010-11},
journaltitle = {Journal of clinical immunology},
volume = {30},
number = {6},
pages = {886--893}
}
@article{kwanhianMicroRNA142Mutated202012,
title = {{{MicroRNA-142}} Is Mutated in about 20\% of Diffuse Large {{B-cell}} Lymphoma},
author = {Kwanhian, Wiyada and Lenze, Dido and Alles, Julia and Motsch, Natalie and Barth, Stephanie and Döll, Celina and Imig, Jochen and Hummel, Michael and Tinguely, Marianne and Trivedi, Pankaj and Lulitanond, Viraphong and Meister, Gunter and Renner, Christoph and Grässer, Friedrich A.},
date = {2012-10},
journaltitle = {Cancer Medicine},
shortjournal = {Cancer Med},
volume = {1},
number = {2},
eprint = {23342264},
eprinttype = {pmid},
pages = {141--155},
issn = {2045-7634},
doi = {10.1002/cam4.29},
abstract = {MicroRNAs (miRNAs) are short 18-23 nucleotide long noncoding RNAs that posttranscriptionally regulate gene expression by binding to mRNA. Our previous miRNA profiling of diffuse large B-cell lymphoma (DLBCL) revealed a mutation in the seed sequence of miR-142-3p. Further analysis now showed that miR-142 was mutated in 11 (19.64\%) of the 56 DLBCL cases. Of these, one case had a mutation in both alleles, with the remainder being heterozygous. Four mutations were found in the mature miR-142-5p, four in the mature miR-142-3p, and three mutations affected the miR-142 precursor. Two mutations in the seed sequence redirected miR-142-3p to the mRNA of the transcriptional repressor ZEB2 and one of them also targeted the ZEB1 mRNA. However, the other mutations in the mature miR-142-3p did not influence either the ZEB1 or ZEB2 3' untranslated region (3' UTR). On the other hand, the mutations affecting the seed sequence of miR-142-3p resulted in a loss of responsiveness in the 3' UTR of the known miR-142-3p targets RAC1 and ADCY9. In contrast to the mouse p300 gene, the human p300 gene was not found to be a target for miR-142-5p. In one case with a mutation of the precursor, we observed aberrant processing of the miR-142-5p. Our data suggest that the mutations in miR-142 probably lead to a loss rather than a gain of function. This is the first report describing mutations of a miRNA gene in a large percentage of a distinct lymphoma subtype.},
langid = {english},
pmcid = {PMC3544448},
keywords = {Animals,Base Sequence,Carcinogenesis,Cell Line,cellular biology,E1A-Associated p300 Protein,genomics,HEK293 Cells,Homeodomain Proteins,Humans,In Situ Hybridization Fluorescence,Lymphoma Large B-Cell Diffuse,Mice,MicroRNAs,molecular genetics,Mutation,rac1 GTP-Binding Protein,Repressor Proteins,RNA Messenger,Sequence Analysis DNA,Transcription Factors,Zinc Finger E-box Binding Homeobox 2,Zinc Finger E-box-Binding Homeobox 1}
}
@article{lakeMutationsNFKBIAEncoding2009,
title = {Mutations of {{NFKBIA}}, Encoding {{IkappaB}} Alpha, Are a Recurrent Finding in Classical {{Hodgkin}} Lymphoma but Are Not a Unifying Feature of Non-{{EBV-associated}} Cases},
author = {Lake, Annette and Shield, Lesley A. and Cordano, Pablo and Chui, Daniel T. Y. and Osborne, Julie and Crae, Shauna and Wilson, Katherine S. and Tosi, Sabrina and Knight, Samantha J. L. and Gesk, Stefan and Siebert, Reiner and Hay, Ron T. and Jarrett, Ruth F.},
date = {2009-09-15},
journaltitle = {International Journal of Cancer},
shortjournal = {Int J Cancer},
volume = {125},
number = {6},
eprint = {19507254},
eprinttype = {pmid},
pages = {1334--1342},
issn = {1097-0215},
doi = {10.1002/ijc.24502},
abstract = {A consistent feature of the Hodgkin and Reed-Sternberg (HRS) cells in classical Hodgkin lymphoma (cHL) is the constitutive activation of NF-kappaB transcription factors. In Epstein-Barr virus (EBV)-associated cases of cHL, expression of viral antigens most probably leads to NF-kappaB activation but for non-EBV-associated cases, the mechanism is not clear. Previous small studies have demonstrated deleterious mutations of NFKBIA, the gene encoding IkappaB alpha, in HRS cells. In the present study, we aimed to establish the frequency of NFKBIA mutation in cHL by investigating a larger series of cases and to determine whether these mutations are a characteristic feature of non-EBV-associated cHL. Single HRS cells from 20 cases of cHL were analysed by PCRs covering all 6 exons of the gene. Clonal deleterious mutations were detected in 3 cases and in 1 case both alleles of the gene were shown to harbour mutations. NFKBIA mutations were detected only in non-EBV-associated cases but the majority of these cases had wild-type NFKBIA. It remains possible that defects in genes encoding other inhibitors of NF-kappaB, such as TNFAIP3 (A20) and CYLD, are involved in the latter cases, as described for one case in this series.},
langid = {english},
keywords = {Adolescent,Adult,Aged,Child,Comparative Genomic Hybridization,DNA-Binding Proteins,Epstein-Barr Virus Infections,Female,Gene Expression Profiling,Herpesvirus 4 Human,Hodgkin Disease,Humans,I-kappa B Proteins,Male,Middle Aged,Mutation,NF-KappaB Inhibitor alpha,Oligonucleotide Array Sequence Analysis,Polymorphism Single Nucleotide,Young Adult}
}
@article{lambertYinYangRNA2019,
title = {The {{Yin}} and {{Yang}} of {{RNA}} Surveillance in {{B}} Lymphocytes and Antibody-Secreting Plasma Cells},
author = {Lambert, Jean-Marie and Srour, Nivine and Delpy, Laurent},
date = {2019-12},
journaltitle = {BMB Reports},
shortjournal = {BMB Rep},
volume = {52},
number = {12},
eprint = {31619318},
eprinttype = {pmid},
pages = {671--678},
issn = {1976-6696},
doi = {10.5483/BMBRep.2019.52.12.232},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6941761/},
urldate = {2022-10-25},
abstract = {The random V(D)J recombination process ensures the diversity of the primary immunoglobulin (Ig) repertoire. In two thirds of cases, imprecise recombination between variable (V), diversity (D), and joining (J) segments induces a frameshift in the open reading frame that leads to the appearance of premature termination codons (PTCs). Thus, many B lineage cells harbour biallelic V(D)J-rearrangements of Ig heavy or light chain genes, with a productively-recombined allele encoding the functional Ig chain and a nonproductive allele potentially encoding truncated Ig polypeptides. Since the pattern of Ig gene expression is mostly biallelic, transcription initiated from nonproductive Ig alleles generates considerable amounts of primary transcripts with out-of-frame V(D)J junctions. How RNA surveillance pathways cooperate to control the noise from nonproductive Ig genes will be discussed in this review, focusing on the benefits of nonsense-mediated mRNA decay (NMD) activation during B-cell development and detrimental effects of nonsense-associated altered splicing (NAS) in terminally differentiated plasma cells.},
pmcid = {PMC6941761}
}
@article{lawrenceDiscoverySaturationAnalysis2014,
title = {Discovery and Saturation Analysis of Cancer Genes across 21 Tumour Types},
author = {Lawrence, Michael S. and Stojanov, Petar and Mermel, Craig H. and Robinson, James T. and Garraway, Levi A. and Golub, Todd R. and Meyerson, Matthew and Gabriel, Stacey B. and Lander, Eric S. and Getz, Gad},
date = {2014-01-23},
journaltitle = {Nature},
shortjournal = {Nature},
volume = {505},
number = {7484},
eprint = {24390350},
eprinttype = {pmid},
pages = {495--501},
issn = {1476-4687},
doi = {10.1038/nature12912},
abstract = {Although a few cancer genes are mutated in a high proportion of tumours of a given type ({$>$}20\%), most are mutated at intermediate frequencies (2-20\%). To explore the feasibility of creating a comprehensive catalogue of cancer genes, we analysed somatic point mutations in exome sequences from 4,742 human cancers and their matched normal-tissue samples across 21 cancer types. We found that large-scale genomic analysis can identify nearly all known cancer genes in these tumour types. Our analysis also identified 33 genes that were not previously known to be significantly mutated in cancer, including genes related to proliferation, apoptosis, genome stability, chromatin regulation, immune evasion, RNA processing and protein homeostasis. Down-sampling analysis indicates that larger sample sizes will reveal many more genes mutated at clinically important frequencies. We estimate that near-saturation may be achieved with 600-5,000 samples per tumour type, depending on background mutation frequency. The results may help to guide the next stage of cancer genomics.},
langid = {english},
pmcid = {PMC4048962},
keywords = {Apoptosis,Case-Control Studies,Cell Proliferation,Chromatin,DNA Mutational Analysis,Exome,Genes Neoplasm,Genome Human,Genomic Instability,Genomics,Humans,Immune Evasion,Mutation Rate,Neoplasms,Point Mutation,RNA Processing Post-Transcriptional,Sample Size}
}
@article{lawrenceMutationalHeterogeneityCancer2013,
title = {Mutational Heterogeneity in Cancer and the Search for New Cancer-Associated Genes},
author = {Lawrence, Michael S. and Stojanov, Petar and Polak, Paz and Kryukov, Gregory V. and Cibulskis, Kristian and Sivachenko, Andrey and Carter, Scott L. and Stewart, Chip and Mermel, Craig H. and Roberts, Steven A. and Kiezun, Adam and Hammerman, Peter S. and McKenna, Aaron and Drier, Yotam and Zou, Lihua and Ramos, Alex H. and Pugh, Trevor J. and Stransky, Nicolas and Helman, Elena and Kim, Jaegil and Sougnez, Carrie and Ambrogio, Lauren and Nickerson, Elizabeth and Shefler, Erica and Cortés, Maria L. and Auclair, Daniel and Saksena, Gordon and Voet, Douglas and Noble, Michael and DiCara, Daniel and Lin, Pei and Lichtenstein, Lee and Heiman, David I. and Fennell, Timothy and Imielinski, Marcin and Hernandez, Bryan and Hodis, Eran and Baca, Sylvan and Dulak, Austin M. and Lohr, Jens and Landau, Dan-Avi and Wu, Catherine J. and Melendez-Zajgla, Jorge and Hidalgo-Miranda, Alfredo and Koren, Amnon and McCarroll, Steven A. and Mora, Jaume and Lee, Ryan S. and Crompton, Brian and Onofrio, Robert and Parkin, Melissa and Winckler, Wendy and Ardlie, Kristin and Gabriel, Stacey B. and Roberts, Charles W. M. and Biegel, Jaclyn A. and Stegmaier, Kimberly and Bass, Adam J. and Garraway, Levi A. and Meyerson, Matthew and Golub, Todd R. and Gordenin, Dmitry A. and Sunyaev, Shamil and Lander, Eric S. and Getz, Gad},
date = {2013-07},
journaltitle = {Nature},
volume = {499},
number = {7457},
pages = {214--218},
issn = {1476-4687},
doi = {10.1038/nature12213},
url = {https://www.nature.com/articles/nature12213},
urldate = {2019-12-21},
abstract = {As the sample size in cancer genome studies increases, the list of genes identified as significantly mutated is likely to include more false positives; here, this problem is identified as stemming largely from mutation heterogeneity, and a new analytical methodology designed to overcome this problem is described.},
langid = {english}
}
@article{leeExpressionInhibitoryFc2015,
title = {Expression of the Inhibitory {{Fc}} Gamma Receptor {{IIB}} ({{FCGR2B}}, {{CD32B}}) on Follicular Lymphoma Cells Lowers the Response Rate to Rituximab Monotherapy ({{SAKK}} 35/98).},
author = {Lee, Chern Siang and Ashton-Key, Margaret and Cogliatti, Sergio and Rondeau, Stephanie and Schmitz, Shu-Fang Hsu and Ghielmini, Michele and Cragg, Mark S and Johnson, Peter},
date = {2015-01},
journaltitle = {Br J Haematol},
volume = {168},
number = {1},
pages = {145--148}
}
@article{leeGainoffunctionMutationsCopy2009,
title = {Gain-of-Function Mutations and Copy Number Increases of {{Notch2}} in Diffuse Large {{B-cell}} Lymphoma.},
author = {Lee, Suk-Young and Kumano, Keiki and Nakazaki, Kumi and Sanada, Masashi and Matsumoto, Akihiko and Yamamoto, Go and Nannya, Yasuhito and Suzuki, Ritsuro and Ota, Satoshi and Ota, Yasunori and Izutsu, Koji and Sakata-Yanagimoto, Mamiko and Hangaishi, Akira and Yagita, Hideo and Fukayama, Masashi and Seto, Masao and Kurokawa, Mineo and Ogawa, Seishi and Chiba, Shigeru},
date = {2009-05},
journaltitle = {Cancer Sci},
volume = {100},
number = {5},
pages = {920--926}
}
@article{lefaveSplicingFactorHnRNPH2011,
title = {Splicing Factor {{hnRNPH}} Drives an Oncogenic Splicing Switch in Gliomas},
author = {LeFave, Clare V and Squatrito, Massimo and Vorlova, Sandra and Rocco, Gina L and Brennan, Cameron W and Holland, Eric C and Pan, Ying-Xian and Cartegni, Luca},
date = {2011-10-05},
journaltitle = {The EMBO Journal},
shortjournal = {The EMBO Journal},
volume = {30},
number = {19},
pages = {4084--4097},
issn = {0261-4189},
doi = {10.1038/emboj.2011.259},
url = {https://www.embopress.org/doi/10.1038/emboj.2011.259},
urldate = {2019-12-21},
abstract = {In tumours, aberrant splicing generates variants that contribute to multiple aspects of tumour establishment, progression and maintenance. We show that in glioblastoma multiforme (GBM) specimens, death-domain adaptor protein Insuloma-Glucagonoma protein 20 (IG20) is consistently aberrantly spliced to generate an antagonist, anti-apoptotic isoform (MAP-kinase activating death domain protein, MADD), which effectively redirects TNF-α/TRAIL-induced death signalling to promote survival and proliferation instead of triggering apoptosis. Splicing factor hnRNPH, which is upregulated in gliomas, controls this splicing event and similarly mediates switching to a ligand-independent, constitutively active Recepteur d?Origine Nantais (RON) tyrosine kinase receptor variant that promotes migration and invasion. The increased cell death and the reduced invasiveness caused by hnRNPH ablation can be rescued by the targeted downregulation of IG20/MADD exon 16- or RON exon 11-containing variants, respectively, using isoform-specific knockdown or splicing redirection approaches. Thus, hnRNPH activity appears to be involved in the pathogenesis and progression of malignant gliomas as the centre of a splicing oncogenic switch, which might reflect reactivation of stem cell patterns and mediates multiple key aspects of aggressive tumour behaviour, including evasion from apoptosis and invasiveness.},
keywords = {antisense,cancer,FSD-NMD,hnRNPH,MADD,RON,splicing}
}
@article{leiCancerMutationD83V2018,
title = {The {{Cancer Mutation D83V Induces}} an α-{{Helix}} to β-{{Strand Conformation Switch}} in {{MEF2B}}},
author = {Lei, Xiao and Kou, Yi and Fu, Yang and Rajashekar, Niroop and Shi, Haoran and Wu, Fang and Xu, Jiang and Luo, Yibing and Chen, Lin},
date = {2018-04-13},
journaltitle = {Journal of Molecular Biology},
shortjournal = {J. Mol. Biol.},
volume = {430},
number = {8},
eprint = {29477338},
eprinttype = {pmid},
pages = {1157--1172},
issn = {1089-8638},
doi = {10.1016/j.jmb.2018.02.012},
abstract = {MEF2B is a major target of somatic mutations in non-Hodgkin lymphoma. Most of these mutations are non-synonymous substitutions of surface residues in the MADS-box/MEF2 domain. Among them, D83V is the most frequent mutation found in tumor cells. The link between this hotspot mutation and cancer is not well understood. Here we show that the D83V mutation induces a dramatic α-helix to β-strand switch in the MEF2 domain. Located in an α-helix region rich in β-branched residues, the D83V mutation not only removes the extensive helix stabilization interactions but also introduces an additional β-branched residue that further shifts the conformation equilibrium from α-helix to β-strand. Cross-database analyses of cancer mutations and chameleon sequences revealed a number of well-known cancer targets harboring β-strand favoring mutations in chameleon α-helices, suggesting a commonality of such conformational switch in certain cancers and a new factor to consider when stratifying the rapidly expanding cancer mutation data.},
langid = {english},
keywords = {Amino Acid Substitution,cancer mutation,Crystallography X-Ray,Humans,lymphoma,Lymphoma Non-Hodgkin,MEF2 Transcription Factors,MEF2B,metamorphic protein structure,Models Molecular,Protein Conformation alpha-Helical,Protein Conformation beta-Strand,protein conformation change,Protein Domains}
}
@article{lenzMolecularSubtypesDiffuse2008,
title = {Molecular Subtypes of Diffuse Large {{B-cell}} Lymphoma Arise by Distinct Genetic Pathways},
author = {Lenz, Georg and Wright, George W. and Emre, N. C. Tolga and Kohlhammer, Holger and Dave, Sandeep S. and Davis, R. Eric and Carty, Shannon and Lam, Lloyd T. and Shaffer, A. L. and Xiao, Wenming and Powell, John and Rosenwald, Andreas and Ott, German and Muller-Hermelink, Hans Konrad and Gascoyne, Randy D. and Connors, Joseph M. and Campo, Elias and Jaffe, Elaine S. and Delabie, Jan and Smeland, Erlend B. and Rimsza, Lisa M. and Fisher, Richard I. and Weisenburger, Dennis D. and Chan, Wing C. and Staudt, Louis M.},
date = {2008-09-09},
journaltitle = {Proceedings of the National Academy of Sciences},
shortjournal = {Proc Natl Acad Sci},
volume = {105},
number = {36},
eprint = {18765795},
eprinttype = {pmid},
pages = {13520--13525},
issn = {1091-6490},
doi = {10.1073/pnas.0804295105},
abstract = {Gene-expression profiling has been used to define 3 molecular subtypes of diffuse large B-cell lymphoma (DLBCL), termed germinal center B-cell-like (GCB) DLBCL, activated B-cell-like (ABC) DLBCL, and primary mediastinal B-cell lymphoma (PMBL). To investigate whether these DLBCL subtypes arise by distinct pathogenetic mechanisms, we analyzed 203 DLBCL biopsy samples by high-resolution, genome-wide copy number analysis coupled with gene-expression profiling. Of 272 recurrent chromosomal aberrations that were associated with gene-expression alterations, 30 were used differentially by the DLBCL subtypes (P {$<$} 0.006). An amplicon on chromosome 19 was detected in 26\% of ABC DLBCLs but in only 3\% of GCB DLBCLs and PMBLs. A highly up-regulated gene in this amplicon was SPIB, which encodes an ETS family transcription factor. Knockdown of SPIB by RNA interference was toxic to ABC DLBCL cell lines but not to GCB DLBCL, PMBL, or myeloma cell lines, strongly implicating SPIB as an oncogene involved in the pathogenesis of ABC DLBCL. Deletion of the INK4a/ARF tumor suppressor locus and trisomy 3 also occurred almost exclusively in ABC DLBCLs and was associated with inferior outcome within this subtype. FOXP1 emerged as a potential oncogene in ABC DLBCL that was up-regulated by trisomy 3 and by more focal high-level amplifications. In GCB DLBCL, amplification of the oncogenic mir-17-92 microRNA cluster and deletion of the tumor suppressor PTEN were recurrent, but these events did not occur in ABC DLBCL. Together, these data provide genetic evidence that the DLBCL subtypes are distinct diseases that use different oncogenic pathways.},
langid = {english},
pmcid = {PMC2533222},
keywords = {Biopsy,Cell Survival,Chromosome Aberrations,Gene Expression Profiling,Gene Expression Regulation Neoplastic,Genome Human,Humans,Lymphoma Large B-Cell Diffuse,Oncogene Proteins,Prognosis,Tumor Suppressor Proteins}
}
@article{lenzOncogenicCARD11Mutations2008,
title = {Oncogenic {{CARD11}} Mutations in Human Diffuse Large {{B}} Cell Lymphoma.},
author = {Lenz, Georg and Davis, R Eric and Ngo, Vu N and Lam, Lloyd and George, Thaddeus C and Wright, George W and Dave, Sandeep S and Zhao, Hong and Xu, Weihong and Rosenwald, Andreas and Ott, German and Müller-Hermelink, Hans-Konrad and Gascoyne, Randy D and Connors, Joseph M and Rimsza, Lisa M and Campo, Elias and Jaffe, Elaine S and Delabie, Jan and Smeland, Erlend B and Fisher, Richard I and Chan, Wing C and Staudt, Louis M},
date = {2008-03},
journaltitle = {Science},
volume = {319},
number = {5870},
pages = {1676--1679},
doi = {10.1126/science.1153629}
}
@article{lenzStromalGeneSignatures2008,
title = {Stromal Gene Signatures in Large-{{B-cell}} Lymphomas},
author = {Lenz, G. and Wright, G. and Dave, S. S. and Xiao, W. and Powell, J. and Zhao, H. and Xu, W. and Tan, B. and Goldschmidt, N. and Iqbal, J. and Vose, J. and Bast, M. and Fu, K. and Weisenburger, D. D. and Greiner, T. C. and Armitage, J. O. and Kyle, A. and May, L. and Gascoyne, R. D. and Connors, J. M. and Troen, G. and Holte, H. and Kvaloy, S. and Dierickx, D. and Verhoef, G. and Delabie, J. and Smeland, E. B. and Jares, P. and Martinez, A. and Lopez-Guillermo, A. and Montserrat, E. and Campo, E. and Braziel, R. M. and Miller, T. P. and Rimsza, L. M. and Cook, J. R. and Pohlman, B. and Sweetenham, J. and Tubbs, R. R. and Fisher, R. I. and Hartmann, E. and Rosenwald, A. and Ott, G. and Muller-Hermelink, H.-K. and Wrench, D. and Lister, T. A. and Jaffe, E. S. and Wilson, W. H. and Chan, W. C. and Staudt, L. M. and {Lymphoma/Leukemia Molecular Profiling Project}},
date = {2008-11-27},
journaltitle = {The New England Journal of Medicine},
shortjournal = {N. Engl. J. Med.},
volume = {359},
number = {22},
eprint = {19038878},
eprinttype = {pmid},
pages = {2313--2323},
issn = {1533-4406},
doi = {10.1056/NEJMoa0802885},
abstract = {BACKGROUND: The addition of rituximab to combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), or R-CHOP, has significantly improved the survival of patients with diffuse large-B-cell lymphoma. Whether gene-expression signatures correlate with survival after treatment of diffuse large-B-cell lymphoma is unclear. METHODS: We profiled gene expression in pretreatment biopsy specimens from 181 patients with diffuse large-B-cell lymphoma who received CHOP and 233 patients with this disease who received R-CHOP. A multivariate gene-expression-based survival-predictor model derived from a training group was tested in a validation group. RESULTS: A multivariate model created from three gene-expression signatures--termed "germinal-center B-cell," "stromal-1," and "stromal-2"--predicted survival both in patients who received CHOP and patients who received R-CHOP. The prognostically favorable stromal-1 signature reflected extracellular-matrix deposition and histiocytic infiltration. By contrast, the prognostically unfavorable stromal-2 signature reflected tumor blood-vessel density. CONCLUSIONS: Survival after treatment of diffuse large-B-cell lymphoma is influenced by differences in immune cells, fibrosis, and angiogenesis in the tumor microenvironment.},
langid = {english},
keywords = {Antibodies Monoclonal,Antibodies Monoclonal Murine-Derived,Antineoplastic Combined Chemotherapy Protocols,Cyclophosphamide,Disease Progression,Doxorubicin,Extracellular Matrix,Gene Expression,Gene Expression Profiling,Gene Expression Regulation Neoplastic,Genes MHC Class II,Germinal Center,Humans,Immunologic Factors,Kaplan-Meier Estimate,Lymphoma Large B-Cell Diffuse,Middle Aged,Multivariate Analysis,Neovascularization Pathologic,Prednisone,Prognosis,Rituximab,Stromal Cells,Vincristine}
}
@article{liAptamerBC15Heterogeneous2012,
title = {Aptamer {{BC15}} against Heterogeneous Nuclear Ribonucleoprotein {{A1}} Has Potential Value in Diagnosis and Therapy of Hepatocarcinoma},
author = {Li, Shaohua and Wang, Wei and Ding, Hongmei and Xu, Hua and Zhao, Qiang and Li, Jie and Li, Hui and Xia, Wei and Su, Xueting and Chen, Ying and Fang, Tao and Shao, Ningsheng and Zhang, Hongwen},
date = {2012-12},
journaltitle = {Nucleic Acid Therapeutics},
shortjournal = {Nucleic Acid Ther},
volume = {22},
number = {6},
eprint = {23062008},
eprinttype = {pmid},
pages = {391--398},
issn = {2159-3345},
doi = {10.1089/nat.2012.0363},
abstract = {The heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) was reported to be participated in tumor development. The association between hnRNP A1 and liver cancer and the functional role of hnRNP A1 in liver cancer have never been reported. Herein, hnRNP A1-specific single-stranded DNA aptamer, BC15, was used to (a) evaluate hnRNP A1 expression in liver cancer, and (b) treat hepatocarcinoma by acting as an inhibitor of hnRNP A1. Results showed that there is high hnRNP A1 expression in liver cancer including serum α-fetoprotein-negative liver cancer tissues compared with either para-cancer or benign controls. Down regulation of hnRNP A1 expression by RNA interference inhibits the proliferation and migration of cancerous HepG2 cells, while overexpression of hnRNP A1 in normal HL-7702 cells increased the proliferation and migration of the cells. Importantly, BC15 showed a stronger inhibiting effect on the proliferation of cultured hepatoma cells than hnRNP A1 small interfering RNA, strongly suggesting that BC15 could also be a potential drug candidate for an hnRNP A1 inhibitor besides its prospect utility in in situ histological examination.},
langid = {english},
keywords = {Animals,Antineoplastic Agents,Aptamers Nucleotide,Carcinoma Hepatocellular,Cell Line Tumor,Cell Movement,Cell Proliferation,Gene Knockdown Techniques,Hep G2 Cells,Heterogeneous Nuclear Ribonucleoprotein A1,Heterogeneous-Nuclear Ribonucleoprotein Group A-B,Humans,Liver Neoplasms,Mice,Mice Nude,Neoplasm Invasiveness,RNA Small Interfering,Xenograft Model Antitumor Assays}
}
@article{liEffectsLongNoncoding2017,
title = {The Effects of the Long Non-Coding {{RNA MALAT-1}} Regulated Autophagy-Related Signaling Pathway on Chemotherapy Resistance in Diffuse Large {{B-cell}} Lymphoma},
author = {Li, Li-Juan and Chai, Ye and Guo, Xiao-Jia and Chu, Song-Lin and Zhang, Lian-Sheng},
date = {2017-05},
journaltitle = {Biomedicine \& Pharmacotherapy},
volume = {89},
pages = {939--948}
}
@article{lienAtlanticSalmonGenome2016,
title = {The {{Atlantic}} Salmon Genome Provides Insights into Rediploidization},
author = {Lien, Sigbjørn and Koop, Ben F. and Sandve, Simen R. and Miller, Jason R. and Kent, Matthew P. and Nome, Torfinn and Hvidsten, Torgeir R. and Leong, Jong S. and Minkley, David R. and Zimin, Aleksey and Grammes, Fabian and Grove, Harald and Gjuvsland, Arne and Walenz, Brian and Hermansen, Russell A. and family=Schalburg, given=Kris, prefix=von, useprefix=true and Rondeau, Eric B. and Di Genova, Alex and Samy, Jeevan K. A. and Olav Vik, Jon and Vigeland, Magnus D. and Caler, Lis and Grimholt, Unni and Jentoft, Sissel and Våge, Dag Inge and family=Jong, given=Pieter, prefix=de, useprefix=true and Moen, Thomas and Baranski, Matthew and Palti, Yniv and Smith, Douglas R. and Yorke, James A. and Nederbragt, Alexander J. and Tooming-Klunderud, Ave and Jakobsen, Kjetill S. and Jiang, Xuanting and Fan, Dingding and Hu, Yan and Liberles, David A. and Vidal, Rodrigo and Iturra, Patricia and Jones, Steven J. M. and Jonassen, Inge and Maass, Alejandro and Omholt, Stig W. and Davidson, William S.},
date = {2016-12-05},
journaltitle = {Nature},
shortjournal = {Nature},
volume = {533},
number = {7602},
eprint = {27088604},
eprinttype = {pmid},
pages = {200--205},
issn = {1476-4687},
doi = {10.1038/nature17164},
abstract = {The whole-genome duplication 80 million years ago of the common ancestor of salmonids (salmonid-specific fourth vertebrate whole-genome duplication, Ss4R) provides unique opportunities to learn about the evolutionary fate of a duplicated vertebrate genome in 70 extant lineages. Here we present a high-quality genome assembly for Atlantic salmon (Salmo salar), and show that large genomic reorganizations, coinciding with bursts of transposon-mediated repeat expansions, were crucial for the post-Ss4R rediploidization process. Comparisons of duplicate gene expression patterns across a wide range of tissues with orthologous genes from a pre-Ss4R outgroup unexpectedly demonstrate far more instances of neofunctionalization than subfunctionalization. Surprisingly, we find that genes that were retained as duplicates after the teleost-specific whole-genome duplication 320 million years ago were not more likely to be retained after the Ss4R, and that the duplicate retention was not influenced to a great extent by the nature of the predicted protein interactions of the gene products. Finally, we demonstrate that the Atlantic salmon assembly can serve as a reference sequence for the study of other salmonids for a range of purposes.},
langid = {english},
keywords = {Animals,Diploidy,DNA Transposable Elements,Evolution Molecular,Female,Gene Duplication,Genes Duplicate,Genome,Genomics,Male,Models Genetic,Mutagenesis,Phylogeny,Reference Standards,Salmo salar,Sequence Homology}
}
@article{lindenblattIkBzExpressionRegulated2014,
title = {{{IκBζ}} Expression Is Regulated by {{miR-124a}}},
author = {Lindenblatt, Charlotte and Schulze-Osthoff, Klaus and Totzke, Gudrun},
date = {2014-10},
journaltitle = {Cell Cycle (Georgetown, Tex.)},
volume = {8},
number = {13},
pages = {2019--2023}
}
@article{linNovelNucleocytoplasmicShuttling2006,
title = {A Novel Nucleocytoplasmic Shuttling Sequence of {{DAZAP1}}, a Testis-Abundant {{RNA-binding}} Protein},
author = {Lin, Yi-Tzu and Yen, Pauline H.},
date = {2006-08},
journaltitle = {RNA (New York, N.Y.)},
shortjournal = {RNA},
volume = {12},
number = {8},
eprint = {16772659},
eprinttype = {pmid},
pages = {1486--1493},
issn = {1355-8382},
doi = {10.1261/rna.42206},
abstract = {Deleted in Azoospermia Associated Protein 1 (DAZAP1) is a ubiquitous RNA-binding protein highly expressed in the human and the mouse testes. It shows a dynamic subcellular localization during spermatogenesis, present predominantly in the nuclei of late-stage spermatocytes and round spermatids and translocated to the cytoplasm during spermatid elongation. To test the hypothesis that DAZAP1 shuttles between the nucleus and the cytoplasm, we studied the nuclear transport of DAZAP1 in somatic cells using immunostaining, heterokaryon formation, and mutagenesis. DAZAP1 is detected exclusively in the nucleus and has the ability to shuttle between the nucleus and the cytoplasm using a highly conserved 25 amino acid segment, designated ZNS, at its C terminus. ZNS shares no sequence homology with other known nuclear localization or export signals. Attachment of ZNS to a red fluorescent protein DsRed2 confers the nucleocytoplasmic shuttling ability to that protein. The nuclear localization of DAZAP1 depends on active transcription. In the presence of an RNA polymerase II inhibitor, DAZAP1 is retained in the cytoplasm. DAZAP1 colocalizes with hnRNP A1 and hnRNP C1 in the nucleus and is a component of the heterogeneous nuclear ribonucleoprotein particles. Our results suggest that DAZAP1 plays a key role in mRNA transport during spermatogenesis.},
langid = {english},
pmcid = {PMC1524892},
keywords = {3T3 Cells,Active Transport Cell Nucleus,Amino Acid Sequence,Animals,Cell Line,Cell Nucleus,Cercopithecus aethiops,Conserved Sequence,COS Cells,Cytoplasm,Dactinomycin,HeLa Cells,Heterogeneous Nuclear Ribonucleoprotein A1,Heterogeneous-Nuclear Ribonucleoprotein Group A-B,Heterogeneous-Nuclear Ribonucleoprotein Group C,Humans,Male,Mice,Molecular Sequence Data,Mutagenesis Site-Directed,Mutation,Nuclear Localization Signals,Recombinant Fusion Proteins,RNA-Binding Proteins,Testis,Transcription Genetic}
}
@article{liPolyRCBinding,
title = {Poly({{rC}}) {{Binding Protein}} 1 {{Represses}} the {{Translation}} of {{STAT3}} through 5' {{UTR}}},
author = {Li, Ziwei and Wang, Xiaole and Jia, Rong},
journaltitle = {Current Gene Therapy},
volume = {22},
number = {5},
pages = {397--405},
url = {https://benthamscience.com/article/123400},
urldate = {2022-09-28},
abstract = {Background: Signal transducer and activator of transcription 3 (STAT3) is an oncogene and frequently overexpressed in cancers. However, the regulatory mechanisms of STAT3 expression are not fully understood. Poly(rC)-binding protein1 (PCBP1) is an RNA-binding protein that regulates mRNA stability, splicing, and translation. PCBP1 is a tumor suppressor and can inhibit the translation of several oncogenic genes. Objective: We aimed to understand the regulatory mechanisms of STAT3 expression. Methods: The 5' UTR or 3’ UTR regions of the human STAT3 gene were inserted upstream or downstream of the green fluorescent gene (GFP), respectively, which were used as reporter systems to analyze the inhibitory effects of PCBP1 on the STAT3 gene expression. The deletion and point mutation in 5' UTR were used to search the essential regulatory sequences of the translation inhibition. The mutations of PCBP1 protein were analyzed in the cBioPortal online service. The effects of mutated PCBP1 proteins on STAT3 expression, cancer cell proliferation, and colony formation were analyzed in oral squamous cell carcinoma (OSCC) cell lines. Results: PCBP1 inhibits mRNA translation through a motif in the 5' UTR of STAT3. Moreover, we found two leucine residues (Leu100 and Leu102) of PCBP1 protein frequently mutated in cancers. These mutations abolished the inhibition function of PCBP1 on STAT3 translation. Surprisingly, in contrast to wild-type PCBP1 protein, these mutations can promote the growth and colony formation of cancer cells. Conclusion: Overall, we demonstrate that PCBP1 can inhibit the expression of STAT3 through its 5' UTR, and two leucine residues of PCBP1 protein are essential for its functions.},
langid = {english}
}
@article{liuGerminalCenterCells1991,
title = {Germinal Center Cells Express Bcl-2 Protein after Activation by Signals Which Prevent Their Entry into Apoptosis},
author = {Liu, Y. J. and Mason, D. Y. and Johnson, G. D. and Abbot, S. and Gregory, C. D. and Hardie, D. L. and Gordon, J. and MacLennan, I. C.},
date = {1991-08},
journaltitle = {European Journal of Immunology},
shortjournal = {Eur J Immunol},
volume = {21},
number = {8},
eprint = {1868875},
eprinttype = {pmid},
pages = {1905--1910},
issn = {0014-2980},
doi = {10.1002/eji.1830210819},
abstract = {B cells undergo selection within germinal centers on the basis of their capacity to be activated by antigen held on follicular dendritic cells. Isolated germinal center B cells in culture kill themselves by apoptosis but this is prevented if their receptors for antigen are cross-linked. In this study it is confirmed that almost all germinal center B cells, unlike other B cells, do not express the 25-kDa protein encoded by the bcl-2 oncogene. Cross-linking the surface Ig of isolated germinal center cells causes them to express bcl-2 protein. Two other stimuli which inhibit the entry of germinal center cells to apoptosis result in the expression of bcl-2 protein. These stimuli are: (a) CD40 antibody and (b) recombinant 25-kDa fragment of the CD23 protein plus recombinant interleukin 1 alpha. Respectively, these induce germinal center cells to differentiate to resting B cells or plasmablasts. Dual-fluorescence studies on small lymphocytes confirm the presence of bcl-2 protein in mitochondria but show that this is also present in other extra-nuclear areas. Burkitt lymphoma cells have a phenotype which indicates that they are neoplastic cells of germinal center origin. The expression of bcl-2 protein by Burkitt lymphoma lines was also studied. Burkitt lines which retain the phenotype of fresh Burkitt lymphoma cells can be induced to enter apoptosis on culture with the Ca2+ ionophore ionomycin. These cells were found not to express bcl-2 protein. By contrast, Burkitt lines which have drifted towards a lymphoblastoid cell line phenotype and are resistant to the induction of apoptosis express high levels of the bcl-2 protein. The findings support the concept that the susceptibility of germinal center cells to entering apoptosis is associated with their lack of expression of bcl-2 protein. Aberrant expression of bcl-2 protein by some neoplastic germinal center cells may allow survival in situations where their normal counterparts die.},
langid = {english},
keywords = {Antibodies Monoclonal,B-Lymphocytes,Burkitt Lymphoma,Cell Survival,Cells Cultured,Humans,Mitochondria,Proto-Oncogene Proteins,Proto-Oncogene Proteins c-bcl-2}
}
@article{lohrDiscoveryPrioritizationSomatic2012,
title = {Discovery and Prioritization of Somatic Mutations in Diffuse Large {{B-cell}} Lymphoma ({{DLBCL}}) by Whole-Exome Sequencing},
author = {Lohr, Jens G. and Stojanov, Petar and Lawrence, Michael S. and Auclair, Daniel and Chapuy, Bjoern and Sougnez, Carrie and Cruz-Gordillo, Peter and Knoechel, Birgit and Asmann, Yan W. and Slager, Susan L. and Novak, Anne J. and Dogan, Ahmet and Ansell, Stephen M. and Link, Brian K. and Zou, Lihua and Gould, Joshua and Saksena, Gordon and Stransky, Nicolas and Rangel-Escareño, Claudia and Fernandez-Lopez, Juan Carlos and Hidalgo-Miranda, Alfredo and Melendez-Zajgla, Jorge and Hernández-Lemus, Enrique and Schwarz-Cruz y Celis, Angela and Imaz-Rosshandler, Ivan and Ojesina, Akinyemi I. and Jung, Joonil and Pedamallu, Chandra S. and Lander, Eric S. and Habermann, Thomas M. and Cerhan, James R. and Shipp, Margaret A. and Getz, Gad and Golub, Todd R.},
date = {2012-03-06},
journaltitle = {Proceedings of the National Academy of Sciences of the United States of America},
shortjournal = {Proc Natl Acad Sci U S A},
volume = {109},
number = {10},
eprint = {22343534},
eprinttype = {pmid},
pages = {3879--3884},
issn = {1091-6490},
doi = {10.1073/pnas.1121343109},
abstract = {To gain insight into the genomic basis of diffuse large B-cell lymphoma (DLBCL), we performed massively parallel whole-exome sequencing of 55 primary tumor samples from patients with DLBCL and matched normal tissue. We identified recurrent mutations in genes that are well known to be functionally relevant in DLBCL, including MYD88, CARD11, EZH2, and CREBBP. We also identified somatic mutations in genes for which a functional role in DLBCL has not been previously suspected. These genes include MEF2B, MLL2, BTG1, GNA13, ACTB, P2RY8, PCLO, and TNFRSF14. Further, we show that BCL2 mutations commonly occur in patients with BCL2/IgH rearrangements as a result of somatic hypermutation normally occurring at the IgH locus. The BCL2 point mutations are primarily synonymous, and likely caused by activation-induced cytidine deaminase-mediated somatic hypermutation, as shown by comprehensive analysis of enrichment of mutations in WRCY target motifs. Those nonsynonymous mutations that are observed tend to be found outside of the functionally important BH domains of the protein, suggesting that strong negative selection against BCL2 loss-of-function mutations is at play. Last, by using an algorithm designed to identify likely functionally relevant but infrequent mutations, we identify KRAS, BRAF, and NOTCH1 as likely drivers of DLBCL pathogenesis in some patients. Our data provide an unbiased view of the landscape of mutations in DLBCL, and this in turn may point toward new therapeutic strategies for the disease.},
langid = {english},
pmcid = {PMC3309757},
keywords = {Amino Acid Motifs,Cluster Analysis,DNA Mutational Analysis,Exome,Exons,Gene Expression Regulation Neoplastic,Humans,Lymphoma Large B-Cell Diffuse,Models Genetic,Mutation,Polymerase Chain Reaction,Sequence Analysis DNA,Translocation Genetic}
}
@article{lopezGenomicTranscriptomicChanges2019,
title = {Genomic and Transcriptomic Changes Complement Each Other in the Pathogenesis of Sporadic {{Burkitt}} Lymphoma},
author = {López, Cristina and Kleinheinz, Kortine and Aukema, Sietse M. and Rohde, Marius and Bernhart, Stephan H. and Hübschmann, Daniel and Wagener, Rabea and Toprak, Umut H. and Raimondi, Francesco and Kreuz, Markus and Waszak, Sebastian M. and Huang, Zhiqin and Sieverling, Lina and Paramasivam, Nagarajan and Seufert, Julian and Sungalee, Stephanie and Russell, Robert B. and Bausinger, Julia and Kretzmer, Helene and Ammerpohl, Ole and Bergmann, Anke K. and Binder, Hans and Borkhardt, Arndt and Brors, Benedikt and Claviez, Alexander and Doose, Gero and Feuerbach, Lars and Haake, Andrea and Hansmann, Martin-Leo and Hoell, Jessica and Hummel, Michael and Korbel, Jan O. and Lawerenz, Chris and Lenze, Dido and Radlwimmer, Bernhard and Richter, Julia and Rosenstiel, Philip and Rosenwald, Andreas and Schilhabel, Markus B. and Stein, Harald and Stilgenbauer, Stephan and Stadler, Peter F. and Szczepanowski, Monika and Weniger, Marc A. and Zapatka, Marc and Eils, Roland and Lichter, Peter and Loeffler, Markus and Möller, Peter and Trümper, Lorenz and Klapper, Wolfram and Hoffmann, Steve and Küppers, Ralf and Burkhardt, Birgit and Schlesner, Matthias and Siebert, Reiner},
date = {2019-03-29},
journaltitle = {Nature Communications},
shortjournal = {Nat Commun},
volume = {10},
number = {1},
pages = {1459},
publisher = {Nature Publishing Group},
issn = {2041-1723},
doi = {10.1038/s41467-019-08578-3},
url = {https://www.nature.com/articles/s41467-019-08578-3},
urldate = {2021-11-30},
abstract = {Burkitt lymphoma (BL) is the most common B-cell lymphoma in children. Within the International Cancer Genome Consortium (ICGC), we performed whole genome and transcriptome sequencing of 39 sporadic BL. Here, we unravel~interaction of structural, mutational, and transcriptional changes, which contribute to MYC oncogene dysregulation together with the pathognomonic IG-MYC translocation. Moreover, by mapping IGH translocation breakpoints, we provide evidence that the precursor of at least a subset of BL is a B-cell poised to express IGHA. We describe the landscape of mutations, structural variants, and mutational processes, and identified a series of driver genes in the pathogenesis of BL, which can be targeted by various mechanisms, including IG-non MYC translocations, germline and somatic mutations, fusion transcripts, and alternative splicing.},
issue = {1},
langid = {english},
keywords = {Cancer genomics,Lymphocytes,Lymphoid tissues,Oncology}
}
@article{lossosAIDExpressedGerminal2004,
title = {{{AID}} Is Expressed in Germinal Center {{B-cell-like}} and Activated {{B-cell-like}} Diffuse Large-Cell Lymphomas and Is Not Correlated with Intraclonal Heterogeneity},
author = {Lossos, I S and Levy, R and Alizadeh, A A},
date = {2004-09},
journaltitle = {Leukemia},
volume = {18},
number = {11},
pages = {1775--1779}
}
@article{lossosHGALNovelInterleukin4inducible2003,
title = {{{HGAL}} Is a Novel Interleukin-4-Inducible Gene That Strongly Predicts Survival in Diffuse Large {{B-cell}} Lymphoma},
author = {Lossos, I S},
date = {2003-01},
journaltitle = {Blood},
volume = {101},
number = {2},
pages = {433--440}
}
@article{lossosMolecularPathogenesisDiffuse2005,
title = {Molecular {{Pathogenesis}} of {{Diffuse Large B-Cell Lymphoma}}},
author = {Lossos, I S},
date = {2005-09},
journaltitle = {J Clin Oncol},
volume = {23},
number = {26},
pages = {6351--6357}
}
@article{lossosOngoingImmunoglobulinSomatic2000,
title = {Ongoing Immunoglobulin Somatic Mutation in Germinal Center {{B}} Cell-like but Not in Activated {{B}} Cell-like Diffuse Large Cell Lymphomas},
author = {Lossos, I S and Alizadeh, A A and Eisen, M B and Chan, W C and Brown, P O and Botstein, D and Staudt, L M and Levy, R},
date = {2000-08},
volume = {97},
number = {18},
pages = {10209--10213}
}
@article{lossosPredictionSurvivalDiffuse2004,
title = {Prediction of {{Survival}} in {{Diffuse Large-B-Cell Lymphoma Based}} on the {{Expression}} of {{Six Genes}}},
author = {Lossos, Izidore S and Czerwinski, Debra K and Alizadeh, Ash A and Wechser, Mark A and Tibshirani, Rob and Botstein, David and Levy, Ronald},
date = {2004-04},
journaltitle = {N Engl J Med},
volume = {350},
number = {18},
pages = {1828--1837}
}
@article{louissaintPediatrictypeNodalFollicular2016,
title = {Pediatric-Type Nodal Follicular Lymphoma: A Biologically Distinct Lymphoma with Frequent {{MAPK}} Pathway Mutations},
shorttitle = {Pediatric-Type Nodal Follicular Lymphoma},
author = {Louissaint, Abner and Schafernak, Kristian T. and Geyer, Julia T. and Kovach, Alexandra E. and Ghandi, Mahmoud and Gratzinger, Dita and Roth, Christine G. and Paxton, Christian N. and Kim, Sunhee and Namgyal, Chungdak and Morin, Ryan and Morgan, Elizabeth A. and Neuberg, Donna S. and South, Sarah T. and Harris, Marian H. and Hasserjian, Robert P. and Hochberg, Ephraim P. and Garraway, Levi A. and Harris, Nancy Lee and Weinstock, David M.},
date = {2016-08-25},
journaltitle = {Blood},
shortjournal = {Blood},
volume = {128},
number = {8},
eprint = {27325104},
eprinttype = {pmid},
pages = {1093--1100},
issn = {1528-0020},
doi = {10.1182/blood-2015-12-682591},
abstract = {Pediatric-type nodal follicular lymphoma (PTNFL) is a variant of follicular lymphoma (FL) characterized by limited-stage presentation and invariably benign behavior despite often high-grade histological appearance. It is important to distinguish PTNFL from typical FL in order to avoid unnecessary treatment; however, this distinction relies solely on clinical and pathological criteria, which may be variably applied. To define the genetic landscape of PTNFL, we performed copy number analysis and exome and/or targeted sequencing of 26 PTNFLs (16 pediatric and 10 adult). The most commonly mutated gene in PTNFL was MAP2K1, encoding MEK1, with a mutation frequency of 43\%. All MAP2K1 mutations were activating missense mutations localized to exons 2 and 3, which encode negative regulatory and catalytic domains, respectively. Missense mutations in MAPK1 (2/22) and RRAS (1/22) were identified in cases that lacked MAP2K1 mutations. The second most commonly mutated gene in PTNFL was TNFRSF14, with a mutation frequency of 29\%, similar to that seen in limited-stage typical FL (P = .35). PTNFL was otherwise genomically bland and specifically lacked recurrent mutations in epigenetic modifiers (eg, CREBBP, KMT2D). Copy number aberrations affected a mean of only 0.5\% of PTNFL genomes, compared with 10\% of limited-stage typical FL genomes (P {$<$} .02). Importantly, the mutational profiles of PTNFLs in children and adults were highly similar. Together, these findings define PTNFL as a biologically and clinically distinct indolent lymphoma of children and adults characterized by a high prevalence of MAPK pathway mutations and a near absence of mutations in epigenetic modifiers.},
langid = {english},
pmcid = {PMC5000844},
keywords = {Adolescent,Age Factors,Cell Shape,Child,Child Preschool,DNA Copy Number Variations,Epigenesis Genetic,Female,Humans,Immunophenotyping,Infant,Lymphoma Follicular,Male,MAP Kinase Signaling System,Mutation}
}
@article{loveGeneticLandscapeMutations2012,
title = {The Genetic Landscape of Mutations in {{Burkitt}} Lymphoma},
author = {Love, Cassandra and Sun, Zhen and Jima, Dereje and Li, Guojie and Zhang, Jenny and Miles, Rodney and Richards, Kristy L. and Dunphy, Cherie H. and Choi, William W. L. and Srivastava, Gopesh and Lugar, Patricia L. and Rizzieri, David A. and Lagoo, Anand S. and Bernal-Mizrachi, Leon and Mann, Karen P. and Flowers, Christopher R. and Naresh, Kikkeri N. and Evens, Andrew M. and Chadburn, Amy and Gordon, Leo I. and Czader, Magdalena B. and Gill, Javed I. and Hsi, Eric D. and Greenough, Adrienne and Moffitt, Andrea B. and McKinney, Matthew and Banerjee, Anjishnu and Grubor, Vladimir and Levy, Shawn and Dunson, David B. and Dave, Sandeep S.},
date = {2012-12},
journaltitle = {Nature Genetics},
shortjournal = {Nat Genet},
volume = {44},
number = {12},
eprint = {23143597},
eprinttype = {pmid},
pages = {1321--1325},
issn = {1546-1718},
doi = {10.1038/ng.2468},
abstract = {Burkitt lymphoma is characterized by deregulation of MYC, but the contribution of other genetic mutations to the disease is largely unknown. Here, we describe the first completely sequenced genome from a Burkitt lymphoma tumor and germline DNA from the same affected individual. We further sequenced the exomes of 59 Burkitt lymphoma tumors and compared them to sequenced exomes from 94 diffuse large B-cell lymphoma (DLBCL) tumors. We identified 70 genes that were recurrently mutated in Burkitt lymphomas, including ID3, GNA13, RET, PIK3R1 and the SWI/SNF genes ARID1A and SMARCA4. Our data implicate a number of genes in cancer for the first time, including CCT6B, SALL3, FTCD and PC. ID3 mutations occurred in 34\% of Burkitt lymphomas and not in DLBCLs. We show experimentally that ID3 mutations promote cell cycle progression and proliferation. Our work thus elucidates commonly occurring gene-coding mutations in Burkitt lymphoma and implicates ID3 as a new tumor suppressor gene.},
langid = {english},
pmcid = {PMC3674561},
keywords = {Ammonia-Lyases,Base Sequence,Burkitt Lymphoma,Cell Line Tumor,Chaperonin Containing TCP-1,DNA Helicases,DNA-Binding Proteins,Genes myc,Genome Human,Glutamate Formimidoyltransferase,GTP-Binding Protein alpha Subunits G12-G13,Homeodomain Proteins,Humans,Inhibitor of Differentiation Proteins,Intracellular Signaling Peptides and Proteins,Lymphoma Large B-Cell Diffuse,Membrane Proteins,Molecular Sequence Data,Multifunctional Enzymes,Mutation,Neoplasm Proteins,Nuclear Proteins,Proto-Oncogene Proteins c-ret,Sequence Analysis DNA,Transcription Factors,Translocation Genetic}
}
@article{loveModeratedEstimationFold2014,
title = {Moderated Estimation of Fold Change and Dispersion for {{RNA-seq}} Data with {{DESeq2}}},
author = {Love, Michael I. and Huber, Wolfgang and Anders, Simon},
date = {2014},
journaltitle = {Genome Biology},
shortjournal = {Genome Biol.},
volume = {15},
number = {12},
eprint = {25516281},
eprinttype = {pmid},
pages = {550},
issn = {1474-760X},
doi = {10.1186/s13059-014-0550-8},
abstract = {In comparative high-throughput sequencing assays, a fundamental task is the analysis of count data, such as read counts per gene in RNA-seq, for evidence of systematic changes across experimental conditions. Small replicate numbers, discreteness, large dynamic range and the presence of outliers require a suitable statistical approach. We present DESeq2, a method for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates. This enables a more quantitative analysis focused on the strength rather than the mere presence of differential expression. The DESeq2 package is available at http://www.bioconductor.org/packages/release/bioc/html/DESeq2.html webcite.},
langid = {english},
pmcid = {PMC4302049},
keywords = {Algorithms,Computational Biology,High-Throughput Nucleotide Sequencing,Models Genetic,RNA,Sequence Analysis RNA,Software}
}
@article{luMCPIP1SelectivelyDestabilizes2016,
title = {{{MCPIP1 Selectively Destabilizes Transcripts Associated}} with an {{Antiapoptotic Gene Expression Program}} in {{Breast Cancer Cells That Can Elicit Complete Tumor Regression}}},
author = {Lu, W and Ning, H and Gu, L and Peng, H and Wang, Q and Hou, R and Fu, M and Hoft, D F and Liu, J},
date = {2016-03},
journaltitle = {Cancer Res},
volume = {76},
number = {6},
pages = {1429--1440}
}
@article{luoMultitaskConvolutionalDeep2019,
title = {A Multi-Task Convolutional Deep Neural Network for Variant Calling in Single Molecule Sequencing},
author = {Luo, Ruibang and Sedlazeck, Fritz J. and Lam, Tak-Wah and Schatz, Michael C.},
date = {2019-03-01},
journaltitle = {Nature Communications},
shortjournal = {Nat Commun},
volume = {10},
number = {1},
eprint = {30824707},
eprinttype = {pmid},
pages = {998},
issn = {2041-1723},
doi = {10.1038/s41467-019-09025-z},
abstract = {The accurate identification of DNA sequence variants is an important, but challenging task in genomics. It is particularly difficult for single molecule sequencing, which has a per-nucleotide error rate of \textasciitilde 5-15\%. Meeting this demand, we developed Clairvoyante, a multi-task five-layer convolutional neural network model for predicting variant type (SNP or indel), zygosity, alternative allele and indel length from aligned reads. For the well-characterized NA12878 human sample, Clairvoyante achieves 99.67, 95.78, 90.53\% F1-score on 1KP common variants, and 98.65, 92.57, 87.26\% F1-score for whole-genome analysis, using Illumina, PacBio, and Oxford Nanopore data, respectively. Training on a second human sample shows Clairvoyante is sample agnostic and finds variants in less than 2\,h on a standard server. Furthermore, we present 3,135 variants that are missed using Illumina but supported independently by both PacBio and Oxford Nanopore reads. Clairvoyante is available open-source ( https://github.com/aquaskyline/Clairvoyante ), with modules to train, utilize and visualize the model.},
langid = {english},
pmcid = {PMC6397153},
keywords = {Base Sequence,Computational Biology,DNA Mutational Analysis,Genome Human,Genome-Wide Association Study,Genomics,Genotype,Genotyping Techniques,Humans,INDEL Mutation,Nanopores,Neural Networks Computer,Polymorphism Single Nucleotide,Sequence Analysis DNA,Software}
}
@article{luPatternsFunctionalImplications2015,
title = {Patterns and Functional Implications of Rare Germline Variants across 12 Cancer Types},
author = {Lu, Charles and Xie, Mingchao and Wendl, Michael C. and Wang, Jiayin and McLellan, Michael D. and Leiserson, Mark D. M. and Huang, Kuan-lin and Wyczalkowski, Matthew A. and Jayasinghe, Reyka and Banerjee, Tapahsama and Ning, Jie and Tripathi, Piyush and Zhang, Qunyuan and Niu, Beifang and Ye, Kai and Schmidt, Heather K. and Fulton, Robert S. and McMichael, Joshua F. and Batra, Prag and Kandoth, Cyriac and Bharadwaj, Maheetha and Koboldt, Daniel C. and Miller, Christopher A. and Kanchi, Krishna L. and Eldred, James M. and Larson, David E. and Welch, John S. and You, Ming and Ozenberger, Bradley A. and Govindan, Ramaswamy and Walter, Matthew J. and Ellis, Matthew J. and Mardis, Elaine R. and Graubert, Timothy A. and Dipersio, John F. and Ley, Timothy J. and Wilson, Richard K. and Goodfellow, Paul J. and Raphael, Benjamin J. and Chen, Feng and Johnson, Kimberly J. and Parvin, Jeffrey D. and Ding, Li},
date = {2015-12-22},
journaltitle = {Nature Communications},
shortjournal = {Nat Commun},
volume = {6},
number = {1},
pages = {10086},
publisher = {Nature Publishing Group},
issn = {2041-1723},
doi = {10.1038/ncomms10086},
url = {https://www.nature.com/articles/ncomms10086},
urldate = {2022-05-19},
abstract = {Large-scale cancer sequencing data enable discovery of rare germline cancer susceptibility variants. Here we systematically analyse 4,034 cases from The Cancer Genome Atlas cancer cases representing 12 cancer types. We find that the frequency of rare germline truncations in 114 cancer-susceptibility-associated genes varies widely, from 4\% (acute myeloid leukaemia (AML)) to 19\% (ovarian cancer), with a notably high frequency of 11\% in stomach cancer. Burden testing identifies 13 cancer genes with significant enrichment of rare truncations, some associated with specific cancers (for example, RAD51C, PALB2 and MSH6 in AML, stomach and endometrial cancers, respectively). Significant, tumour-specific loss of heterozygosity occurs in nine genes (ATM, BAP1, BRCA1/2, BRIP1, FANCM, PALB2 and RAD51C/D). Moreover, our homology-directed repair assay of 68 BRCA1 rare missense variants supports the utility of allelic enrichment analysis for characterizing variants of unknown significance. The scale of this analysis and the somatic-germline integration enable the detection of rare variants that may affect individual susceptibility to tumour development, a critical step toward precision medicine.},
issue = {1},
langid = {english},
keywords = {Cancer genetics,Genetic variation}
}
@article{lyuRGelBLySFusion,
title = {The {{rGel}}/{{BLyS}} Fusion Toxin Inhibits {{STAT3}} Signaling via down-Regulation of Interleukin-6 Receptor in Diffuse Large {{B-cell}} Lymphoma},
author = {Lyu, Mi-Ae and Sung, Bokyung and Cheung, Lawrence H and Marks, John W and Aggarwal, Bharat B and Aguiar, Ricardo C T and Rosenblum, Michael G},
journaltitle = {Biochemical Pharmacology},
volume = {80},
number = {9},
pages = {1335--1342}
}
@article{machadoDiverseMutationalLandscapes2022,
title = {Diverse Mutational Landscapes in Human Lymphocytes},
author = {Machado, Heather E. and Mitchell, Emily and Øbro, Nina F. and Kübler, Kirsten and Davies, Megan and Leongamornlert, Daniel and Cull, Alyssa and Maura, Francesco and Sanders, Mathijs A. and Cagan, Alex T. J. and McDonald, Craig and Belmonte, Miriam and Shepherd, Mairi S. and Vieira Braga, Felipe A. and Osborne, Robert J. and Mahbubani, Krishnaa and Martincorena, Iñigo and Laurenti, Elisa and Green, Anthony R. and Getz, Gad and Polak, Paz and Saeb-Parsy, Kourosh and Hodson, Daniel J. and Kent, David G. and Campbell, Peter J.},
date = {2022-08},
journaltitle = {Nature},
shortjournal = {Nature},
volume = {608},
number = {7924},
eprint = {35948631},
eprinttype = {pmid},
pages = {724--732},
issn = {1476-4687},
doi = {10.1038/s41586-022-05072-7},
abstract = {The lymphocyte genome is prone to many threats, including programmed mutation during differentiation1, antigen-driven proliferation and residency in diverse microenvironments. Here, after developing protocols for expansion of single-cell lymphocyte cultures, we sequenced whole genomes from 717 normal naive and memory B and T cells and haematopoietic stem cells. All lymphocyte subsets carried more point mutations and structural variants than haematopoietic stem cells, with higher burdens in memory cells than in naive cells, and with T cells accumulating mutations at a higher rate throughout life. Off-target effects of immunological diversification accounted for approximately half of the additional differentiation-associated mutations in lymphocytes. Memory B cells acquired, on average, 18 off-target mutations genome-wide for every on-target IGHV mutation during the germinal centre reaction. Structural variation was 16-fold higher in lymphocytes than in stem cells, with around 15\% of deletions being attributable to off-target recombinase-activating gene activity. DNA damage from ultraviolet light exposure and other sporadic mutational processes generated hundreds to thousands of mutations in some memory cells. The mutation burden and signatures of normal B cells were broadly similar to those seen in many B-cell cancers, suggesting that malignant transformation of lymphocytes arises from the same mutational processes that are active across normal ontogeny. The mutational landscape of normal lymphocytes chronicles the off-target effects of programmed genome engineering during immunological diversification and the consequences of differentiation, proliferation and residency in diverse microenvironments.},
langid = {english},
pmcid = {PMC9402440},
keywords = {B-Lymphocytes,Cell Differentiation,Cell Proliferation,Cellular Microenvironment,DNA Damage,Germinal Center,Humans,Immunologic Memory,Lymphocytes,Mutation,Neoplasms}
}
@article{machadoEvolutionaryHistoryCopyNumberVariable2012,
title = {Evolutionary {{History}} of {{Copy-Number-Variable Locus}} for the {{Low-Affinity Fcγ Receptor}}: {{Mutation Rate}}, {{Autoimmune Disease}}, and the {{Legacy}} of {{Helminth Infection}}},
author = {Machado, Lee R. and Hardwick, Robert J. and Bowdrey, Jennifer and Bogle, Helen and Knowles, Timothy J. and Sironi, Manuela and Hollox, Edward J.},
date = {2012-12},
journaltitle = {The American Journal of Human Genetics},
volume = {90},
number = {6},
eprint = {22608500},
eprinttype = {pmid},
pages = {973--985},
issn = {0002-9297},
doi = {10.1016/j.ajhg.2012.04.018},
url = {http://dx.doi.org/10.1016/j.ajhg.2012.04.018},
abstract = {Both sequence variation and copy-number variation (CNV) of the genes encoding receptors for immunoglobulin G (Fcγ receptors) have been genetically and functionally associated with a number of autoimmune diseases. However, the molecular nature and evolutionary context of this variation is unknown. Here, we describe the structure of the CNV, estimate its mutation rate and diversity, and place it in the context of the known functional alloantigen variation of these genes. Deletion of Fcγ receptor IIIB, associated with systemic lupus erythematosus, is a result of independent nonallelic homologous recombination events with a frequency of approximately 0.1\%. We also show that pathogen diversity, in particular helminth diversity, has played a critical role in shaping the functional variation at these genes both between mammalian species and between human populations. Positively selected amino acids are involved in the interaction with IgG and include some amino acids that are known polymorphic alloantigens in humans. This supports a genetic contribution to the hygiene hypothesis, which states that past evolution in the context of helminth diversity has left humans with an array of susceptibility alleles for autoimmune disease in the context of a helminth-free environment. This approach shows the link between pathogens and autoimmune disease at the genetic level and provides a strategy for interrogating the genetic variation underlying autoimmune-disease risk and infectious-disease susceptibility.}
}
@article{maddocksIbrutinibBcellLymphomas2014,
title = {Ibrutinib in {{B-cell Lymphomas}}.},
author = {Maddocks, Kami and Blum, Kristie A},
date = {2014-06},
journaltitle = {Current treatment options in oncology},
volume = {15},
number = {2},
pages = {226--237}
}
@article{maddocksUpdateMantleCell2018,
title = {Update on Mantle Cell Lymphoma},
author = {Maddocks, Kami},
date = {2018-10-18},
journaltitle = {Blood},
shortjournal = {Blood},
volume = {132},
number = {16},
eprint = {30154113},
eprinttype = {pmid},
pages = {1647--1656},
issn = {1528-0020},
doi = {10.1182/blood-2018-03-791392},
abstract = {Mantle cell lymphoma (MCL) is a rare subtype of non-Hodgkin lymphoma that is most commonly treated with combination chemo-immunotherapy at diagnosis because of the poor prognosis. More indolent presentations have been described including patients who can defer initial therapy without adverse impact on survival. The 2016 World Health Organization updated classification describes 2 major subtypes, classical and leukemic nonnodal MCL, each with unique molecular features and clinical presentations. Although there is no standard of care for MCL, aggressive chemo-immunotherapy regimens containing rituximab and cytarabine, followed by consolidation with autologous stem cell transplantation and maintenance rituximab, are the most used approach in young fit patients, and chemo-immunotherapy, followed by rituximab maintenance, is most commonly used in older patients. Despite the improvement in response durations with currently available therapies, patients will inevitably relapse. A number of targeted therapies are approved in the relapsed setting and are now under evaluation in combination with standard frontline therapy. Although the approval of ibrutinib changed the landscape of therapy for relapsed MCL, prognosis remains poor after progression on ibrutinib supporting the development of ibrutinib combinations to prolong response duration as well as the development of other novel agents for ibrutinib refractory disease. With ibrutinib being incorporated into initial therapy regimens, new options will be needed at relapse. Prognostic markers, such as minimal residual disease, have been shown to correlate independently with outcomes along with predicting relapse, with the potential to guide therapeutic decisions. The future treatment of MCL therapy will need to incorporate therapy based on risk-stratification and nonchemotherapeutic approaches.},
langid = {english},
keywords = {Animals,Humans,Lymphoma Mantle-Cell,Prognosis}
}
@article{mahmoudSignificanceBcl2Bcl62011,
title = {Significance of {{Bcl-2}} and {{Bcl-6}} Immunostaining in {{B-Non Hodgkin}}'s Lymphoma},
author = {Mahmoud, Hanan Mohamed and El-Sakhawy, Yasmin Nabil},
date = {2011-11-16},
journaltitle = {Hematology Reports},
shortjournal = {Hematol Rep},
volume = {3},
number = {3},
eprint = {22593817},
eprinttype = {pmid},
pages = {e26},
issn = {2038-8322},
doi = {10.4081/hr.2011.e26},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3269794/},
urldate = {2022-10-04},
abstract = {The determination of prognosis for B-Non-Hodgkin's lymphoma (NHL) is known to be related to the multiple differences in tumor cell biology. Bcl-2 and Bcl-6 are two markers linked to germinal center B cells. Both markers are thought to have an effect on prognosis of mature B-cell neoplasms. Forty-four patients with chronic B-cell neoplasm were included; Bcl-2 and Bcl-6 expression by immunohistochemistry was examined. Bcl-2 protein was positive in 36.4\% (16 of 44) of cases (62.5\% of follicular lymphoma, 16.7\% of mantle cell lymphoma and 30\% of diffuse large B-cell lymphoma); the positive group implying a bad prognostic effect of the marker in NHL. Bcl-6 was positive in 13.6\% (6 of 44) of cases (11.1\% of mantle cell lymphoma and 40\% of diffuse large B-cell lymphoma) and its positivity implies a better disease course. Bcl-2 and Bcl-6 can be used as prognostic marker in NHL.},
pmcid = {PMC3269794}
}
@article{makhafolaApoptosisCancerCells2020,
title = {Apoptosis in {{Cancer Cells Is Induced}} by {{Alternative Splicing}} of {{hnRNPA2}}/{{B1 Through Splicing}} of {{Bcl-x}}, a {{Mechanism}} That {{Can Be Stimulated}} by an {{Extract}} of the {{South African Medicinal Plant}}, {{Cotyledon}} Orbiculata},
author = {Makhafola, Tshepiso Jan and Mbele, Mzwandile and Yacqub-Usman, Kiren and Hendren, Amy and Haigh, Daisy Belle and Blackley, Zoe and Meyer, Mervin and Mongan, Nigel Patrick and Bates, David Owen and Dlamini, Zodwa},
date = {2020-10-08},
journaltitle = {Frontiers in Oncology},
shortjournal = {Front. Oncol.},
volume = {10},
pages = {547392},
issn = {2234-943X},
doi = {10.3389/fonc.2020.547392},
url = {https://www.frontiersin.org/article/10.3389/fonc.2020.547392/full},
urldate = {2022-10-04},
langid = {english}
}
@article{makkiHistoneDeacetylaseInhibitor2016,
title = {Histone {{Deacetylase Inhibitor Vorinostat}} ({{SAHA}}, {{MK0683}}) {{Perturb miR-9-MCPIP1 Axis To Block IL-1β-induced IL-6 Expression}} in {{Human OA Chondrocytes}}},
author = {Makki, Mohammad S and Haqqi, Tariq M},
date = {2016-07},
journaltitle = {Connective Tissue Research},
pages = {03008207.2016.1211113--37}
}
@article{mandelbaumBLIMP1TumorSuppressor2010,
title = {{{BLIMP1}} Is a Tumor Suppressor Gene Frequently Disrupted in Activated {{B}} Cell-like Diffuse Large {{B}} Cell Lymphoma.},
author = {Mandelbaum, Jonathan and Bhagat, Govind and Tang, Hongyan and Mo, Tongwei and Brahmachary, Manisha and Shen, Qiong and Chadburn, Amy and Rajewsky, Klaus and Tarakhovsky, Alexander and Pasqualucci, Laura and Dalla-Favera, Riccardo},
date = {2010-12},
journaltitle = {Cancer Cell},
volume = {18},
number = {6},
pages = {568--579}
}
@article{mangLongNoncodingRNA2017,
title = {Long Noncoding {{RNA NEAT1}} Promotes Cell Proliferation and Invasion by Regulating {{hnRNP A2}} Expression in Hepatocellular Carcinoma Cells},
author = {Mang, Yuanyi and Li, Li and Ran, Jianghua and Zhang, Shengning and Liu, Jing and Li, Laibang and Chen, Yiming and Liu, Jian and Gao, Yang and Ren, Gang},
date = {2017-02-20},
journaltitle = {OncoTargets and Therapy},
shortjournal = {OTT},
volume = {10},
pages = {1003--1016},
publisher = {Dove Press},
doi = {10.2147/OTT.S116319},
url = {https://www.dovepress.com/long-noncoding-rna-neat1-promotes-cell-proliferation-and-invasion-by-r-peer-reviewed-fulltext-article-OTT},
urldate = {2022-09-28},
abstract = {Long noncoding RNA NEAT1 promotes cell proliferation and invasion by regulating hnRNP A2 expression in hepatocellular carcinoma cells Yuanyi Mang, Li Li, Jianghua Ran, Shengning Zhang, Jing Liu, Laibang Li, Yiming Chen, Jian Liu, Yang Gao, Gang Ren Department of Hepato-Biliary-Pancreatic Surgery, The Calmette Affiliated Hospital of Kunming Medical University, The First Hospital of Kunming, Kunming, Yunnan, People\’s Republic of China Abstract: Growing evidence demonstrates that long noncoding RNAs (lncRNAs) are involved in the progression of various cancers, including hepatocellular carcinoma (HCC). The role of nuclear-enriched abundant transcript 1 (NEAT1), an essential lncRNA for the formation of nuclear body paraspeckles, has not been fully explored in HCC. We aimed to determine the expression, roles and functional mechanisms of NEAT1 in the proliferation and invasion of HCC. Based on real-time polymerase chain reaction data, we suggest that NEAT1 is upregulated in HCC tissues compared with noncancerous liver tissues. The knockdown of NEAT1 altered global gene expression patterns and reduced HCC cell proliferation, invasion and migration. RNA immunoprecipitation and RNA pull-down assays confirmed that U2AF65 binds to NEAT1. Furthermore, the study indicated that NEAT1 regulated hnRNP A2 expression and that this regulation may be associated with the NEAT1\–U2AF65 protein complex. Thus, the NEAT1-hnRNP A2 regulation mechanism promotes HCC pathogenesis and may provide a potential target for the prognosis and treatment of HCC. Keywords: long noncoding RNA, NEAT1, RNA-binding protein, HCC},
langid = {english}
}
@article{mannenSam68NuclearBody2016,
title = {The {{Sam68}} Nuclear Body Is Composed of Two {{RNase-sensitive}} Substructures Joined by the Adaptor {{HNRNPL}}},
author = {Mannen, Taro and Yamashita, Seisuke and Tomita, Kozo and Goshima, Naoki and Hirose, Tetsuro},
date = {2016-07-04},
journaltitle = {Journal of Cell Biology},
shortjournal = {Journal of Cell Biology},
volume = {214},
number = {1},
pages = {45--59},
issn = {0021-9525},
doi = {10.1083/jcb.201601024},
url = {https://doi.org/10.1083/jcb.201601024},
urldate = {2023-01-09},
abstract = {The mammalian cell nucleus contains membraneless suborganelles referred to as nuclear bodies (NBs). Some NBs are formed with an architectural RNA (arcRNA) as the structural core. Here, we searched for new NBs that are built on unidentified arcRNAs by screening for ribonuclease (RNase)-sensitive NBs using 32,651 fluorescently tagged human cDNA clones. We identified 32 tagged proteins that required RNA for their localization in distinct nuclear foci. Among them, seven RNA-binding proteins commonly localized in the Sam68 nuclear body (SNB), which was disrupted by RNase treatment. Knockdown of each SNB protein revealed that SNBs are composed of two distinct RNase-sensitive substructures. One substructure is present as a distinct NB, termed the DBC1 body, in certain conditions, and the more dynamic substructure including Sam68 joins to form the intact SNB. HNRNPL acts as the adaptor to combine the two substructures and form the intact SNB through the interaction of two sets of RNA recognition motifs with the putative arcRNAs in the respective substructures.}
}
@article{mansouriFrequentNFKBIEDeletions2016,
title = {Frequent {{NFKBIE}} Deletions Are Associated with Poor Outcome in Primary Mediastinal {{B-cell}} Lymphoma},
author = {Mansouri, Larry and Noerenberg, Daniel and Young, Emma and Mylonas, Elena and Abdulla, Maysaa and Frick, Mareike and Asmar, Fazila and Ljungström, Viktor and Schneider, Markus and Yoshida, Kenichi and Skaftason, Aron and Pandzic, Tatjana and Gonzalez, Blanca and Tasidou, Anna and Waldhueter, Nils and Rivas-Delgado, Alfredo and Angelopoulou, Maria and Ziepert, Marita and Arends, Christopher Maximilian and Couronné, Lucile and Lenze, Dido and Baldus, Claudia D. and Bastard, Christian and Okosun, Jessica and Fitzgibbon, Jude and Dörken, Bernd and Drexler, Hans G. and Roos-Weil, Damien and Schmitt, Clemens A. and Munch-Petersen, Helga D. and Zenz, Thorsten and Hansmann, Martin-Leo and Strefford, Jonathan C. and Enblad, Gunilla and Bernard, Olivier A. and Ralfkiaer, Elisabeth and Erlanson, Martin and Korkolopoulou, Penelope and Hultdin, Magnus and Papadaki, Theodora and Grønbæk, Kirsten and Lopez-Guillermo, Armando and Ogawa, Seishi and Küppers, Ralf and Stamatopoulos, Kostas and Stavroyianni, Niki and Kanellis, George and Rosenwald, Andreas and Campo, Elias and Amini, Rose-Marie and Ott, German and Vassilakopoulos, Theodoros P. and Hummel, Michael and Rosenquist, Richard and Damm, Frederik},
date = {2016-12-08},
journaltitle = {Blood},
shortjournal = {Blood},
volume = {128},
number = {23},
pages = {2666--2670},
issn = {0006-4971},
doi = {10.1182/blood-2016-03-704528},
langid = {english}
}
@article{mareschalWholeExomeSequencing2016,
title = {Whole Exome Sequencing of Relapsed/Refractory Patients Expands the Repertoire of Somatic Mutations in Diffuse Large {{B-cell}} Lymphoma},
author = {Mareschal, Sylvain and Dubois, Sydney and Viailly, Pierre-Julien and Bertrand, Philippe and Bohers, Elodie and Maingonnat, Catherine and Jaïs, Jean-Philippe and Tesson, Bruno and Ruminy, Philippe and Peyrouze, Pauline and Copie-Bergman, Christiane and Fest, Thierry and Jo Molina, Thierry and Haioun, Corinne and Salles, Gilles and Tilly, Hervé and Lecroq, Thierry and Leroy, Karen and Jardin, Fabrice},
date = {2016-03},
journaltitle = {Genes, Chromosomes \& Cancer},
shortjournal = {Genes Chromosomes Cancer},
volume = {55},
number = {3},
eprint = {26608593},
eprinttype = {pmid},
pages = {251--267},
issn = {1098-2264},
doi = {10.1002/gcc.22328},
abstract = {Despite the many efforts already spent to enumerate somatic mutations in diffuse large B-cell lymphoma (DLBCL), previous whole-genome and whole-exome studies conducted on patients of mixed outcomes failed at characterizing the 30\% of patients who will relapse or resist current immunochemotherapies. To address this issue, we performed whole-exome sequencing of normal/tumoral DNA pairs in 14 relapsed/refractory (R/R) patients subclassified by full-transcriptome arrays (six activated B-cell like, three germinal center B-cell like, and five primary mediastinal B-cell lymphomas), from the LNH-03 LYSA clinical trial program. Aside from well-known DLBCL features, gene and pathway level recurrence analyses proposed several interesting leads including TBL1XR1 and activating mutations in IRF4 or in the insulin regulation pathway. Sequencing-based copy number analysis defined 23 short recurrently altered regions involving genes such as REL, CDKN2A, HYAL2, and TP53. Moreover, it highlighted mutations in genes such as GNA13, CARD11, MFHAS1, and PCLO as associated with secondary variant allele amplification events. The five primary mediastinal B-cell lymphomas (PMBL), while unexpected in a R/R cohort, showed a significantly higher mutation rate (P = 0.003) and provided many insights on this classical Hodgkin lymphoma related subtype. Novel genes such as XPO1, MFHAS1, and ITPKB were found particularly mutated, along with various cytokine-based signaling pathways. Among these analyses, somatic events in the NF-κB pathway were found preponderant in the three DLBCL subtypes, confirming its major implication in DLBCL aggressiveness and pinpointing several new candidate genes.},
langid = {english},
keywords = {Adult,Aged,Aged 80 and over,DNA Neoplasm,Exome,Female,High-Throughput Nucleotide Sequencing,Humans,Interferon Regulatory Factors,Lymphoma Large B-Cell Diffuse,Male,Middle Aged,Mutation,Neoplasm Recurrence Local,NF-kappa B,Signal Transduction}
}
@article{martinez-climentTransformationFollicularLymphoma2003,
title = {Transformation of Follicular Lymphoma to Diffuse Large Cell Lymphoma Is Associated with a Heterogeneous Set of {{DNA}} Copy Number and Gene Expression Alterations.},
author = {Martinez-Climent, Jose A and Alizadeh, Ash A and Segraves, Richard and Blesa, David and Rubio-Moscardo, Fanny and Albertson, Donna G and Garcia-Conde, Javier and Dyer, Martin J S and Levy, Ronald and Pinkel, Daniel and Lossos, Izidore S},
date = {2003-04},
journaltitle = {Blood},
volume = {101},
number = {8},
pages = {3109--3117}
}
@article{martinezProteinRNANetworksRegulated2016,
title = {Protein-{{RNA Networks Regulated}} by {{Normal}} and {{ALS-Associated Mutant HNRNPA2B1}} in the {{Nervous System}}},
author = {Martinez, Fernando J. and Pratt, Gabriel A. and Van Nostrand, Eric L. and Batra, Ranjan and Huelga, Stephanie C. and Kapeli, Katannya and Freese, Peter and Chun, Seung J. and Ling, Karen and Gelboin-Burkhart, Chelsea and Fijany, Layla and Wang, Harrison C. and Nussbacher, Julia K. and Broski, Sara M. and Kim, Hong Joo and Lardelli, Rea and Sundararaman, Balaji and Donohue, John P. and Javaherian, Ashkan and Lykke-Andersen, Jens and Finkbeiner, Steven and Bennett, C. Frank and Ares, Manuel and Burge, Christopher B. and Taylor, J. Paul and Rigo, Frank and Yeo, Gene W.},
date = {2016-11-23},
journaltitle = {Neuron},
shortjournal = {Neuron},
volume = {92},
number = {4},
pages = {780--795},
issn = {0896-6273},
doi = {10.1016/j.neuron.2016.09.050},
url = {http://www.sciencedirect.com/science/article/pii/S0896627316306559},
urldate = {2019-12-21},
abstract = {HnRNPA2B1 encodes an RNA binding protein associated with neurodegeneration. However, its function in the nervous system is unclear. Transcriptome-wide crosslinking and immunoprecipitation in mouse spinal cord discover UAGG motifs enriched within ∼2,500 hnRNP A2/B1 binding sites and an unexpected role for hnRNP A2/B1 in alternative polyadenylation. HnRNP A2/B1 loss results in alternative splicing (AS), including skipping of an exon in amyotrophic lateral sclerosis (ALS)-associated D-amino acid oxidase (DAO) that reduces D-serine metabolism. ALS-associated hnRNP A2/B1 D290V mutant patient fibroblasts and motor neurons differentiated from induced pluripotent stem cells (iPSC-MNs) demonstrate abnormal splicing changes, likely due to increased nuclear-insoluble hnRNP A2/B1. Mutant iPSC-MNs display decreased survival in long-term culture and exhibit hnRNP A2/B1 localization to cytoplasmic granules as well as exacerbated changes in gene expression and splicing upon cellular stress. Our findings provide a cellular resource and reveal RNA networks relevant to neurodegeneration, regulated by normal and mutant hnRNP A2/B1. Video Abstract},
langid = {english}
}
@article{maruyamaScreeningPosttranscriptionalRegulatory2016,
title = {Screening of Posttranscriptional Regulatory Molecules of {{I}}\κ{{B-}}\ζ},
author = {MaruYama, Takashi and Sayama, Aoi and Ishii, Ken J and Muta, Tatsushi},
date = {2016-01},
journaltitle = {Biochemical and biophysical research communications},
volume = {469},
number = {3},
pages = {711--715}
}
@article{marxTargetedProteomics2012,
title = {Targeted Proteomics},
author = {Marx, Vivien},
date = {2012-12},
journaltitle = {Nature Methods},
volume = {10},
number = {1},
eprint = {23547293},
eprinttype = {pmid},
pages = {nmeth.2285},
issn = {1548-7105},
doi = {10.1038/nmeth.2285},
url = {http://dx.doi.org/10.1038/nmeth.2285},
abstract = {{$<$}p{$>$}Analysis of a preselected group of proteins delivers more precise, quantitative, sensitive data to more biologists. Vivien Marx reports.{$<$}/p{$>$}}
}
@article{matthewsRegulationImmunoglobulinClassSwitch2014,
title = {Regulation of {{Immunoglobulin Class-Switch Recombination}}: {{Choreography}} of {{Noncoding Transcription}}, {{Targeted DNA Deamination}}, and {{Long-Range DNA Repair}}},
shorttitle = {Regulation of {{Immunoglobulin Class-Switch Recombination}}},
author = {Matthews, Allysia J. and Zheng, Simin and DiMenna, Lauren J. and Chaudhuri, Jayanta},
date = {2014},
journaltitle = {Advances in immunology},
shortjournal = {Adv Immunol},
volume = {122},
eprint = {24507154},
eprinttype = {pmid},
pages = {1--57},
issn = {0065-2776},
doi = {10.1016/B978-0-12-800267-4.00001-8},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4150736/},
urldate = {2023-12-18},
abstract = {Upon encountering antigens, mature IgM-positive B lymphocytes undergo class-switch recombination (CSR) wherein exons encoding the default Cμ constant coding gene segment of the immunoglobulin (Ig) heavy-chain (Igh) locus are excised and replaced with a new constant gene segment (referred to as “Ch genes”, e.g., Cγ, Cε, or Cα). The B cell thereby changes from expressing IgM to one producing IgG, IgE, or IgA, with each antibody isotype having a different effector function during an immune reaction. CSR is a DNA deletional-recombination reaction that proceeds through the generation of DNA double-strand breaks (DSBs) in repetitive switch (S) sequences preceding each Ch gene and is completed by end-joining between donor Sμ and acceptor S regions. CSR is a multistep reaction requiring transcription through S regions, the DNA cytidine deaminase AID, and the participation of several general DNA repair pathways including base excision repair, mismatch repair, and classical nonhomologous end-joining. In this review, we discuss our current understanding of how transcription through S regions generates substrates for AID-mediated deamination and how AID participates not only in the initiation of CSR but also in the conversion of deaminated residues into DSBs. Additionally, we review the multiple processes that regulate AID expression and facilitate its recruitment specifically to the Ig loci, and how deregulation of AID specificity leads to oncogenic translocations. Finally, we summarize recent data on the potential role of AID in the maintenance of the pluripotent stem cell state during epigenetic reprogramming.},
pmcid = {PMC4150736}
}
@article{maurerEventfreeSurvival242014,
title = {Event-Free Survival at 24 Months Is a Robust End Point for Disease-Related Outcome in Diffuse Large {{B-cell}} Lymphoma Treated with Immunochemotherapy},
author = {Maurer, Matthew J. and Ghesquières, Hervé and Jais, Jean-Philippe and Witzig, Thomas E. and Haioun, Corinne and Thompson, Carrie A. and Delarue, Richard and Micallef, Ivana N. and Peyrade, Frédéric and Macon, William R. and Jo Molina, Thierry and Ketterer, Nicolas and Syrbu, Sergei I. and Fitoussi, Olivier and Kurtin, Paul J. and Allmer, Cristine and Nicolas-Virelizier, Emmanuelle and Slager, Susan L. and Habermann, Thomas M. and Link, Brian K. and Salles, Gilles and Tilly, Hervé and Cerhan, James R.},
date = {2014-04-01},
journaltitle = {Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology},
shortjournal = {J Clin Oncol},
volume = {32},
number = {10},
eprint = {24550425},
eprinttype = {pmid},
pages = {1066--1073},
issn = {1527-7755},
doi = {10.1200/JCO.2013.51.5866},
abstract = {PURPOSE: Studies of diffuse large B-cell lymphoma (DLBCL) are typically evaluated by using a time-to-event approach with relapse, re-treatment, and death commonly used as the events. We evaluated the timing and type of events in newly diagnosed DLBCL and compared patient outcome with reference population data. PATIENTS AND METHODS: Patients with newly diagnosed DLBCL treated with immunochemotherapy were prospectively enrolled onto the University of Iowa/Mayo Clinic Specialized Program of Research Excellence Molecular Epidemiology Resource (MER) and the North Central Cancer Treatment Group NCCTG-N0489 clinical trial from 2002 to 2009. Patient outcomes were evaluated at diagnosis and in the subsets of patients achieving event-free status at 12 months (EFS12) and 24 months (EFS24) from diagnosis. Overall survival was compared with age- and sex-matched population data. Results were replicated in an external validation cohort from the Groupe d'Etude des Lymphomes de l'Adulte (GELA) Lymphome Non Hodgkinien 2003 (LNH2003) program and a registry based in Lyon, France. RESULTS: In all, 767 patients with newly diagnosed DLBCL who had a median age of 63 years were enrolled onto the MER and NCCTG studies. At a median follow-up of 60 months (range, 8 to 116 months), 299 patients had an event and 210 patients had died. Patients achieving EFS24 had an overall survival equivalent to that of the age- and sex-matched general population (standardized mortality ratio [SMR], 1.18; P = .25). This result was confirmed in 820 patients from the GELA study and registry in Lyon (SMR, 1.09; P = .71). Simulation studies showed that EFS24 has comparable power to continuous EFS when evaluating clinical trials in DLBCL. CONCLUSION: Patients with DLBCL who achieve EFS24 have a subsequent overall survival equivalent to that of the age- and sex-matched general population. EFS24 will be useful in patient counseling and should be considered as an end point for future studies of newly diagnosed DLBCL.},
langid = {english},
pmcid = {PMC3965261},
keywords = {Adolescent,Adult,Aged,Aged 80 and over,Antibodies Monoclonal Murine-Derived,Antineoplastic Combined Chemotherapy Protocols,Case-Control Studies,Clinical Trials as Topic,Disease-Free Survival,Female,Humans,Kaplan-Meier Estimate,Lymphoma Large B-Cell Diffuse,Male,Middle Aged,Recurrence,Rituximab,Time Factors,Young Adult}
}
@article{mcglincyExpressionProteomicsUPF12010,
title = {Expression Proteomics of {{UPF1}} Knockdown in {{HeLa}} Cells Reveals Autoregulation of {{hnRNP A2}}/{{B1}} Mediated by Alternative Splicing Resulting in Nonsense-Mediated {{mRNA}} Decay},
author = {McGlincy, Nicholas J. and Tan, Lit-Yeen and Paul, Nicodeme and Zavolan, Mihaela and Lilley, Kathryn S. and Smith, Christopher WJ},
date = {2010-10-14},
journaltitle = {BMC Genomics},
shortjournal = {BMC Genomics},
volume = {11},
number = {1},
pages = {565},
issn = {1471-2164},
doi = {10.1186/1471-2164-11-565},
url = {https://doi.org/10.1186/1471-2164-11-565},
urldate = {2022-09-28},
abstract = {In addition to acting as an RNA quality control pathway, nonsense-mediated mRNA decay (NMD) plays roles in regulating normal gene expression. In particular, the extent to which alternative splicing is coupled to NMD and the roles of NMD in regulating uORF containing transcripts have been a matter of debate.},
langid = {english},
keywords = {Exon Junction Complex,HeLa Cell,Napa,Protein Spot,Upstream Open Reading Frame}
}
@article{mckennaGenomeAnalysisToolkit2010,
title = {The {{Genome Analysis Toolkit}}: A {{MapReduce}} Framework for Analyzing next-Generation {{DNA}} Sequencing Data},
shorttitle = {The {{Genome Analysis Toolkit}}},
author = {McKenna, Aaron and Hanna, Matthew and Banks, Eric and Sivachenko, Andrey and Cibulskis, Kristian and Kernytsky, Andrew and Garimella, Kiran and Altshuler, David and Gabriel, Stacey and Daly, Mark and DePristo, Mark A.},
date = {2010-09},
journaltitle = {Genome Research},
shortjournal = {Genome Res.},
volume = {20},
number = {9},
eprint = {20644199},
eprinttype = {pmid},
pages = {1297--1303},
issn = {1549-5469},
doi = {10.1101/gr.107524.110},
abstract = {Next-generation DNA sequencing (NGS) projects, such as the 1000 Genomes Project, are already revolutionizing our understanding of genetic variation among individuals. However, the massive data sets generated by NGS--the 1000 Genome pilot alone includes nearly five terabases--make writing feature-rich, efficient, and robust analysis tools difficult for even computationally sophisticated individuals. Indeed, many professionals are limited in the scope and the ease with which they can answer scientific questions by the complexity of accessing and manipulating the data produced by these machines. Here, we discuss our Genome Analysis Toolkit (GATK), a structured programming framework designed to ease the development of efficient and robust analysis tools for next-generation DNA sequencers using the functional programming philosophy of MapReduce. The GATK provides a small but rich set of data access patterns that encompass the majority of analysis tool needs. Separating specific analysis calculations from common data management infrastructure enables us to optimize the GATK framework for correctness, stability, and CPU and memory efficiency and to enable distributed and shared memory parallelization. We highlight the capabilities of the GATK by describing the implementation and application of robust, scale-tolerant tools like coverage calculators and single nucleotide polymorphism (SNP) calling. We conclude that the GATK programming framework enables developers and analysts to quickly and easily write efficient and robust NGS tools, many of which have already been incorporated into large-scale sequencing projects like the 1000 Genomes Project and The Cancer Genome Atlas.},
langid = {english},
pmcid = {PMC2928508},
keywords = {Base Sequence,Genome,Genomics,Sequence Analysis DNA,Software}
}
@article{mclarenEnsemblVariantEffect2016,
title = {The {{Ensembl Variant Effect Predictor}}},
author = {McLaren, William and Gil, Laurent and Hunt, Sarah E. and Riat, Harpreet Singh and Ritchie, Graham R. S. and Thormann, Anja and Flicek, Paul and Cunningham, Fiona},
date = {2016-06-06},
journaltitle = {Genome Biology},
shortjournal = {Genome Biol.},
volume = {17},
number = {1},
eprint = {27268795},
eprinttype = {pmid},
pages = {122},
issn = {1474-760X},
doi = {10.1186/s13059-016-0974-4},
abstract = {The Ensembl Variant Effect Predictor is a powerful toolset for the analysis, annotation, and prioritization of genomic variants in coding and non-coding regions. It provides access to an extensive collection of genomic annotation, with a variety of interfaces to suit different requirements, and simple options for configuring and extending analysis. It is open source, free to use, and supports full reproducibility of results. The Ensembl Variant Effect Predictor can simplify and accelerate variant interpretation in a wide range of study designs.},
langid = {english},
pmcid = {PMC4893825},
keywords = {Computational Biology,Databases Nucleic Acid,Genetic Variation,Genome,Genomics,Humans,Internet,Molecular Sequence Annotation,NGS,SNP,Software,Variant annotation}
}
@online{MechanismsBcellLymphoma,
title = {Mechanisms of {{B-cell}} Lymphoma Pathogenesis - {{PubMed}}},
url = {https://pubmed.ncbi.nlm.nih.gov/15803153/},
urldate = {2024-03-25}
}
@article{meissnerE3UbiquitinLigase2013,
title = {The {{E3}} Ubiquitin Ligase {{UBR5}} Is Recurrently Mutated in Mantle Cell Lymphoma},
author = {Meissner, Barbara and Kridel, Robert and Lim, Raymond S. and Rogic, Sanja and Tse, Kane and Scott, David W. and Moore, Richard and Mungall, Andy J. and Marra, Marco A. and Connors, Joseph M. and Steidl, Christian and Gascoyne, Randy D.},
date = {2013-04-18},
journaltitle = {Blood},
shortjournal = {Blood},
volume = {121},
number = {16},
pages = {3161--3164},
issn = {0006-4971},
doi = {10.1182/blood-2013-01-478834},
url = {https://ashpublications.org/blood/article/121/16/3161/31598/The-E3-ubiquitin-ligase-UBR5-is-recurrently},
urldate = {2019-12-21},
langid = {english}
}
@article{mellorCriticalReviewRole2013,
title = {A Critical Review of the Role of {{Fc}} Gamma Receptor Polymorphisms in the Response to Monoclonal Antibodies in Cancer.},
author = {Mellor, James D and Brown, Michael P and Irving, Helen R and Zalcberg, John R and Dobrovic, Alexander},
date = {2013},
journaltitle = {Journal of hematology \& oncology},
volume = {6},
eprint = {23286345},
eprinttype = {pmid},
pages = {1},
issn = {1756-8722},
doi = {10.1186/1756-8722-6-1},
url = {http://dx.doi.org/10.1186/1756-8722-6-1},
abstract = {Antibody-dependent cellular cytotoxicity (ADCC) is a major mechanism of action of therapeutic monoclonal antibodies (mAbs) such as cetuximab, rituximab and trastuzumab. Fc gamma receptors (FcgR) on human white blood cells are an integral part of the ADCC pathway. Differential response to therapeutic mAbs has been reported to correlate with specific polymorphisms in two of these genes: FCGR2A (H131R) and FCGR3A (V158F). These polymorphisms are associated with differential affinity of the receptors for mAbs. This review critically examines the current evidence for genotyping the corresponding single nucleotide polymorphisms (SNPs) to predict response to mAbs in patients with cancer.}
}
@article{mendez-lagoMutationsMLL2MEF2B2010,
title = {Mutations {{In MLL2}} and {{MEF2B Genes In Follicular Lymphoma}} and {{Diffuse Large B-Cell Lymphoma}}},
author = {Mendez-Lago, M and Morin, R D and Mungall, A J},
date = {2010},
journaltitle = {Blood},
volume = {116},
pages = {473}
}
@article{mengSignalingdependentCoordinatedRegulation2007,
title = {Signaling-Dependent and Coordinated Regulation of Transcription, Splicing, and Translation Resides in a Single Coregulator, {{PCBP1}}},
author = {Meng, Qingchang and Rayala, Suresh K. and Gururaj, Anupama E. and Talukder, Amjad H. and O'Malley, Bert W. and Kumar, Rakesh},
date = {2007-04-03},
journaltitle = {Proceedings of the National Academy of Sciences of the United States of America},
shortjournal = {Proc Natl Acad Sci U S A},
volume = {104},
number = {14},
eprint = {17389360},
eprinttype = {pmid},
pages = {5866--5871},
issn = {0027-8424},
doi = {10.1073/pnas.0701065104},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1851583/},
urldate = {2022-09-28},
abstract = {Transcription, splicing, and translation are potentially coordinately regulatable in a temporospatial-dependent manner, although supporting experimental evidence for this notion is scarce. Yeast two-hybrid screening of a mammary gland cDNA library with human p21-activated kinase 1 (Pak1) as bait identified polyC-RNA-binding protein 1 (PCBP1), which controls translation from mRNAs containing the DICE (differentiation control element). Mitogenic stimulation of human cells phosphorylated PCBP1 on threonines 60 and 127 in a Pak1-sensitive manner. Pak1-dependent phosphorylation of PCBP1 released its binding and translational inhibition from a DICE-minigene. Overexpression of PCBP1 also inhibited the translation of the endogenous L1 cell adhesion molecule mRNA, which contains two DICE motifs in the 3′ untranslated region. We also found that Pak1 activation led to an increased nuclear retention of PCBP1, recruitment to the eukaryotic translation initiation factor 4E (eIF4E) promoter, and stimulation of eIF4E expression in a Pak1-sensitive manner. Moreover, mitogenic stimulation promoted Pak1- and PCBP1-dependent alternative splicing and exon inclusion from a CD44 minigene. The alternative splicing functions of PCBP1 were in turn mediated by its intrinsic interaction with Caper α, a U2 snRNP auxiliary factor-related protein previously implicated in RNA splicing. These findings establish the principle that a single coregulator can function as a signal-dependent and coordinated regulator of transcription, splicing, and translation.},
pmcid = {PMC1851583}
}
@article{meyerReflecting25Years2008,
title = {Reflecting on 25 Years with {{MYC}}},
author = {Meyer, Natalie and Penn, Linda Z.},
date = {2008-12},
journaltitle = {Nature Reviews Cancer},
shortjournal = {Nat Rev Cancer},
volume = {8},
number = {12},
pages = {976--990},
publisher = {Nature Publishing Group},
issn = {1474-1768},
doi = {10.1038/nrc2231},
url = {https://www.nature.com/articles/nrc2231},
urldate = {2022-10-06},
abstract = {MYC is an iconic oncogene that has been at the forefront of cancer research since its discovery. Looking back over the history of MYC research provides us with a framework with which to progress in the next 25 years, as outlined in this Timeline.},
issue = {12},
langid = {english},
keywords = {Biomedicine,Cancer Research,general}
}
@article{miaoTargetedDisruptionMCPIP12013,
title = {Targeted Disruption of {{MCPIP1}}\/{{Zc3h12a}} Results in Fatal Inflammatory Disease},
author = {Miao, Ruidong and Huang, Shengping and Zhou, Zhou and Quinn, Tim and Van Treeck, Benjamin and Nayyar, Tehreem and Dim, Daniel and Jiang, Zhisheng and Papasian, Christopher J and Chen, Y Eugene and Liu, Gang and Fu, Mingui},
date = {2013-04},
journaltitle = {Immunology and cell biology},
volume = {91},
number = {5},
pages = {368--376}
}
@article{michaelNuclearExportSignal1995,
title = {A Nuclear Export Signal in {{hnRNP A1}}: A Signal-Mediated, Temperature-Dependent Nuclear Protein Export Pathway},
shorttitle = {A Nuclear Export Signal in {{hnRNP A1}}},
author = {Michael, W. M. and Choi, M. and Dreyfuss, G.},
date = {1995-11-03},
journaltitle = {Cell},
shortjournal = {Cell},
volume = {83},
number = {3},
eprint = {8521471},
eprinttype = {pmid},
pages = {415--422},
issn = {0092-8674},
doi = {10.1016/0092-8674(95)90119-1},
abstract = {Pre-mRNAs are associated with hnRNPs, and these proteins play important roles in the biogenesis of mRNAs. The hnRNP A1 is one of the most abundant hnRNPs, and although localized primarily in the nucleoplasm, shuttles continuously between the nucleus and the cytoplasm. A 38 amino acid domain within A1, termed M9, which bears no resemblance to classical nuclear localization signal (NLS) sequences, localizes A1 to the nucleus. Here we show that M9 is also a nuclear export signal; placing M9 on a protein that is otherwise restricted to the nucleus, the nucleoplasmin core domain (NPc), efficiently exports it to the cytoplasm in a temperature-dependent manner. In contrast, classical NLSs cannot promote the export of NPc. These findings demonstrate that there is a signal-dependent, temperature-sensitive nuclear export pathway and strengthen the suggestion that A1 and other shuttling hnRNPs function as carriers for RNA during export to the cytoplasm.},
langid = {english},
keywords = {Amino Acid Sequence,Biological Transport,Cell Nucleus,HeLa Cells,Heterogeneous Nuclear Ribonucleoprotein A1,Heterogeneous-Nuclear Ribonucleoprotein Group A-B,Heterogeneous-Nuclear Ribonucleoproteins,Humans,Molecular Sequence Data,Nuclear Proteins,Protein Sorting Signals,Recombinant Proteins,Ribonucleoproteins,RNA Messenger,RNA-Binding Proteins,Temperature}
}
@article{michaelNuclearShuttlingDomain1997,
title = {The {{K}} Nuclear Shuttling Domain: A Novel Signal for Nuclear Import and Nuclear Export in the {{hnRNP K}} Protein.},
shorttitle = {The {{K}} Nuclear Shuttling Domain},
author = {Michael, W M and Eder, P S and Dreyfuss, G},
date = {1997-06-15},
journaltitle = {The EMBO Journal},
shortjournal = {EMBO J},
volume = {16},
number = {12},
eprint = {9218800},
eprinttype = {pmid},
pages = {3587--3598},
issn = {0261-4189},
doi = {10.1093/emboj/16.12.3587},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1169983/},
urldate = {2022-09-28},
abstract = {Protein import into the nucleus and export from the nucleus are signal-mediated processes that require energy. The nuclear transport process about which the most information is currently available is classical nuclear localization signal (NLS)-mediated nuclear import. However, details concerning the signal-mediated export of proteins and RNAs as well as alternative nuclear import pathways are beginning to emerge. An example of this is the heterogeneous nuclear ribonucleoprotein (hnRNP) A1 protein which, by virtue of its M9 domain, is actively exported from the nucleus and imported into the nucleus via a novel pathway mediated by the recently characterized transportin protein. Here we report that the shuttling hnRNP K protein contains a novel shuttling domain (termed KNS) which has many of the characteristics of M9, in that it confers bi-directional transport across the nuclear envelope. KNS-mediated nuclear import is dependent on RNA polymerase II transcription, and we show that a classical NLS can override this effect. Furthermore, KNS accesses a separate import pathway from either classical NLSs or M9. This demonstrates the existence of a third protein import pathway into the nucleus and thereby defines a new type of nuclear import/export signal.},
pmcid = {PMC1169983}
}
@article{michaelSignalSequencesThat1995,
title = {Signal Sequences That Target Nuclear Import and Nuclear Export of Pre-{{mRNA-binding}} Proteins},
author = {Michael, W. M. and Siomi, H. and Choi, M. and Piñol-Roma, S. and Nakielny, S. and Liu, Q. and Dreyfuss, G.},
date = {1995},
journaltitle = {Cold Spring Harbor Symposia on Quantitative Biology},
shortjournal = {Cold Spring Harb Symp Quant Biol},
volume = {60},
eprint = {8824440},
eprinttype = {pmid},
pages = {663--668},
issn = {0091-7451},
doi = {10.1101/sqb.1995.060.01.071},
langid = {english},
keywords = {Amino Acid Sequence,Animals,Biological Transport Active,Cell Nucleus,Cytoplasm,Fungal Proteins,HeLa Cells,Heterogeneous-Nuclear Ribonucleoproteins,Humans,Molecular Sequence Data,Protein Sorting Signals,Ribonucleoproteins,RNA Precursors,RNA-Binding Proteins,Saccharomyces cerevisiae,Sequence Homology Amino Acid,Signal Transduction}
}
@article{michelottiHeterogeneousNuclearRibonucleoprotein1996,
title = {Heterogeneous Nuclear Ribonucleoprotein {{K}} Is a Transcription Factor},
author = {Michelotti, E.F. and Michelotti, G.A. and Aronsohn, A.I. and Levens, D.},
date = {1996},
journaltitle = {Molecular and Cellular Biology},
volume = {16},
number = {5},
pages = {2350--2360},
issn = {0270-7306},
doi = {10.1128/MCB.16.5.2350},
abstract = {The CT element is a positively acting homopyrimidine tract upstream of the c-myc gene to which the well-characterized transcription factor Sp1 and heterogeneous nuclear ribonucleoprotein (hnRNP) K, a less well-characterized protein associated with hnRNP complexes, have previously been shown to bind. The present work demonstrates that both of these molecules contribute to CT element-activated transcription in vitro. The pyrimidine-rich strand of the CT element both bound to hnRNP K and competitively inhibited transcription in vitro, suggesting a role for hnRNP K in activating transcription through this single-stranded sequence. Direct addition of recombinant hnRNP K to reaction mixtures programmed with templates bearing single-stranded CT elements increased specific RNA synthesis. If hnRNP K is a transcription factor, then interactions with the RNA polymerase II transcription apparatus are predicted. Affinity columns charged with recombinant hnRNP K specifically bind a component(s) necessary for transcription activation. The depleted factors were biochemically complemented by a crude TFIID phosphocellulose fraction, indicating that hnRNP K might interact with the TATA-binding protein (TBP)-TBP-associated factor complex. Coimmunoprecipitation of a complex formed in vivo between hnRNP K and epitope-tagged TBP as well as binding in vitro between recombinant proteins demonstrated a protein-protein interaction between TBP and hnRNP K. Furthermore, when the two proteins were overexpressed in vivo, transcription from a CT element-dependent reporter was synergistically activated. These data indicate that hnRNP K binds to a specific cis element, interacts with the RNA polymerase II transcription machinery, and stimulates transcription and thus has all of the properties of a transcription factor.},
langid = {english}
}
@article{mihailovichMiR1792FinetunesMYC2015,
title = {{{miR-17-92}} Fine-Tunes {{MYC}} Expression and Function to Ensure Optimal {{B}} Cell Lymphoma Growth},
author = {Mihailovich, Marija and Bremang, Michael and Spadotto, Valeria and Musiani, Daniele and Vitale, Elena and Varano, Gabriele and Zambelli, Federico and Mancuso, Francesco M. and Cairns, David A. and Pavesi, Giulio and Casola, Stefano and Bonaldi, Tiziana},
date = {2015-11-10},
journaltitle = {Nature Communications},
shortjournal = {Nat Commun},
volume = {6},
eprint = {26555894},
eprinttype = {pmid},
pages = {8725},
issn = {2041-1723},
doi = {10.1038/ncomms9725},
abstract = {The synergism between c-MYC and miR-17-19b, a truncated version of the miR-17-92 cluster, is well-documented during tumor initiation. However, little is known about miR-17-19b function in established cancers. Here we investigate the role of miR-17-19b in c-MYC-driven lymphomas by integrating SILAC-based quantitative proteomics, transcriptomics and 3' untranslated region (UTR) analysis upon miR-17-19b overexpression. We identify over one hundred miR-17-19b targets, of which 40\% are co-regulated by c-MYC. Downregulation of a new miR-17/20 target, checkpoint kinase 2 (Chek2), increases the recruitment of HuR to c-MYC transcripts, resulting in the inhibition of c-MYC translation and thus interfering with in vivo tumor growth. Hence, in established lymphomas, miR-17-19b fine-tunes c-MYC activity through a tight control of its function and expression, ultimately ensuring cancer cell homeostasis. Our data highlight the plasticity of miRNA function, reflecting changes in the mRNA landscape and 3' UTR shortening at different stages of tumorigenesis.},
langid = {english},
pmcid = {PMC4667639},
keywords = {Animals,Cell Line Tumor,Checkpoint Kinase 2,Cloning Molecular,ELAV-Like Protein 1,Gene Expression Regulation Neoplastic,Lymphoma B-Cell,Mice,Mice Transgenic,MicroRNAs,Proteome,Proto-Oncogene Proteins c-myc}
}
@article{milosevicSubcellularFractionationTGFbeta1stimulated2009,
title = {Subcellular Fractionation of {{TGF-beta1-stimulated}} Lung Epithelial Cells: A Novel Proteomic Approach for Identifying Signaling Intermediates},
shorttitle = {Subcellular Fractionation of {{TGF-beta1-stimulated}} Lung Epithelial Cells},
author = {Milosevic, Jadranka and Bulau, Patrick and Mortz, Ejvind and Eickelberg, Oliver},
date = {2009-03},
journaltitle = {Proteomics},
shortjournal = {Proteomics},
volume = {9},
number = {5},
eprint = {19253281},
eprinttype = {pmid},
pages = {1230--1240},
issn = {1615-9861},
doi = {10.1002/pmic.200700604},
abstract = {Members of the transforming growth factor (TGF)-beta superfamily are key regulators of lung development and homeostasis, in particular by controlling alveolar/bronchial epithelial cell function. TGF-beta signaling involves ligand-dependent activation of receptor serine/threonine kinases, activation and subsequent nuclear translocation of pathway-specific transcription factors (Smads), and ultimately, modulation of gene expression. While Smad-dependent responses represent the primary signaling components activated by TGF-beta receptors, their function is controlled by a variety of cofactors. In addition, alternative signaling systems mediating TGF-beta-induced effects have recently been described such as MAP kinase pathways. To uncover novel proteins that participate in TGF-beta signaling via nuclear/cytoplasmic shuttling in lung epithelial cells, we have analyzed A549 human lung epithelial cells, using subcellular fractionation combined with 2-D PAGE, tryptic digestion, and MS. We identified a rapid increase in the cytosolic localization of KH-type splicing regulatory protein (KHSRP), far upstream element-binding protein (FUBP1), hnRNP-L, and hnRNP-H1, concomitant with a decrease in their nuclear localization in response to TGF-beta1. Proteomic data were confirmed by immunofluorescence and immunoblot analyses. In summary, we represent a powerful novel technology for the identification of previously unknown signaling intermediates.},
langid = {english},
keywords = {Cell Differentiation,Cell Line,Cell Nucleus,Cytosol,Electrophoresis Gel Two-Dimensional,Epithelial Cells,Humans,Lung,Proteome,Spectrometry Mass Matrix-Assisted Laser Desorption-Ionization,Subcellular Fractions,Transforming Growth Factor beta1}
}
@article{milpiedHumanGerminalCenter2018,
title = {Human Germinal Center Transcriptional Programs Are De-Synchronized in {{B}} Cell Lymphoma},
author = {Milpied, Pierre and Cervera-Marzal, Iñaki and Mollichella, Marie-Laure and Tesson, Bruno and Brisou, Gabriel and Traverse-Glehen, Alexandra and Salles, Gilles and Spinelli, Lionel and Nadel, Bertrand},
date = {2018-09},
journaltitle = {Nature Immunology},
volume = {19},
number = {9},
pages = {1013},
issn = {1529-2916},
doi = {10.1038/s41590-018-0181-4},
url = {https://www.nature.com/articles/s41590-018-0181-4},
urldate = {2019-07-08},
abstract = {Human follicular lymphomas arise from germinal center B cells. Milpied and colleagues use single-cell transcriptomic analysis to show that follicular lymphoma cells lose synchronized gene-expression patterns that characterize normal germinal center B cells.},
langid = {english}
}
@article{minoRegnase1RoquinRegulate2015,
title = {Regnase-1 and {{Roquin}} Regulate Inflammatory {{mRNAs}}.},
author = {Mino, Takashi and Takeuchi, Osamu},
date = {2015-07},
journaltitle = {Oncotarget},
volume = {6},
number = {20},
pages = {17869--17870}
}
@article{minoRegnase1RoquinRegulate2015a,
title = {Regnase-1 and {{Roquin Regulate}} a {{Common Element}} in {{Inflammatory mRNAs}} by {{Spatiotemporally Distinct Mechanisms}}.},
author = {Mino, Takashi and Murakawa, Yasuhiro and Fukao, Akira and Vandenbon, Alexis and Wessels, Hans-Hermann and Ori, Daisuke and Uehata, Takuya and Tartey, Sarang and Akira, Shizuo and Suzuki, Yutaka and Vinuesa, Carola G and Ohler, Uwe and Standley, Daron M and Landthaler, Markus and Fujiwara, Toshinobu and Takeuchi, Osamu},
date = {2015-05},
journaltitle = {Cell},
volume = {161},
number = {5},
pages = {1058--1073}
}
@article{modianoDistinctBCellTCell2005,
title = {Distinct {{B-Cell}} and {{T-Cell Lymphoproliferative Disease Prevalence}} among {{Dog Breeds Indicates Heritable Risk}}},
author = {Modiano, Jaime F. and Breen, Matthew and Burnett, Robert C. and Parker, Heidi G. and Inusah, Seidu and Thomas, Rachael and Avery, Paul R. and Lindblad-Toh, Kerstin and Ostrander, Elaine A. and Cutter, Gary C. and Avery, Anne C.},
date = {2005-07-01},
journaltitle = {Cancer Research},
shortjournal = {Cancer Res},
volume = {65},
number = {13},
eprint = {15994938},
eprinttype = {pmid},
pages = {5654--5661},
publisher = {American Association for Cancer Research},
issn = {0008-5472, 1538-7445},
doi = {10.1158/0008-5472.CAN-04-4613},
url = {https://cancerres.aacrjournals.org/content/65/13/5654},
urldate = {2021-05-13},
abstract = {Immunophenotypes in lymphoproliferative diseases (LPD) are prognostically significant, yet causative factors for these conditions, and specifically those associated with heritable risk, remain elusive. The full spectrum of LPD seen in humans occurs in dogs, but the incidence and lifetime risk of naturally occurring LPD differs among dog breeds. Taking advantage of the limited genetic heterogeneity that exists within dog breeds, we tested the hypothesis that the prevalence of LPD immunophenotypes would differ among different breeds. The sample population included 1,263 dogs representing 87 breeds. Immunophenotype was determined by the presence of clonal rearrangements of immunoglobulin heavy chain or T-cell receptor γ chain. The probability of observing the number of B-cell or T-cell tumors in a particular breed or breed group was compared with three reference populations. Significance was computed using χ2 test, and logistic regression was used to confirm binomial predictions. The data show that, among 87 breeds tested, 15 showed significant differences from the prevalence of LPD immunophenotypes seen across the dog population as a whole. More significantly, elevated risk for T-cell LPD seems to have arisen ancestrally and is retained in related breed groups, whereas increased risk for B-cell disease may stem from different risk factors, or combinations of risk factors, arising during the process of breed derivation and selection. The data show that domestic dogs provide a unique and valuable resource to define factors that mediate risk as well as genes involved in the initiation of B-cell and T-cell LPD.},
langid = {english}
}
@article{mohantyCCND1MutationsIncrease2016,
title = {{{CCND1}} Mutations Increase Protein Stability and Promote Ibrutinib Resistance in Mantle Cell Lymphoma},
author = {Mohanty, Atish and Sandoval, Natalie and Das, Manasi and Pillai, Raju and Chen, Lu and Chen, Robert W. and Amin, Hesham M. and Wang, Michael and Marcucci, Guido and Weisenburger, Dennis D. and Rosen, Steven T. and Pham, Lan V. and Ngo, Vu N.},
date = {2016-10-04},
journaltitle = {Oncotarget},
volume = {7},
number = {45},
pages = {73558--73572},
issn = {1949-2553},
doi = {10.18632/oncotarget.12434},
url = {http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=12434&pubmed-linkout=1},
urldate = {2019-12-21},
abstract = {Oncotarget | https://doi.org/10.18632/oncotarget.12434 Atish Mohanty, Natalie Sandoval, Manasi Das, Raju Pillai, Lu Chen, Robert W. Chen, Hesham M. Amin, Michael Wang, Guido Marcucci, Dennis D. Weisenburger,...}
}
@article{mondalFunctionalRequirementsAID2016,
title = {Functional Requirements of {{AID}}’s Higher Order Structures and Their Interaction with {{RNA-binding}} Proteins},
author = {Mondal, Samiran and Begum, Nasim A. and Hu, Wenjun and Honjo, Tasuku},
date = {2016-03-15},
journaltitle = {Proceedings of the National Academy of Sciences},
volume = {113},
number = {11},
pages = {E1545-E1554},
publisher = {Proceedings of the National Academy of Sciences},
doi = {10.1073/pnas.1601678113},
url = {https://www.pnas.org/doi/full/10.1073/pnas.1601678113},
urldate = {2022-10-04}
}
@article{montiIntegrativeAnalysisReveals2012,
title = {Integrative {{Analysis Reveals}} an {{Outcome-Associated}} and {{Targetable Pattern}} of P53 and {{Cell Cycle Deregulation}} in {{Diffuse Large B Cell Lymphoma}}},
author = {Monti, Stefano and Chapuy, Bjoern and Takeyama, Kunihiko and Rodig, Scott~J. and Hao, Yansheng and Yeda, Kelly~T. and Inguilizian, Haig and Mermel, Craig and Currie, Treeve and Dogan, Ahmet and Kutok, Jeffery~L. and Beroukhim, Rameen and Neuberg, Donna and Habermann, Thomas~M. and Getz, Gad and Kung, Andrew~L. and Golub, Todd~R. and Shipp, Margaret~A.},
date = {2012-09-11},
journaltitle = {Cancer Cell},
shortjournal = {Cancer Cell},
volume = {22},
number = {3},
pages = {359--372},
issn = {1535-6108},
doi = {10.1016/j.ccr.2012.07.014},
url = {http://www.sciencedirect.com/science/article/pii/S1535610812003066},
urldate = {2019-07-08},
abstract = {Summary Diffuse large B cell lymphoma (DLBCL) is a clinically and biologically heterogeneous disease with a high proliferation rate. By integrating copy number data with transcriptional profiles and performing pathway analysis in primary DLBCLs, we identified a comprehensive set of copy number alterations (CNAs) that decreased p53 activity and perturbed cell cycle regulation. Primary tumors either had multiple complementary alterations of p53 and cell cycle components or largely lacked these lesions. DLBCLs with p53 and cell cycle pathway CNAs had decreased abundance of p53 target transcripts and increased expression of E2F target genes and the Ki67 proliferation marker. CNAs of the CDKN2A-TP53-RB-E2F axis provide a structural basis for increased proliferation in DLBCL, predict outcome with current therapy, and suggest targeted treatment approaches.}
}
@article{montiMolecularProfilingDiffuse2005,
title = {Molecular Profiling of Diffuse Large {{B-cell}} Lymphoma Identifies Robust Subtypes Including One Characterized by Host Inflammatory Response},
author = {Monti, S},
date = {2005-03},
journaltitle = {Blood},
volume = {105},
number = {5},
pages = {1851--1861}
}
@article{monzon-casanovaRNABindingProtein2018,
title = {The {{RNA}} Binding Protein {{PTBP1}} Is Necessary for {{B}} Cell Selection in Germinal Centers},
author = {Monzón-Casanova, Elisa and Screen, Michael and Díaz-Muñoz, Manuel D. and Coulson, Richard M. R. and Bell, Sarah E. and Lamers, Greta and Solimena, Michele and Smith, Christopher W.J. and Turner, Martin},
date = {2018-03},
journaltitle = {Nature immunology},
shortjournal = {Nat Immunol},
volume = {19},
number = {3},
eprint = {29358707},
eprinttype = {pmid},
pages = {267--278},
issn = {1529-2908},
doi = {10.1038/s41590-017-0035-5},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5842895/},
urldate = {2022-10-06},
abstract = {Antibody affinity maturation occurs in germinal centres (GC) where B cells cycle between the light zone (LZ) and the dark zone. In the LZ GC B cells bearing immunoglobulins with the highest affinity for antigen receive positive selection signals from T helper cells that promotes their rapid proliferation. Here we show that the RNA binding protein PTBP1 is necessary for the progression of GC B cells through late S-phase of the cell cycle and for affinity maturation. PTBP1 is required for the proper expression of the c-MYC-dependent gene program induced in GC B cells receiving T cell help and directly regulates the alternative splicing and abundance of transcripts increased during positive selection to promote proliferation.},
pmcid = {PMC5842895}
}
@article{moreiraUpstreamSequenceElement1998,
title = {The Upstream Sequence Element of the {{C2}} Complement Poly({{A}}) Signal Activates {{mRNA}} 3′ End Formation by Two Distinct Mechanisms},
author = {Moreira, Alexandra and Takagaki, Yoshio and Brackenridge, Simon and Wollerton, Matthew and Manley, James L. and Proudfoot, Nicholas J.},
date = {1998-08-15},
journaltitle = {Genes \& Development},
shortjournal = {Genes Dev.},
volume = {12},
number = {16},
pages = {2522--2534},
publisher = {Cold Spring Harbor Lab},
issn = {0890-9369, 1549-5477},
doi = {10.1101/gad.12.16.2522},
url = {http://genesdev.cshlp.org/content/12/16/2522},
urldate = {2022-09-27},
abstract = {The poly(A) signal of the C2 complement gene is unusual in that it possesses an upstream sequence element (USE) required for full activity in vivo. We describe here in vitro experiments demonstrating that this USE enhances both the cleavage and poly(A) addition reactions. We also show that the C2 USE can be cross-linked efficiently to a 55-kD protein that we identify as the polypyrimidine tract-binding protein (PTB), implicated previously in modulation of pre-mRNA splicing. Mutation of the PTB-binding site significantly reduces the efficiency of the C2 poly(A) site both in vivo and in vitro. Furthermore, addition of PTB to reconstituted processing reactions enhances cleavage at the C2 poly(A) site, indicating that PTB has a direct role in recognition of this signal. The C2 USE, however, also increases the affinity of general polyadenylation factors independently for the C2 poly(A) signal as detected by enhanced binding of cleavage-stimulaton factor (CstF). Strikingly, this leads to a novel CstF-dependant enhancement of the poly(A) synthesis phase of the reaction. These studies both emphasize the interconnection between splicing and polyadenylation and indicate an unexpected flexibility in the organization of mammalian poly(A) sites.},
langid = {english},
keywords = {C2 complement gene,cleavage and polyadenylation,poly(A) signal,PTB,upstream sequence element}
}
@article{morinFrequentMutationHistonemodifying2011,
title = {Frequent Mutation of Histone-Modifying Genes in Non-{{Hodgkin}} Lymphoma},
author = {Morin, Ryan D. and Mendez-Lago, Maria and Mungall, Andrew J. and Goya, Rodrigo and Mungall, Karen L. and Corbett, Richard D. and Johnson, Nathalie A. and Severson, Tesa M. and Chiu, Readman and Field, Matthew and Jackman, Shaun and Krzywinski, Martin and Scott, David W. and Trinh, Diane L. and Tamura-Wells, Jessica and Li, Sa and Firme, Marlo R. and Rogic, Sanja and Griffith, Malachi and Chan, Susanna and Yakovenko, Oleksandr and Meyer, Irmtraud M. and Zhao, Eric Y. and Smailus, Duane and Moksa, Michelle and Chittaranjan, Suganthi and Rimsza, Lisa and Brooks-Wilson, Angela and Spinelli, John J. and Ben-Neriah, Susana and Meissner, Barbara and Woolcock, Bruce and Boyle, Merrill and McDonald, Helen and Tam, Angela and Zhao, Yongjun and Delaney, Allen and Zeng, Thomas and Tse, Kane and Butterfield, Yaron and Birol, Inanç and Holt, Rob and Schein, Jacqueline and Horsman, Douglas E. and Moore, Richard and Jones, Steven J. M. and Connors, Joseph M. and Hirst, Martin and Gascoyne, Randy D. and Marra, Marco A.},
date = {2011-07-27},
journaltitle = {Nature},
shortjournal = {Nature},
volume = {476},
number = {7360},
eprint = {21796119},
eprinttype = {pmid},
pages = {298--303},
issn = {1476-4687},
doi = {10.1038/nature10351},
abstract = {Follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) are the two most common non-Hodgkin lymphomas (NHLs). Here we sequenced tumour and matched normal DNA from 13 DLBCL cases and one FL case to identify genes with mutations in B-cell NHL. We analysed RNA-seq data from these and another 113 NHLs to identify genes with candidate mutations, and then re-sequenced tumour and matched normal DNA from these cases to confirm 109 genes with multiple somatic mutations. Genes with roles in histone modification were frequent targets of somatic mutation. For example, 32\% of DLBCL and 89\% of FL cases had somatic mutations in MLL2, which encodes a histone methyltransferase, and 11.4\% and 13.4\% of DLBCL and FL cases, respectively, had mutations in MEF2B, a calcium-regulated gene that cooperates with CREBBP and EP300 in acetylating histones. Our analysis suggests a previously unappreciated disruption of chromatin biology in lymphomagenesis.},
langid = {english},
pmcid = {PMC3210554},
keywords = {Chromatin,DNA-Binding Proteins,Genome Human,Histone Acetyltransferases,Histone Methyltransferases,Histone-Lysine N-Methyltransferase,Histones,Humans,Loss of Heterozygosity,Lymphoma Follicular,Lymphoma Large B-Cell Diffuse,Lymphoma Non-Hodgkin,MADS Domain Proteins,MEF2 Transcription Factors,Mutation,Myogenic Regulatory Factors,Neoplasm Proteins}
}
@article{morinGeneticLandscapesRelapsed2016,
title = {Genetic {{Landscapes}} of {{Relapsed}} and {{Refractory Diffuse Large B-Cell Lymphomas}}},
author = {Morin, Ryan D. and Assouline, Sarit and Alcaide, Miguel and Mohajeri, Arezoo and Johnston, Rebecca L. and Chong, Lauren and Grewal, Jasleen and Yu, Stephen and Fornika, Daniel and Bushell, Kevin and Nielsen, Torsten Holm and Petrogiannis-Haliotis, Tina and Crump, Michael and Tosikyan, Axel and Grande, Bruno M. and MacDonald, David and Rousseau, Caroline and Bayat, Maryam and Sesques, Pierre and Froment, Remi and Albuquerque, Marco and Monczak, Yury and Oros, Kathleen Klein and Greenwood, Celia and Riazalhosseini, Yasser and Arseneault, Madeleine and Camlioglu, Errol and Constantin, André and Pan-Hammarstrom, Qiang and Peng, Roujun and Mann, Koren K. and Johnson, Nathalie A.},
date = {2016-05-01},
journaltitle = {Clinical Cancer Research: An Official Journal of the American Association for Cancer Research},
shortjournal = {Clin Cancer Res},
volume = {22},
number = {9},
eprint = {26647218},
eprinttype = {pmid},
pages = {2290--2300},
issn = {1557-3265},
doi = {10.1158/1078-0432.CCR-15-2123},
abstract = {PURPOSE: Relapsed or refractory diffuse large B-cell lymphoma (rrDLBCL) is fatal in 90\% of patients, and yet little is known about its biology. EXPERIMENTAL DESIGN: Using exome sequencing, we characterized the mutation profiles of 38 rrDLBCL biopsies obtained at the time of progression after immunochemotherapy. To identify genes that may be associated with relapse, we compared the mutation frequency in samples obtained at relapse to an unrelated cohort of 138 diagnostic DLBCLs and separately amplified specific mutations in their matched diagnostic samples to identify clonal expansions. RESULTS: On the basis of a higher frequency at relapse and evidence for clonal selection, TP53, FOXO1, MLL3 (KMT2C), CCND3, NFKBIZ, and STAT6 emerged as top candidate genes implicated in therapeutic resistance. We observed individual examples of clonal expansions affecting genes whose mutations had not been previously associated with DLBCL including two regulators of NF-κB: NFKBIE and NFKBIZ We detected mutations that may be affect sensitivity to novel therapeutics, such as MYD88 and CD79B mutations, in 31\% and 23\% of patients with activated B-cell-type of rrDLBCL, respectively. We also identified recurrent STAT6 mutations affecting D419 in 36\% of patients with the germinal center B (GCB) cell rrDLBCL. These were associated with activated JAK/STAT signaling, increased phospho-STAT6 protein expression and increased expression of STAT6 target genes. CONCLUSIONS: This work improves our understanding of therapeutic resistance in rrDLBCL and has identified novel therapeutic opportunities especially for the high-risk patients with GCB-type rrDLBCL. Clin Cancer Res; 22(9); 2290-300. ©2015 AACR.},
langid = {english},
keywords = {Adult,Aged,B-Lymphocytes,CD79 Antigens,Cyclin D3,Female,Forkhead Box Protein O1,Gene Expression Regulation Neoplastic,Germinal Center,Humans,Janus Kinases,Lymphoma Large B-Cell Diffuse,Male,Middle Aged,Morinlab,Mutation,Myeloid Differentiation Factor 88,Myeloid-Lymphoid Leukemia Protein,Neoplasm Recurrence Local,NF-kappa B,Nuclear Proteins,Prospective Studies,Signal Transduction,STAT6 Transcription Factor,Tumor Suppressor Protein p53}
}
@article{morinMolecularProfilingDiffuse2022,
title = {Molecular Profiling in Diffuse Large {{B-cell}} Lymphoma: Why so Many Types of Subtypes?},
shorttitle = {Molecular Profiling in Diffuse Large {{B-cell}} Lymphoma},
author = {Morin, Ryan D. and Arthur, Sarah E. and Hodson, Daniel J.},
date = {2022-02},
journaltitle = {British Journal of Haematology},
shortjournal = {Br J Haematol},
volume = {196},
number = {4},
eprint = {34467527},
eprinttype = {pmid},
pages = {814--829},
issn = {1365-2141},
doi = {10.1111/bjh.17811},
abstract = {The term diffuse large B-cell lymphoma (DLBCL) includes a heterogeneous collection of biologically distinct tumours. This heterogeneity currently presents a barrier to the successful deployment of novel, biologically targeted therapies. Molecular profiling studies have recently proposed new molecular classification systems. These have the potential to resolve the biological heterogeneity of DLBCL into manageable subgroups of tumours that rely on shared oncogenic programmes. In many cases these biological programmes straddle the boundaries of our existing systems for classifying B-cell lymphomas. Here we review the findings from these major molecular profiling studies with a specific focus on those that propose new genetic subgroups of DLBCL. We highlight the areas of consensus and discordance between these studies and discuss the implications for current clinical practice and for clinical trials. Finally, we address the outstanding challenges and solutions to the introduction of genomic subtyping and precision medicine in DLBCL.},
langid = {english},
keywords = {cancer genetics,classifications,diffuse large B-cell lymphoma,Gene Expression Profiling,Genomics,Humans,Lymphoma Large B-Cell Diffuse,lymphomas,Morinlab,mutation analysis,Prognosis}
}
@article{morinMutationalStructuralAnalysis2013,
title = {Mutational and Structural Analysis of Diffuse Large {{B-cell}} Lymphoma Using Whole-Genome Sequencing},
author = {Morin, Ryan D. and Mungall, Karen and Pleasance, Erin and Mungall, Andrew J. and Goya, Rodrigo and Huff, Ryan D. and Scott, David W. and Ding, Jiarui and Roth, Andrew and Chiu, Readman and Corbett, Richard D. and Chan, Fong Chun and Mendez-Lago, Maria and Trinh, Diane L. and Bolger-Munro, Madison and Taylor, Greg and Hadj Khodabakhshi, Alireza and Ben-Neriah, Susana and Pon, Julia and Meissner, Barbara and Woolcock, Bruce and Farnoud, Noushin and Rogic, Sanja and Lim, Emilia L. and Johnson, Nathalie A. and Shah, Sohrab and Jones, Steven and Steidl, Christian and Holt, Robert and Birol, Inanc and Moore, Richard and Connors, Joseph M. and Gascoyne, Randy D. and Marra, Marco A.},
date = {2013-08-15},
journaltitle = {Blood},
shortjournal = {Blood},
volume = {122},
number = {7},
eprint = {23699601},
eprinttype = {pmid},
pages = {1256--1265},
issn = {1528-0020},
doi = {10.1182/blood-2013-02-483727},
abstract = {Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous cancer composed of at least 2 molecular subtypes that differ in gene expression and distribution of mutations. Recently, application of genome/exome sequencing and RNA-seq to DLBCL has revealed numerous genes that are recurrent targets of somatic point mutation in this disease. Here we provide a whole-genome-sequencing-based perspective of DLBCL mutational complexity by characterizing 40 de novo DLBCL cases and 13 DLBCL cell lines and combining these data with DNA copy number analysis and RNA-seq from an extended cohort of 96 cases. Our analysis identified widespread genomic rearrangements including evidence for chromothripsis as well as the presence of known and novel fusion transcripts. We uncovered new gene targets of recurrent somatic point mutations and genes that are targeted by focal somatic deletions in this disease. We highlight the recurrence of germinal center B-cell-restricted mutations affecting genes that encode the S1P receptor and 2 small GTPases (GNA13 and GNAI2) that together converge on regulation of B-cell homing. We further analyzed our data to approximate the relative temporal order in which some recurrent mutations were acquired and demonstrate that ongoing acquisition of mutations and intratumoral clonal heterogeneity are common features of DLBCL. This study further improves our understanding of the processes and pathways involved in lymphomagenesis, and some of the pathways mutated here may indicate new avenues for therapeutic intervention.},
langid = {english},
pmcid = {PMC3744992},
keywords = {Biomarkers Tumor,DNA Copy Number Variations,Gene Expression Profiling,Genome Human,GTP-Binding Protein alpha Subunits G12-G13,High-Throughput Nucleotide Sequencing,Humans,Lymphoma Large B-Cell Diffuse,Mutation,Oligonucleotide Array Sequence Analysis,Real-Time Polymerase Chain Reaction,Reverse Transcriptase Polymerase Chain Reaction,RNA Messenger,Tumor Cells Cultured}
}
@article{morinSomaticMutationsAltering2010,
title = {Somatic Mutations Altering {{EZH2}} ({{Tyr641}}) in Follicular and Diffuse Large {{B-cell}} Lymphomas of Germinal-Center Origin},
author = {Morin, Ryan D. and Johnson, Nathalie A. and Severson, Tesa M. and Mungall, Andrew J. and An, Jianghong and Goya, Rodrigo and Paul, Jessica E. and Boyle, Merrill and Woolcock, Bruce W. and Kuchenbauer, Florian and Yap, Damian and Humphries, R. Keith and Griffith, Obi L. and Shah, Sohrab and Zhu, Henry and Kimbara, Michelle and Shashkin, Pavel and Charlot, Jean F. and Tcherpakov, Marianna and Corbett, Richard and Tam, Angela and Varhol, Richard and Smailus, Duane and Moksa, Michelle and Zhao, Yongjun and Delaney, Allen and Qian, Hong and Birol, Inanc and Schein, Jacqueline and Moore, Richard and Holt, Robert and Horsman, Doug E. and Connors, Joseph M. and Jones, Steven and Aparicio, Samuel and Hirst, Martin and Gascoyne, Randy D. and Marra, Marco A.},
date = {2010-02},
journaltitle = {Nature Genetics},
shortjournal = {Nat Genet},
volume = {42},
number = {2},
eprint = {20081860},
eprinttype = {pmid},
pages = {181--185},
issn = {1546-1718},
doi = {10.1038/ng.518},
abstract = {Follicular lymphoma (FL) and the GCB subtype of diffuse large B-cell lymphoma (DLBCL) derive from germinal center B cells. Targeted resequencing studies have revealed mutations in various genes encoding proteins in the NF-kappaB pathway that contribute to the activated B-cell (ABC) DLBCL subtype, but thus far few GCB-specific mutations have been identified. Here we report recurrent somatic mutations affecting the polycomb-group oncogene EZH2, which encodes a histone methyltransferase responsible for trimethylating Lys27 of histone H3 (H3K27). After the recent discovery of mutations in KDM6A (UTX), which encodes the histone H3K27me3 demethylase UTX, in several cancer types, EZH2 is the second histone methyltransferase gene found to be mutated in cancer. These mutations, which result in the replacement of a single tyrosine in the SET domain of the EZH2 protein (Tyr641), occur in 21.7\% of GCB DLBCLs and 7.2\% of FLs and are absent from ABC DLBCLs. Our data are consistent with the notion that EZH2 proteins with mutant Tyr641 have reduced enzymatic activity in vitro.},
langid = {english},
pmcid = {PMC2850970},
keywords = {Adult,Aged,Amino Acid Sequence,Base Sequence,DNA Mutational Analysis,DNA-Binding Proteins,Enhancer of Zeste Homolog 2 Protein,Exons,Female,Gene Expression Profiling,Gene Expression Regulation Neoplastic,Genome Human,Germinal Center,Humans,Lymphoma Follicular,Lymphoma Large B-Cell Diffuse,Male,Middle Aged,Molecular Sequence Data,Mutant Proteins,Mutation,Polycomb Repressive Complex 2,Transcription Factors,Tyrosine}
}
@article{morinTreatingLymphomaNow2021,
title = {Treating Lymphoma Is Now a Bit {{EZ-er}}},
author = {Morin, Ryan D. and Arthur, Sarah E. and Assouline, Sarit},
date = {2021-04-27},
journaltitle = {Blood Advances},
shortjournal = {Blood Adv},
volume = {5},
number = {8},
eprint = {33904892},
eprinttype = {pmid},
pages = {2256--2263},
issn = {2473-9537},
doi = {10.1182/bloodadvances.2020002773},
abstract = {Tazemetostat represents the first epigenetic therapy approved for the treatment of follicular lymphoma (FL). It inhibits the activity of the enhancer of zeste homolog 2 (EZH2) histone methyltransferase, the first of a multitude of epigenetic regulators that have been identified as recurrently mutated in FL and germinal center diffuse large B-cell lymphoma. In this review, we discuss the initial discovery and ongoing exploration of the functional role of EZH2 mutations in lymphomagenesis. We also explore the path from the preclinical development of tazemetostat to its approval for the treatment of relapsed FL, and potential future therapeutic applications. We discuss the clinical data that led to the approval of tazemetostat and ongoing research into the function of EZH2 and of tazemetostat in lymphomas that derive from the germinal center, which could increase the applicability of this drug in the future.},
langid = {english},
pmcid = {PMC8095133},
keywords = {Germinal Center,Humans,Lymphoma Follicular,Lymphoma Large B-Cell Diffuse,Mutation}
}
@article{moritaEfficacyAprepitantCHOP2017,
title = {Efficacy of Aprepitant for {{CHOP}} Chemotherapy-Induced Nausea, Vomiting, and Anorexia},
author = {Morita, Mihoko and Kishi, Shinji and Ookura, Miyuki and Matsuda, Yasufumi and Tai, Katsunori and Yamauchi, Takahiro and Ueda, Takanori},
date = {2017-11-01},
journaltitle = {Current Problems in Cancer},
shortjournal = {Current Problems in Cancer},
volume = {41},
number = {6},
pages = {419--425},
issn = {0147-0272},
doi = {10.1016/j.currproblcancer.2017.09.001},
url = {https://www.sciencedirect.com/science/article/pii/S014702721730140X},
urldate = {2024-01-31},
abstract = {The objective of this study was to evaluate whether aprepitant in addition to 5-HT3 receptor antagonist is useful for preventing chemotherapy-induced nausea and vomiting (CINV) and anorexia in patients receiving CHOP therapy, and to evaluate the relationship between in vivo kinetics of plasma substance P and these adverse events. Patients with malignant lymphoma who received CHOP chemotherapy or THP (THP-ADR)-COP therapy were investigated for CINV and anorexia for 5 days after the start of chemotherapy. With the first course of chemotherapy, all patients received only granisetron on day1 as an antiemetic. Patients who experienced nausea, vomiting, or anorexia exceeding grade 1 in the first course received aprepitant for 3 days in addition to granisetron with the second course of CHOP chemotherapy. Plasma substance P concentrations at 24 and 72 hours after chemotherapy were measured. Nineteen patients were evaluated. Nausea, vomiting, or anorexia was observed with the first course in 7 of 19 patients. During the second course with aprepitant, no patients experienced vomiting, and the toxicity grade of nausea, vomiting, or anorexia was decreased compared with those in the first course. Substance P concentrations showed no differences after chemotherapy, in patients with nausea, vomiting, or anorexia and in patients without. The addition of aprepitant to 5-HT3 receptor antagonist appears effective for CINV or anorexia for patients who received CHOP chemotherapy.},
keywords = {Aprepitant,CHOP chemotherapy,CINV,Malignant lymphoma,Substance P}
}
@article{moritaEfficacyAprepitantCHOP2017a,
title = {Efficacy of Aprepitant for {{CHOP}} Chemotherapy-Induced Nausea, Vomiting, and Anorexia},
author = {Morita, Mihoko and Kishi, Shinji and Ookura, Miyuki and Matsuda, Yasufumi and Tai, Katsunori and Yamauchi, Takahiro and Ueda, Takanori},
date = {2017},
journaltitle = {Current Problems in Cancer},
shortjournal = {Curr Probl Cancer},
volume = {41},
number = {6},
eprint = {29061362},
eprinttype = {pmid},
pages = {419--425},
issn = {1535-6345},
doi = {10.1016/j.currproblcancer.2017.09.001},
abstract = {The objective of this study was to evaluate whether aprepitant in addition to 5-HT3 receptor antagonist is useful for preventing chemotherapy-induced nausea and vomiting (CINV) and anorexia in patients receiving CHOP therapy, and to evaluate the relationship between in vivo kinetics of plasma substance P and these adverse events. Patients with malignant lymphoma who received CHOP chemotherapy or THP (THP-ADR)-COP therapy were investigated for CINV and anorexia for 5 days after the start of chemotherapy. With the first course of chemotherapy, all patients received only granisetron on day1 as an antiemetic. Patients who experienced nausea, vomiting, or anorexia exceeding grade 1 in the first course received aprepitant for 3 days in addition to granisetron with the second course of CHOP chemotherapy. Plasma substance P concentrations at 24 and 72 hours after chemotherapy were measured. Nineteen patients were evaluated. Nausea, vomiting, or anorexia was observed with the first course in 7 of 19 patients. During the second course with aprepitant, no patients experienced vomiting, and the toxicity grade of nausea, vomiting, or anorexia was decreased compared with those in the first course. Substance P concentrations showed no differences after chemotherapy, in patients with nausea, vomiting, or anorexia and in patients without. The addition of aprepitant to 5-HT3 receptor antagonist appears effective for CINV or anorexia for patients who received CHOP chemotherapy.},
langid = {english},
keywords = {Adult,Aged,Anorexia,Antiemetics,Antineoplastic Combined Chemotherapy Protocols,Aprepitant,CHOP chemotherapy,CINV,Cyclophosphamide,Doxorubicin,Female,Granisetron,Humans,Lymphoma,Male,Malignant lymphoma,Middle Aged,Morpholines,Nausea,Neurokinin-1 Receptor Antagonists,Prednisone,Receptors Neurokinin-1,Serotonin 5-HT3 Receptor Antagonists,Substance P,Vincristine,Vomiting}
}
@article{motoyamaPositiveNegativeRegulation2005,
title = {Positive and {{Negative Regulation}} of {{Nuclear Factor- B-mediated Transcription}} by {{I B-}} , an {{Inducible Nuclear Protein}}},
author = {Motoyama, M and Yamazaki, S and Eto-Kimura, A and Takeshige, K and Muta, T},
date = {2005-02},
journaltitle = {J Biol Chem},
volume = {280},
number = {9},
pages = {7444--7451}
}
@article{mottokGenomicAlterationsCIITA2015,
title = {Genomic {{Alterations}} in {{CIITA Are Frequent}} in {{Primary Mediastinal Large B Cell Lymphoma}} and {{Are Associated}} with {{Diminished MHC Class II Expression}}},
author = {Mottok, Anja and Woolcock, Bruce and Chan, Fong Chun and Tong, King Mong and Chong, Lauren and Farinha, Pedro and Telenius, Adèle and Chavez, Elizabeth and Ramchandani, Suvan and Drake, Marie and Boyle, Merrill and Ben-Neriah, Susana and Scott, David W. and Rimsza, Lisa M. and Siebert, Reiner and Gascoyne, Randy D. and Steidl, Christian},
date = {2015-11-17},
journaltitle = {Cell Reports},
shortjournal = {Cell Rep},
volume = {13},
number = {7},
eprint = {26549456},
eprinttype = {pmid},
pages = {1418--1431},
issn = {2211-1247},
doi = {10.1016/j.celrep.2015.10.008},
abstract = {Primary mediastinal large B cell lymphoma (PMBCL) is an aggressive non-Hodgkin's lymphoma, predominantly affecting young patients. We analyzed 45 primary PMBCL tumor biopsies and 3 PMBCL-derived cell lines for the presence of genetic alterations involving the major histocompatibility complex (MHC) class II transactivator CIITA and found frequent aberrations consisting of structural genomic rearrangements, missense, nonsense, and frame-shift mutations (53\% of primary tumor biopsies and all cell lines). We also detected intron 1 mutations in 47\% of the cases, and detailed sequence analysis strongly suggests AID-mediated aberrant somatic hypermutation as the mutational mechanism. Furthermore, we demonstrate that genomic lesions in CIITA result in decreased protein expression and reduction of MHC class II surface expression, creating an immune privilege phenotype in PMBCL. In summary, we establish CIITA alterations as a common mechanism of immune escape through reduction of MHC class II expression in PMBCL, with potential implications for future treatments targeting microenvironment-related biology.},
langid = {english},
keywords = {Cell Line,DNA Mutational Analysis,Gene Expression,Genetic Association Studies,Genetic Predisposition to Disease,Histocompatibility Antigens Class II,Humans,Introns,Lymphoma Large B-Cell Diffuse,Male,Mediastinal Neoplasms,Nuclear Proteins,Point Mutation,Sequence Deletion,Trans-Activators,Tumor Escape}
}
@article{mottokIntegrativeGenomicAnalysis2019,
title = {Integrative Genomic Analysis Identifies Key Pathogenic Mechanisms in Primary Mediastinal Large {{B-cell}} Lymphoma},
author = {Mottok, Anja and Hung, Stacy S. and Chavez, Elizabeth A. and Woolcock, Bruce and Telenius, Adèle and Chong, Lauren C. and Meissner, Barbara and Nakamura, Hisae and Rushton, Christopher and Viganò, Elena and Sarkozy, Clementine and Gascoyne, Randy D. and Connors, Joseph M. and Ben-Neriah, Susana and Mungall, Andrew and Marra, Marco A. and Siebert, Reiner and Scott, David W. and Savage, Kerry J. and Steidl, Christian},
date = {2019-09-05},
journaltitle = {Blood},
shortjournal = {Blood},
volume = {134},
number = {10},
eprint = {31292115},
eprinttype = {pmid},
pages = {802--813},
issn = {1528-0020},
doi = {10.1182/blood.2019001126},
abstract = {Primary mediastinal large B-cell lymphoma (PMBL) represents a clinically and pathologically distinct subtype of large B-cell lymphomas. Furthermore, molecular studies, including global gene expression profiling, have provided evidence that PMBL is more closely related to classical Hodgkin lymphoma (cHL). Although targeted sequencing studies have revealed a number of mutations involved in PMBL pathogenesis, a comprehensive description of disease-associated genetic alterations and perturbed pathways is still lacking. Here, we performed whole-exome sequencing of 95 PMBL tumors to inform on oncogenic driver genes and recurrent copy number alterations. The integration of somatic gene mutations with gene expression signatures provides further insights into genotype-phenotype interrelation in PMBL. We identified highly recurrent oncogenic mutations in the Janus kinase-signal transducer and activator of transcription and nuclear factor κB pathways, and provide additional evidence of the importance of immune evasion in PMBL (CIITA, CD58, B2M, CD274, and PDCD1LG2). Our analyses highlight the interferon response factor (IRF) pathway as a putative novel hallmark with frequent alterations in multiple pathway members (IRF2BP2, IRF4, and IRF8). In addition, our integrative analysis illustrates the importance of JAK1, RELB, and EP300 mutations driving oncogenic signaling. The identified driver genes were significantly more frequently mutated in PMBL compared with diffuse large B-cell lymphoma, whereas only a limited number of genes were significantly different between PMBL and cHL, emphasizing the close relation between these entities. Our study, performed on a large cohort of PMBL, highlights the importance of distinctive genetic alterations for disease taxonomy with relevance for diagnostic evaluation and therapeutic decision-making.},
langid = {english},
keywords = {Adolescent,Adult,Aged,Cohort Studies,DNA Mutational Analysis,Female,Gene Expression Profiling,Gene Expression Regulation Neoplastic,Genomics,Humans,Lymphoma Large B-Cell Diffuse,Male,Mediastinal Neoplasms,Middle Aged,Mutation,Systems Integration,Young Adult}
}
@article{mottokMolecularClassificationPrimary2018,
title = {Molecular Classification of Primary Mediastinal Large {{B-cell}} Lymphoma Using Routinely Available Tissue Specimens},
author = {Mottok, Anja and Wright, George and Rosenwald, Andreas and Ott, German and Ramsower, Colleen and Campo, Elias and Braziel, Rita M. and Delabie, Jan and Weisenburger, Dennis D. and Song, Joo Y. and Chan, Wing C. and Cook, James R. and Fu, Kai and Greiner, Tim and Smeland, Erlend and Holte, Harald and Savage, Kerry J. and Glinsmann-Gibson, Betty J. and Gascoyne, Randy D. and Staudt, Louis M. and Jaffe, Elaine S. and Connors, Joseph M. and Scott, David W. and Steidl, Christian and Rimsza, Lisa M.},
date = {2018-11-29},
journaltitle = {Blood},
shortjournal = {Blood},
volume = {132},
number = {22},
eprint = {30257882},
eprinttype = {pmid},
pages = {2401--2405},
issn = {0006-4971},
doi = {10.1182/blood-2018-05-851154},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6265647/},
urldate = {2020-03-09},
abstract = {Publisher's Note: There is a Blood Commentary on this article in this issue., A 58-gene expression-based assay aids in the molecular distinction of PMBCL and DLBCL using archival tissue biopsy specimens. , Primary mediastinal large B-cell lymphoma (PMBCL) is recognized as a distinct entity in the World Health Organization classification. Currently, the diagnosis relies on consensus of histopathology, clinical variables, and presentation, giving rise to diagnostic inaccuracy in routine practice. Previous studies have demonstrated that PMBCL can be distinguished from subtypes of diffuse large B-cell lymphoma (DLBCL) based on gene expression signatures. However, requirement of fresh-frozen biopsy material has precluded the transfer of gene expression–based assays to the clinic. Here, we developed a robust and accurate molecular classification assay (Lymph3Cx) for the distinction of PMBCL from DLBCL subtypes based on gene expression measurements in formalin-fixed, paraffin-embedded tissue. A probabilistic model accounting for classification error, comprising 58 gene features, was trained on 68 cases of PMBCL and DLBCL. Performance of the model was subsequently evaluated in an independent validation cohort of 158 cases and showed high agreement of the Lymph3Cx molecular classification with the clinicopathological diagnosis of an expert panel (frank misclassification rate, 3.8\%). Furthermore, we demonstrate reproducibility of the assay with 100\% concordance of subtype assignments at 2 independent laboratories. Future studies will determine Lymph3Cx’s utility for routine diagnostic purposes and therapeutic decision making.,},
pmcid = {PMC6265647}
}
@article{moumenHnRNPHDM2Target2005,
title = {{{hnRNP K}}: {{An HDM2 Target}} and {{Transcriptional Coactivator}} of P53 in {{Response}} to {{DNA Damage}}},
shorttitle = {{{hnRNP K}}},
author = {Moumen, Abdeladim and Masterson, Philip and O'Connor, Mark J. and Jackson, Stephen P.},
date = {2005-12-16},
journaltitle = {Cell},
shortjournal = {Cell},
volume = {123},
number = {6},
eprint = {16360036},
eprinttype = {pmid},
pages = {1065--1078},
publisher = {Elsevier},
issn = {0092-8674, 1097-4172},
doi = {10.1016/j.cell.2005.09.032},
url = {https://www.cell.com/cell/abstract/S0092-8674(05)01038-X},
urldate = {2022-09-25},
langid = {english}
}
@online{MRNACappingBiological,
title = {{{mRNA}} Capping: Biological Functions and Applications | {{Nucleic Acids Research}} | {{Oxford Academic}}},
url = {https://academic.oup.com/nar/article/44/16/7511/2460195},
urldate = {2023-01-09}
}
@online{MRNACappingBiologicala,
title = {{{mRNA}} Capping: Biological Functions and Applications | {{Nucleic Acids Research}} | {{Oxford Academic}}},
url = {https://academic.oup.com/nar/article/44/16/7511/2460195},
urldate = {2022-10-06}
}
@article{muellerGenomicPathologySLEAssociated2013,
title = {Genomic {{Pathology}} of {{SLE-Associated Copy-Number Variation}} at the {{FCGR2C}}/{{FCGR3B}}/{{FCGR2B Locus}}},
author = {Mueller, Michael and Barros, Paula and Witherden, Abigail S and Roberts, Amy L and Zhang, Zhou and Schaschl, Helmut and Yu, Chack-Yung and Hurles, Matthew E and Schaffner, Catherine and Floto, R Andres and Game, Laurence and Steinberg, Karyn Meltz and Wilson, Richard K and Graves, Tina A and Eichler, Evan E and Cook, H Terence and Vyse, Timothy J and Aitman, Timothy J},
date = {2013},
journaltitle = {Am J Hum Genet},
volume = {92},
number = {1},
pages = {28--40}
}
@article{mularoniOncodriveFMLGeneralFramework2016,
title = {{{OncodriveFML}}: A General Framework to Identify Coding and Non-Coding Regions with Cancer Driver Mutations},
shorttitle = {{{OncodriveFML}}},
author = {Mularoni, Loris and Sabarinathan, Radhakrishnan and Deu-Pons, Jordi and Gonzalez-Perez, Abel and López-Bigas, Núria},
date = {2016-06-16},
journaltitle = {Genome Biology},
shortjournal = {Genome Biol},
volume = {17},
number = {1},
eprint = {27311963},
eprinttype = {pmid},
pages = {128},
issn = {1474-760X},
doi = {10.1186/s13059-016-0994-0},
abstract = {Distinguishing the driver mutations from somatic mutations in a tumor genome is one of the major challenges of cancer research. This challenge is more acute and far from solved for non-coding mutations. Here we present OncodriveFML, a method designed to analyze the pattern of somatic mutations across tumors in both coding and non-coding genomic regions to identify signals of positive selection, and therefore, their involvement in tumorigenesis. We describe the method and illustrate its usefulness to identify protein-coding genes, promoters, untranslated regions, intronic splice regions, and lncRNAs-containing driver mutations in several malignancies.},
langid = {english},
pmcid = {PMC4910259},
keywords = {Cancer drivers,Carcinogenesis,Computational Biology,Genome Human,Humans,Local functional mutations bias,Mutation,Neoplasms,Non-coding drivers,Non-coding regions,Open Reading Frames,Promoter Regions Genetic,RNA Long Noncoding,Software}
}
@article{muppidiLossSignalingGa132014,
title = {Loss of Signaling via {{Gα13}} in Germinal Center {{B}} Cell-Derived Lymphoma},
author = {Muppidi, J. and Schmitz, R. and Green, Jesse A. and Green, Jesse A. and Xiao, Wenming and Larsen, Adrien B. and Braun, S. and An, Jinping and Xu, Ying and Rosenwald, A. and Ott, G. and Gascoyne, R. and Rimsza, L. and Campo, E. and Jaffe, E. and Delabie, J. and Smeland, E. and Braziel, R. and Tubbs, R. and Cook, J. and Weisenburger, D. and Chan, W. and Vaidehi, N. and Staudt, L. and Cyster, J.},
date = {2014},
journaltitle = {Nature},
shortjournal = {Nature},
volume = {516},
pages = {254--258},
doi = {10.1038/nature13765}
}
@article{nadeuGenomicEpigenomicInsights2020,
title = {Genomic and Epigenomic Insights into the Origin, Pathogenesis and Clinical Behavior of Mantle Cell Lymphoma Subtypes.},
author = {Nadeu, F. and Martín-García, D. and Clot, G. and Díaz-Navarro, A. and Duran-Ferrer, M. and Navarro, A. and Vilarrasa-Blasi, Roser and Kulis, M. and Royo, R. and Gutiérrez-Abril, J. and Valdés-Mas, R. and López, C. and Chapaprieta, V. and Puiggrós, Montserrat and Castellano, G. and Costa, D. and Aymerich, M. and Jares, P. and Espinet, B. and Muntañola, A. and Ribera‐Cortada, Inmaculada and Siebert, R. and Colomer, D. and Torrents, D. and Giné, E. and López-Guillermo, A. and Küppers, R. and Martín-Subero, J. and Puente, X. and Beà, S. and Campo, E.},
date = {2020},
journaltitle = {Blood},
shortjournal = {Blood},
doi = {10.1182/blood.2020005289}
}
@article{nadeuIgCallerReconstructingImmunoglobulin2020,
title = {{{IgCaller}} for Reconstructing Immunoglobulin Gene Rearrangements and Oncogenic Translocations from Whole-Genome Sequencing in Lymphoid Neoplasms},
author = {Nadeu, Ferran and Mas-de-Les-Valls, Rut and Navarro, Alba and Royo, Romina and Martín, Silvia and Villamor, Neus and Suárez-Cisneros, Helena and Mares, Rosó and Lu, Junyan and Enjuanes, Anna and Rivas-Delgado, Alfredo and Aymerich, Marta and Baumann, Tycho and Colomer, Dolors and Delgado, Julio and Morin, Ryan D. and Zenz, Thorsten and Puente, Xose S. and Campbell, Peter J. and Beà, Sílvia and Maura, Francesco and Campo, Elías},
date = {2020-07-07},
journaltitle = {Nature Communications},
shortjournal = {Nat Commun},
volume = {11},
number = {1},
eprint = {32636395},
eprinttype = {pmid},
pages = {3390},
issn = {2041-1723},
doi = {10.1038/s41467-020-17095-7},
abstract = {Immunoglobulin (Ig) gene rearrangements and oncogenic translocations are routinely assessed during the characterization of B cell neoplasms and stratification of patients with distinct clinical and biological features, with the assessment done using Sanger sequencing, targeted next-generation sequencing, or fluorescence in situ hybridization (FISH). Currently, a complete Ig characterization cannot be extracted from whole-genome sequencing (WGS) data due to the inherent complexity of the Ig loci. Here, we introduce IgCaller, an algorithm designed to fully characterize Ig gene rearrangements and oncogenic translocations from short-read WGS data. Using a cohort of 404 patients comprising different subtypes of B cell neoplasms, we demonstrate that IgCaller identifies both heavy and light chain rearrangements to provide additional information on their functionality, somatic mutational status, class switch recombination, and oncogenic Ig translocations. Our data thus support IgCaller to be a reliable alternative to Sanger sequencing and FISH for studying the genetic properties of the Ig loci.},
langid = {english},
pmcid = {PMC7341758},
keywords = {Algorithms,Cohort Studies,Genes Immunoglobulin,Genome Human,Hematologic Neoplasms,High-Throughput Nucleotide Sequencing,Humans,Immunoglobulin Class Switching,In Situ Hybridization Fluorescence,Lymphoma B-Cell,Oncogenes,Software,Translocation Genetic,Whole Genome Sequencing}
}
@article{nagarajDeepProteomeTranscriptome2011,
title = {Deep Proteome and Transcriptome Mapping of a Human Cancer Cell Line},
author = {Nagaraj, Nagarjuna and Wisniewski, Jacek R. and Geiger, Tamar and Cox, Juergen and Kircher, Martin and Kelso, Janet and Pääbo, Svante and Mann, Matthias},
date = {2011-01-01},
journaltitle = {Molecular Systems Biology},
volume = {7},
number = {1},
eprint = {22068331},
eprinttype = {pmid},
pages = {548},
issn = {1744-4292, 1744-4292},
doi = {10.1038/msb.2011.81},
url = {http://msb.embopress.org/content/7/1/548},
urldate = {2018-08-30},
abstract = {While the number and identity of proteins expressed in a single human cell type is currently unknown, this fundamental question can be addressed by advanced mass spectrometry (MS)‐based proteomics. Online liquid chromatography coupled to high‐resolution MS and MS/MS yielded 166 420 peptides with unique amino‐acid sequence from HeLa cells. These peptides identified 10 255 different human proteins encoded by 9207 human genes, providing a lower limit on the proteome in this cancer cell line. Deep transcriptome sequencing revealed transcripts for nearly all detected proteins. We calculate copy numbers for the expressed proteins and show that the abundances of {$>$}90\% of them are within a factor 60 of the median protein expression level. Comparisons of the proteome and the transcriptome, and analysis of protein complex databases and GO categories, suggest that we achieved deep coverage of the functional transcriptome and the proteome of a single cell type.},
langid = {english},
keywords = {mass spectrometry,proteomics,RNA‐Seq,systems biology,transcriptomics}
}
@article{nagelkerkeImmunomodulationIVIgRole2014,
title = {Immunomodulation by {{IVIg}} and the {{Role}} of {{Fc-Gamma Receptors}}: {{Classic Mechanisms}} of {{Action}} after All?},
author = {Nagelkerke, Sietse Q and Kuijpers, Taco W},
date = {2014},
journaltitle = {Frontiers in Immunology},
volume = {5},
number = {8232},
pages = {674}
}
@article{nagelkerkeNonallelicHomologousRecombination2015,
title = {Nonallelic Homologous Recombination of the {{FCGR2}}/3 Locus Results in Copy Number Variation and Novel Chimeric {{FCGR2}} Genes with Aberrant Functional Expression},
author = {Nagelkerke, S Q and Tacke, C E and Breunis, W B and Geissler, J and Sins, J and Appelhof, B and Berg, T and family=Boer, given=M, prefix=de, useprefix=false and Kuijpers, T W},
date = {2015},
journaltitle = {Genes and Immunity},
volume = {16},
number = {6},
eprint = {26133275},
eprinttype = {pmid},
pages = {422--429},
issn = {1466-4879},
doi = {10.1038/gene.2015.25},
url = {http://dx.doi.org/10.1038/gene.2015.25},
abstract = {The human FCGR2/3 locus, containing five highly homologous genes encoding the major IgG receptors, shows extensive copy number variation (CNV) associated with susceptibility to autoimmune diseases. Having genotyped {$>$}4000 individuals, we show that all CNV at this locus can be explained by nonallelic homologous recombination (NAHR) of the two paralogous repeats that constitute the majority of the locus, and describe four distinct CNV regions (CNRs) with a highly variable prevalence in the population. Apart from CNV, NAHR events also created several hitherto unidentified chimeric FCGR2 genes. These include an FCGR2A/2C chimeric gene that causes a decreased expression of FcγRIIa on phagocytes, resulting in a decreased production of reactive oxygen species in response to immune complexes, compared with wild-type FCGR2A. Conversely, FCGR2C/2A chimeric genes were identified to lead to an increased expression of FCGR2C. Finally, a rare FCGR2B null-variant allele was found, in which a polymorphic stop codon of FCGR2C is introduced into one FCGR2B gene, resulting in a 50\% reduction in protein expression. Our study on CNRs and the chimeric genes is essential for the correct interpretation of association studies on FCGR genes as a determinant for disease susceptibility, and may explain some as yet unidentified extreme phenotypes of immune-mediated disease.}
}
@article{nakamuraTranslocationsInvolvingImmunoglobulin2008,
title = {Translocations Involving the Immunoglobulin Heavy Chain Gene Locus Predict Better Survival in Gastric Diffuse Large {{B-cell}} Lymphoma},
author = {Nakamura, S and Ye, H and Bacon, C and Goatly, A and Liu, H and Kerr, L and Banham, A and Streubel, B and Yao, T and Tsuneyoshi, M and Savio, A and Takeshita, M and Dartigues, P and Ruskone-Fourmestraux, A and Matsumoto, T and Iida, M and Du, M},
date = {2008},
journaltitle = {Clin Cancer Res},
volume = {14},
number = {10},
pages = {3002--3010}
}
@article{natarajanHnRNPKLysineSpecific2022,
title = {{{HnRNPK}} and Lysine Specific Histone Demethylase-1 Regulates {{IP-10 mRNA}} Stability in Monocytes},
author = {Natarajan, Kartiga and Sundaramoorthy, Arun and Shanmugam, Narkunaraja},
date = {2022-04-05},
journaltitle = {European Journal of Pharmacology},
shortjournal = {European Journal of Pharmacology},
volume = {920},
pages = {174683},
issn = {0014-2999},
doi = {10.1016/j.ejphar.2021.174683},
url = {https://www.sciencedirect.com/science/article/pii/S0014299921008396},
urldate = {2022-09-22},
abstract = {Altered mRNA metabolism is a feature of many inflammatory diseases. Post transcriptional regulation of interferon-γ-inducible protein (IP)-10 has been uncharacterized in diabetes conditions. RNA-affinity capture method and RNA immuno-precipitation revealed S100b treatment increased the binding of heterogeneous nuclear ribonucleoprotein (hnRNP)K to the IP-10 3′UTR and increased IP-10 mRNA accumulation. Luciferase activity assay using reporter plasmids showed involvement of IP-10 3′UTR. Knocking down of hnRNPK destabilized S100b induced IP-10 mRNA accumulation. S100b promoted the translocation of hnRNPK from nucleus to the cytoplasm and this was confirmed by phosphomimetic S284/353D mutant and non-phosphatable S284/353A hnRNPK mutant. S100b treatment demethylates hnRNPK at Lys219 by Lysine Specific Demethylase (LSD)-1. HnRNPKK219I, a demethylation defective mutant increased IP-10 mRNA stability. Apparently, triple mutant hnRNPKK219I/S284D/353D promoted IP-10 mRNA stability. Interestingly, knocking down LSD-1 abolished S100b induced IP-10 mRNA accumulation. These observations show for the first time that IP-10 mRNA stability is dynamically regulated by Lysine demethylation of hnRNPK by LSD-1. These results indicate that hnRNPK plays an important role in IP-10 mRNA stability induced by S100b which could exacerbate monocyte activation, relevant to the pathogenesis of diabetic complications like atherosclerosis.},
langid = {english},
keywords = {hnRNPK,IP-10,LSD-1,mRNA stability,Non-histone demethylation,RAGE}
}
@article{nazarovKHDomainPolyBinding2019,
title = {{{KH-Domain Poly}}({{C}})-{{Binding Proteins}} as {{Versatile Regulators}} of {{Multiple Biological Processes}}},
author = {Nazarov, I. B. and Bakhmet, E. I. and Tomilin, A. N.},
date = {2019-03},
journaltitle = {Biochemistry. Biokhimiia},
shortjournal = {Biochemistry (Mosc)},
volume = {84},
number = {3},
eprint = {31221059},
eprinttype = {pmid},
pages = {205--219},
issn = {1608-3040},
doi = {10.1134/S0006297919030039},
abstract = {Five known members of the family of KH-domain poly(C)-binding proteins (Pcbp1-4, hnRNP-K) have an unusually broad spectrum of cellular functions that include regulation of gene transcription, regulation of pre-mRNA processing, splicing, mRNA stability, translational silencing and enhancement, the control of iron turnover, and many others. Mechanistically, these proteins act via nucleic acid binding and protein-protein interactions. Through performing these multiple tasks, the KH-domain poly(C)-binding family members are involved in a wide variety of biological processes such as embryonic development, cell differentiation, and cancer. Deregulation of KH-domain protein expression is frequently associated with severe developmental defects and neoplasia. This review summarizes progress in studies of the KH-domain proteins made over past two decades. The review also reports our recent finding implying an involvement of the KH-factor Pcbp1 into control of transition from naïve to primed pluripotency cell state.},
langid = {english},
keywords = {Animals,Heterogeneous-Nuclear Ribonucleoprotein K,Humans,Pluripotent Stem Cells}
}
@article{nazimCompetitiveRegulationAlternative2017,
title = {Competitive Regulation of Alternative Splicing and Alternative Polyadenylation by {{hnRNP H}} and {{CstF64}} Determines Acetylcholinesterase Isoforms},
author = {Nazim, Mohammad and Masuda, Akio and Rahman, Mohammad Alinoor and Nasrin, Farhana and Takeda, Jun-ichi and Ohe, Kenji and Ohkawara, Bisei and Ito, Mikako and Ohno, Kinji},
date = {2017-02-17},
journaltitle = {Nucleic Acids Research},
shortjournal = {Nucleic Acids Research},
volume = {45},
number = {3},
pages = {1455--1468},
issn = {0305-1048},
doi = {10.1093/nar/gkw823},
url = {https://doi.org/10.1093/nar/gkw823},
urldate = {2022-09-27},
abstract = {Acetylcholinesterase (AChE), encoded by the ACHE gene, hydrolyzes the neurotransmitter acetylcholine to terminate synaptic transmission. Alternative splicing close to the 3΄ end generates three distinct isoforms of AChET, AChEH and AChER. We found that hnRNP H binds to two specific G-runs in exon 5a of human ACHE and activates the distal alternative 3΄ splice site (ss) between exons 5a and 5b to generate AChET. Specific effect of hnRNP H was corroborated by siRNA-mediated knockdown and artificial tethering of hnRNP H. Furthermore, hnRNP H competes for binding of CstF64 to the overlapping binding sites in exon 5a, and suppresses the selection of a cryptic polyadenylation site (PAS), which additionally ensures transcription of the distal 3΄ ss required for the generation of AChET. Expression levels of hnRNP H were positively correlated with the proportions of the AChET isoform in three different cell lines. HnRNP H thus critically generates AChET by enhancing the distal 3΄ ss and by suppressing the cryptic PAS. Global analysis of CLIP-seq and RNA-seq also revealed that hnRNP H competitively regulates alternative 3΄ ss and alternative PAS in other genes. We propose that hnRNP H is an essential factor that competitively regulates alternative splicing and alternative polyadenylation.}
}
@article{necklesHNRNPH1dependentSplicingFusion2019,
title = {{{HNRNPH1-dependent}} Splicing of a Fusion Oncogene Reveals a Targetable {{RNA G-quadruplex}} Interaction},
author = {Neckles, Carla and Boer, Robert E. and Aboreden, Nicholas and Cross, Allison M. and Walker, Robert L. and Kim, Bong-Hyun and Kim, Suntae and John S. Schneekloth, Jr and Caplen, Natasha J.},
date = {2019-12},
journaltitle = {RNA},
volume = {25},
number = {12},
eprint = {31511320},
eprinttype = {pmid},
pages = {1731},
publisher = {Cold Spring Harbor Laboratory Press},
doi = {10.1261/rna.072454.119},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6859848/},
urldate = {2022-10-15},
abstract = {The primary oncogenic event in ∼85\% of Ewing sarcomas is a chromosomal translocation that generates a fusion oncogene encoding an aberrant transcription factor. The exact genomic breakpoints within the translocated genes, EWSR1 and FLI1, vary; ...},
langid = {english}
}
@article{newmanIntegratedDigitalError2016,
title = {Integrated Digital Error Suppression for Improved Detection of Circulating Tumor {{DNA}}},
author = {Newman, Aaron M and Lovejoy, Alexander F and Klass, Daniel M and Kurtz, David M and Chabon, Jacob J and Scherer, Florian and Stehr, Henning and Liu, Chih Long and Bratman, Scott V and Say, Carmen and Zhou, Li and Carter, Justin N and West, Robert B and Sledge Jr, George W and Shrager, Joseph B and Loo, Billy W and Neal, Joel W and Wakelee, Heather A and Diehn, Maximilian and Alizadeh, Ash A},
date = {2016-03},
journaltitle = {Nat Biotechnol},
pages = {1--14}
}
@article{newmanUltrasensitiveMethodQuantitating,
title = {An Ultrasensitive Method for Quantitating Circulating Tumor {{DNA}} with Broad Patient Coverage.},
author = {Newman, Aaron M and Bratman, Scott V and To, Jacqueline and Wynne, Jacob F and Eclov, Neville C W and Modlin, Leslie A and Liu, Chih Long and Neal, Joel W and Wakelee, Heather A and Merritt, Robert E and Shrager, Joseph B and Loo, Billy W and Alizadeh, Ash A and Diehn, Maximilian},
journaltitle = {Nature Medicine}
}
@article{ngoOncogenicallyActiveMYD882011,
title = {Oncogenically Active {{MYD88}} Mutations in Human Lymphoma},
author = {Ngo, Vu N. and Young, Ryan M. and Schmitz, Roland and Jhavar, Sameer and Xiao, Wenming and Lim, Kian-Huat and Kohlhammer, Holger and Xu, Weihong and Yang, Yandan and Zhao, Hong and Shaffer, Arthur L. and Romesser, Paul and Wright, George and Powell, John and Rosenwald, Andreas and Muller-Hermelink, Hans Konrad and Ott, German and Gascoyne, Randy D. and Connors, Joseph M. and Rimsza, Lisa M. and Campo, Elias and Jaffe, Elaine S. and Delabie, Jan and Smeland, Erlend B. and Fisher, Richard I. and Braziel, Rita M. and Tubbs, Raymond R. and Cook, J. R. and Weisenburger, Denny D. and Chan, Wing C. and Staudt, Louis M.},
date = {2011-02-03},
journaltitle = {Nature},
shortjournal = {Nature},
volume = {470},
number = {7332},
eprint = {21179087},
eprinttype = {pmid},
pages = {115--119},
issn = {1476-4687},
doi = {10.1038/nature09671},
abstract = {The activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) remains the least curable form of this malignancy despite recent advances in therapy. Constitutive nuclear factor (NF)-κB and JAK kinase signalling promotes malignant cell survival in these lymphomas, but the genetic basis for this signalling is incompletely understood. Here we describe the dependence of ABC DLBCLs on MYD88, an adaptor protein that mediates toll and interleukin (IL)-1 receptor signalling, and the discovery of highly recurrent oncogenic mutations affecting MYD88 in ABC DLBCL tumours. RNA interference screening revealed that MYD88 and the associated kinases IRAK1 and IRAK4 are essential for ABC DLBCL survival. High-throughput RNA resequencing uncovered MYD88 mutations in ABC DLBCL lines. Notably, 29\% of ABC DLBCL tumours harboured the same amino acid substitution, L265P, in the MYD88 Toll/IL-1 receptor (TIR) domain at an evolutionarily invariant residue in its hydrophobic core. This mutation was rare or absent in other DLBCL subtypes and Burkitt's lymphoma, but was observed in 9\% of mucosa-associated lymphoid tissue lymphomas. At a lower frequency, additional mutations were observed in the MYD88 TIR domain, occurring in both the ABC and germinal centre B-cell-like (GCB) DLBCL subtypes. Survival of ABC DLBCL cells bearing the L265P mutation was sustained by the mutant but not the wild-type MYD88 isoform, demonstrating that L265P is a gain-of-function driver mutation. The L265P mutant promoted cell survival by spontaneously assembling a protein complex containing IRAK1 and IRAK4, leading to IRAK4 kinase activity, IRAK1 phosphorylation, NF-κB signalling, JAK kinase activation of STAT3, and secretion of IL-6, IL-10 and interferon-β. Hence, the MYD88 signalling pathway is integral to the pathogenesis of ABC DLBCL, supporting the development of inhibitors of IRAK4 kinase and other components of this pathway for the treatment of tumours bearing oncogenic MYD88 mutations.},
langid = {english},
pmcid = {PMC5024568},
keywords = {Amino Acid Sequence,Amino Acid Substitution,Burkitt Lymphoma,Cell Line Tumor,Cell Survival,Cytokines,High-Throughput Nucleotide Sequencing,Humans,Hydrophobic and Hydrophilic Interactions,Interleukin-1 Receptor-Associated Kinases,Janus Kinases,Lymphoma B-Cell Marginal Zone,Lymphoma Large B-Cell Diffuse,Molecular Sequence Data,Mutant Proteins,Mutation,Myeloid Differentiation Factor 88,NF-kappa B,Oncogenes,Phosphorylation,Protein Structure Tertiary,Receptors Interleukin-1,RNA Interference,Sequence Analysis RNA,Signal Transduction,STAT3 Transcription Factor,Toll-Like Receptors}
}
@article{nicholsLossHeterozygosityEssential2020,
title = {Loss of Heterozygosity of Essential Genes Represents a Widespread Class of Potential Cancer Vulnerabilities},
author = {Nichols, Caitlin A. and Gibson, William J. and Brown, Meredith S. and Kosmicki, Jack A. and Busanovich, John P. and Wei, Hope and Urbanski, Laura M. and Curimjee, Naomi and Berger, Ashton C. and Gao, Galen F. and Cherniack, Andrew D. and Dhe-Paganon, Sirano and Paolella, Brenton R. and Beroukhim, Rameen},
date = {2020-05-20},
journaltitle = {Nature Communications},
shortjournal = {Nat Commun},
volume = {11},
number = {1},
pages = {2517},
publisher = {Nature Publishing Group},
issn = {2041-1723},
doi = {10.1038/s41467-020-16399-y},
url = {https://www.nature.com/articles/s41467-020-16399-y},
urldate = {2023-01-10},
abstract = {Alterations in non-driver genes represent an emerging class of potential therapeutic targets in cancer. Hundreds to thousands of non-driver genes undergo loss of heterozygosity (LOH) events per tumor, generating discrete differences between tumor and normal cells. Here we interrogate LOH of polymorphisms in essential genes as a novel class of therapeutic targets. We hypothesized that monoallelic inactivation of the allele retained in tumors can selectively kill cancer cells but not somatic cells, which retain both alleles. We identified 5664 variants in 1278 essential genes that undergo LOH in cancer and evaluated the potential for each to be targeted using allele-specific gene-editing, RNAi, or small-molecule approaches. We further show that allele-specific inactivation of either of two essential genes (PRIM1 and EXOSC8) reduces growth of cells harboring that allele, while cells harboring the non-targeted allele remain intact. We conclude that LOH of essential genes represents a rich class of non-driver cancer vulnerabilities.},
issue = {1},
langid = {english},
keywords = {Cancer,Cancer genomics,Molecular biology}
}
@article{nieIntegrativeAnalysisTranscriptomic2007,
title = {Integrative {{Analysis}} of {{Transcriptomic}} and {{Proteomic Data}}: {{Challenges}}, {{Solutions}} and {{Applications}}},
shorttitle = {Integrative {{Analysis}} of {{Transcriptomic}} and {{Proteomic Data}}},
author = {Nie, Lei and Wu, Gang and Culley, David E. and Scholten, Johannes C. M. and Zhang, Weiwen},
date = {2007-01-01},
journaltitle = {Critical Reviews in Biotechnology},
volume = {27},
number = {2},
eprint = {17578703},
eprinttype = {pmid},
pages = {63--75},
issn = {0738-8551},
doi = {10.1080/07388550701334212},
url = {https://doi.org/10.1080/07388550701334212},
urldate = {2018-08-30},
abstract = {Recent advances in high-throughput technologies enable quantitative monitoring of the abundance of various biological molecules and allow determination of their variation between biological states on a genomic scale. Two popular platforms are DNA microarrays that measure messenger RNA transcript levels, and gel-free proteomic analyses that quantify protein abundance. Obviously, no single approach can fully unravel the complexities of fundamental biology and it is equally clear that integrative analysis of multiple levels of gene expression would be valuable in this endeavor. However, most integrative transcriptomic and proteomic studies have thus far either failed to find a correlation or only observed a weak correlation. In addition to various biological factors, it is suggested that the poor correlation could be quite possibly due to the inadequacy of available statistical tools to compensate for biases in the data collection methodologies. To address this issue, attempts have recently been made to systematically investigate the correlation patterns between transcriptomic and proteomic datasets, and to develop sophisticated statistical tools to improve the chances of capturing a relationship. The goal of these efforts is to enhance understanding of the relationship between transcriptomes and proteomes so that integrative analyses may be utilized to reveal new biological insights that are not accessible through one-dimensional datasets. In this review, we outline some of the challenges associated with integrative analyses and present some preliminary statistical solutions. In addition, some new applications of integrated transcriptomic and proteomic analysis to the investigation of post-transcriptional regulation are also discussed.},
keywords = {integration,proteomics,statistical,transcriptomics}
}
@article{nielsenMethodsSampleAcquisition2014,
title = {Methods for Sample Acquisition and Processing of Serial Blood and Tumor Biopsies for Multicenter Diffuse Large {{B-cell}} Lymphoma Clinical Trials.},
author = {Nielsen, Torsten Holm and Diaz, Zuanel and Christodoulopoulos, Rosa and Charbonneau, Fredrick and Qureshi, Samia and Rousseau, Caroline and Benlimame, Naciba and Camlioglu, Errol and Constantin, André Marc and Oros, Kathleen Klein and Krumsiek, Jan and Crump, Michael and Morin, Ryan D and Cerchietti, Leandro and Johnson, Nathalie A and Petrogiannis-Haliotis, Tina and Miller, Wilson H and Assouline, Sarit E and Mann, Koren K},
date = {2014-12},
journaltitle = {Cancer epidemiology, biomarkers \& prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology},
volume = {23},
number = {12},
pages = {2688--2693}
}
@article{nik-zainalLifeHistory212012,
title = {The Life History of 21 Breast Cancers},
author = {Nik-Zainal, Serena and Van Loo, Peter and Wedge, David C. and Alexandrov, Ludmil B. and Greenman, Christopher D. and Lau, King Wai and Raine, Keiran and Jones, David and Marshall, John and Ramakrishna, Manasa and Shlien, Adam and Cooke, Susanna L. and Hinton, Jonathan and Menzies, Andrew and Stebbings, Lucy A. and Leroy, Catherine and Jia, Mingming and Rance, Richard and Mudie, Laura J. and Gamble, Stephen J. and Stephens, Philip J. and McLaren, Stuart and Tarpey, Patrick S. and Papaemmanuil, Elli and Davies, Helen R. and Varela, Ignacio and McBride, David J. and Bignell, Graham R. and Leung, Kenric and Butler, Adam P. and Teague, Jon W. and Martin, Sancha and Jönsson, Goran and Mariani, Odette and Boyault, Sandrine and Miron, Penelope and Fatima, Aquila and Langerød, Anita and Aparicio, Samuel A. J. R. and Tutt, Andrew and Sieuwerts, Anieta M. and Borg, Åke and Thomas, Gilles and Salomon, Anne Vincent and Richardson, Andrea L. and Børresen-Dale, Anne-Lise and Futreal, P. Andrew and Stratton, Michael R. and Campbell, Peter J. and {Breast Cancer Working Group of the International Cancer Genome Consortium}},
date = {2012-05-25},
journaltitle = {Cell},
shortjournal = {Cell},
volume = {149},
number = {5},
eprint = {22608083},
eprinttype = {pmid},
pages = {994--1007},
issn = {1097-4172},
doi = {10.1016/j.cell.2012.04.023},
abstract = {Cancer evolves dynamically as clonal expansions supersede one another driven by shifting selective pressures, mutational processes, and disrupted cancer genes. These processes mark the genome, such that a cancer's life history is encrypted in the somatic mutations present. We developed algorithms to decipher this narrative and applied them to 21 breast cancers. Mutational processes evolve across a cancer's lifespan, with many emerging late but contributing extensive genetic variation. Subclonal diversification is prominent, and most mutations are found in just a fraction of tumor cells. Every tumor has a dominant subclonal lineage, representing more than 50\% of tumor cells. Minimal expansion of these subclones occurs until many hundreds to thousands of mutations have accumulated, implying the existence of long-lived, quiescent cell lineages capable of substantial proliferation upon acquisition of enabling genomic changes. Expansion of the dominant subclone to an appreciable mass may therefore represent the final rate-limiting step in a breast cancer's development, triggering diagnosis.},
langid = {english},
pmcid = {PMC3428864},
keywords = {Algorithms,Breast Neoplasms,Cell Transformation Neoplastic,Chromosome Aberrations,Clonal Evolution,Female,Humans,Mutation,Point Mutation}
}
@article{nileathlobhairEvolutionaryHistoryDogs2018,
title = {The Evolutionary History of Dogs in the {{Americas}}},
author = {Ní Leathlobhair, Máire and Perri, Angela R. and Irving-Pease, Evan K. and Witt, Kelsey E. and Linderholm, Anna and Haile, James and Lebrasseur, Ophelie and Ameen, Carly and Blick, Jeffrey and Boyko, Adam R. and Brace, Selina and Cortes, Yahaira Nunes and Crockford, Susan J. and Devault, Alison and Dimopoulos, Evangelos A. and Eldridge, Morley and Enk, Jacob and Gopalakrishnan, Shyam and Gori, Kevin and Grimes, Vaughan and Guiry, Eric and Hansen, Anders J. and Hulme-Beaman, Ardern and Johnson, John and Kitchen, Andrew and Kasparov, Aleksei K. and Kwon, Young-Mi and Nikolskiy, Pavel A. and Lope, Carlos Peraza and Manin, Aurélie and Martin, Terrance and Meyer, Michael and Myers, Kelsey Noack and Omura, Mark and Rouillard, Jean-Marie and Pavlova, Elena Y. and Sciulli, Paul and Sinding, Mikkel-Holger S. and Strakova, Andrea and Ivanova, Varvara V. and Widga, Christopher and Willerslev, Eske and Pitulko, Vladimir V. and Barnes, Ian and Gilbert, M. Thomas P. and Dobney, Keith M. and Malhi, Ripan S. and Murchison, Elizabeth P. and Larson, Greger and Frantz, Laurent A. F.},
date = {2018-07-06},
journaltitle = {Science (New York, N.Y.)},
shortjournal = {Science},
volume = {361},
number = {6397},
eprint = {29976825},
eprinttype = {pmid},
pages = {81--85},
issn = {1095-9203},
doi = {10.1126/science.aao4776},
abstract = {Dogs were present in the Americas before the arrival of European colonists, but the origin and fate of these precontact dogs are largely unknown. We sequenced 71 mitochondrial and 7 nuclear genomes from ancient North American and Siberian dogs from time frames spanning \textasciitilde 9000 years. Our analysis indicates that American dogs were not derived from North American wolves. Instead, American dogs form a monophyletic lineage that likely originated in Siberia and dispersed into the Americas alongside people. After the arrival of Europeans, native American dogs almost completely disappeared, leaving a minimal genetic legacy in modern dog populations. The closest detectable extant lineage to precontact American dogs is the canine transmissible venereal tumor, a contagious cancer clone derived from an individual dog that lived up to 8000 years ago.},
langid = {english},
keywords = {Americas,Animals,Biological Evolution,Cell Nucleus,Dog Diseases,Dogs,Domestication,Genome Mitochondrial,Human Migration,Humans,Neoplasms,Phylogeny,Sexually Transmitted Diseases,Siberia,Wolves}
}
@article{niuUSP10InhibitsGenotoxic2013,
title = {{{USP10}} Inhibits Genotoxic {{NF-κB}} Activation by {{MCPIP1-facilitated}} Deubiquitination of {{NEMO}}.},
author = {Niu, Jixiao and Shi, Yuling and Xue, Jingyan and Miao, Ruidong and Huang, Shengping and Wang, Tianyi and Wu, Jiong and Fu, Mingui and Wu, Zhao-Hui},
date = {2013-12},
journaltitle = {The EMBO Journal},
volume = {32},
number = {24},
pages = {3206--3219}
}
@article{nobleDevelopmentSignificanceMouse2019,
title = {Development and {{Significance}} of {{Mouse Models}} in {{Lymphoma Research}}},
author = {Noble, Jordan N. and Mishra, Anjali},
date = {2019-04-01},
journaltitle = {Current Hematologic Malignancy Reports},
shortjournal = {Curr Hematol Malig Rep},
volume = {14},
number = {2},
pages = {119--126},
issn = {1558-822X},
doi = {10.1007/s11899-019-00504-0},
url = {https://doi.org/10.1007/s11899-019-00504-0},
urldate = {2021-11-30},
abstract = {Animal models have played an indispensable role in interpreting cancer gene functions, pathogenesis of disease, and in the development of innovative therapeutic approaches targeting aberrant biological pathways in human cancers.},
langid = {english}
}
@article{noensieStrategyDiseaseGene2001,
title = {A Strategy for Disease Gene Identification through Nonsense-Mediated {{mRNA}} Decay Inhibition},
author = {Noensie, E. N. and Dietz, H. C.},
date = {2001-05},
journaltitle = {Nature Biotechnology},
shortjournal = {Nat. Biotechnol.},
volume = {19},
number = {5},
eprint = {11329012},
eprinttype = {pmid},
pages = {434--439},
issn = {1087-0156},
doi = {10.1038/88099},
abstract = {Premature termination codons (PTCs) have been shown to initiate degradation of mutant transcripts through the nonsense-mediated messenger RNA (mRNA) decay (NMD) pathway. We report a strategy, termed gene identification by NMD inhibition (GINI), to identify genes harboring nonsense codons that underlie human diseases. In this strategy, the NMD pathway is pharmacologically inhibited in cultured patient cells, resulting in stabilization of nonsense transcripts. To distinguish stabilized nonsense transcripts from background transcripts upregulated by drug treatment, drug-induced expression changes are measured in control and disease cell lines with complementary DNA (cDNA) microarrays. Transcripts are ranked by a nonsense enrichment index (NEI), which relates expression changes for a given transcript in NMD-inhibited control and patient cell lines. The most promising candidates can be selected using information such as map location or biological function; however, an important advantage of the GINI strategy is that a priori information is not essential for disease gene identification. GINI was tested on colon cancer and Sandhoff disease cell lines, which contained previously characterized nonsense mutations in the MutL homolog 1 (MLH1) and hexosaminidase B (HEXB) genes, respectively. A list of genes was produced in which the MLH1 and HEXB genes were among the top 1\% of candidates, thus validating the strategy.},
langid = {english},
keywords = {Adaptor Proteins Signal Transducing,Bacterial Proteins,beta-Hexosaminidase beta Chain,beta-N-Acetylhexosaminidases,Carrier Proteins,Cell Line,Codon Nonsense,Codon Terminator,Colonic Neoplasms,DNA-Binding Proteins,Hexosaminidase B,Humans,Male,MutL Protein Homolog 1,Neoplasm Proteins,Nuclear Proteins,Oligonucleotide Array Sequence Analysis,Peptide Chain Termination Translational,RNA Messenger,Sandhoff Disease,Tumor Cells Cultured,Tumor Suppressor Protein p53}
}
@article{nogaiControlsConstitutiveNF2013,
title = {I {{B-}} Controls the Constitutive {{NF- B}} Target Gene Network and Survival of {{ABC DLBCL}}},
author = {Nogai, H and Wenzel, S S and Hailfinger, S and Grau, M and Kaergel, E and Seitz, V and Wollert-Wulf, B and Pfeifer, M and Wolf, A and Frick, M and Dietze, K and Madle, H and Tzankov, A and Hummel, M and Dörken, B and Scheidereit, C and Janz, M and Lenz, P and Thome, M and Lenz, G},
date = {2013-09},
journaltitle = {Blood},
volume = {122},
number = {13},
pages = {2242--2250}
}
@article{nouriSpectralClusteringbasedMethod2018,
title = {A Spectral Clustering-Based Method for Identifying Clones from High-Throughput {{B}} Cell Repertoire Sequencing Data},
author = {Nouri, Nima and Kleinstein, Steven H.},
date = {2018-07-01},
journaltitle = {Bioinformatics (Oxford, England)},
shortjournal = {Bioinformatics},
volume = {34},
number = {13},
eprint = {29949968},
eprinttype = {pmid},
pages = {i341-i349},
issn = {1367-4811},
doi = {10.1093/bioinformatics/bty235},
abstract = {Motivation: B cells derive their antigen-specificity through the expression of Immunoglobulin (Ig) receptors on their surface. These receptors are initially generated stochastically by somatic re-arrangement of the DNA and further diversified following antigen-activation by a process of somatic hypermutation, which introduces mainly point substitutions into the receptor DNA at a high rate. Recent advances in next-generation sequencing have enabled large-scale profiling of the B cell Ig repertoire from blood and tissue samples. A key computational challenge in the analysis of these data is partitioning the sequences to identify descendants of a common B cell (i.e. a clone). Current methods group sequences using a fixed distance threshold, or a likelihood calculation that is computationally-intensive. Here, we propose a new method based on spectral clustering with an adaptive threshold to determine the local sequence neighborhood. Validation using simulated and experimental datasets demonstrates that this method has high sensitivity and specificity compared to a fixed threshold that is optimized for these measures. In addition, this method works on datasets where choosing an optimal fixed threshold is difficult and is more computationally efficient in all cases. The ability to quickly and accurately identify members of a clone from repertoire sequencing data will greatly improve downstream analyses. Clonally-related sequences cannot be treated independently in statistical models, and clonal partitions are used as the basis for the calculation of diversity metrics, lineage reconstruction and selection analysis. Thus, the spectral clustering-based method here represents an important contribution to repertoire analysis. Availability and implementation: Source code for this method is freely available in the SCOPe (Spectral Clustering for clOne Partitioning) R package in the Immcantation framework: www.immcantation.org under the CC BY-SA 4.0 license. Supplementary information: Supplementary data are available at Bioinformatics online.},
langid = {english},
pmcid = {PMC6022594},
keywords = {B-Lymphocytes,Clone Cells,Cluster Analysis,High-Throughput Nucleotide Sequencing,Models Statistical,Sequence Analysis DNA,Software}
}
@article{nowickaPrognosticSignificanceFCGR2B2021,
title = {Prognostic Significance of {{FCGR2B}} Expression for the Response of {{DLBCL}} Patients to Rituximab or Obinutuzumab Treatment},
author = {Nowicka, Malgorzata and Hilton, Laura K. and Ashton-Key, Margaret and Hargreaves, Chantal E. and Lee, Chern and Foxall, Russell and Carter, Matthew J. and Beers, Stephen A. and Potter, Kathleen N. and Bolen, Christopher R. and Klein, Christian and Knapp, Andrea and Mir, Farheen and Rose-Zerilli, Matthew and Burton, Cathy and Klapper, Wolfram and Scott, David W. and Sehn, Laurie H. and Vitolo, Umberto and Martelli, Maurizio and Trneny, Marek and Rushton, Christopher K. and Slack, Graham W. and Farinha, Pedro and Strefford, Jonathan C. and Oestergaard, Mikkel Z. and Morin, Ryan D. and Cragg, Mark S.},
date = {2021-08-10},
journaltitle = {Blood Advances},
shortjournal = {Blood Adv},
volume = {5},
number = {15},
eprint = {34323958},
eprinttype = {pmid},
pages = {2945--2957},
issn = {2473-9537},
doi = {10.1182/bloodadvances.2021004770},
abstract = {Fc γ receptor IIB (FcγRIIB) is an inhibitory molecule capable of reducing antibody immunotherapy efficacy. We hypothesized its expression could confer resistance in patients with diffuse large B-cell lymphoma (DLBCL) treated with anti-CD20 monoclonal antibody (mAb) chemoimmunotherapy, with outcomes varying depending on mAb (rituximab [R]/obinutuzumab [G]) because of different mechanisms of action. We evaluated correlates between FCGR2B messenger RNA and/or FcγRIIB protein expression and outcomes in 3 de novo DLBCL discovery cohorts treated with R plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) reported by Arthur, Schmitz, and Reddy, and R-CHOP/G-CHOP-treated patients in the GOYA trial (NCT01287741). In the discovery cohorts, higher FCGR2B expression was associated with significantly shorter progression-free survival (PFS; Arthur: hazard ratio [HR], 1.09; 95\% confidence interval [CI], 1.01-1.19; P = .0360; Schmitz: HR, 1.13; 95\% CI, 1.02-1.26; P = .0243). Similar results were observed in GOYA with R-CHOP (HR, 1.26; 95\% CI, 1.00-1.58; P = .0455), but not G-CHOP (HR, 0.91; 95\% CI, 0.69-1.20; P = .50). A nonsignificant trend that high FCGR2B expression favored G-CHOP over R-CHOP was observed (HR, 0.67; 95\% CI, 0.44-1.02; P = .0622); however, low FCGR2B expression favored R-CHOP (HR, 1.58; 95\% CI, 1.00-2.50; P = .0503). In Arthur and GOYA, FCGR2B expression was associated with tumor FcγRIIB expression; correlating with shorter PFS for R-CHOP (HR, 2.17; 95\% CI, 1.04-4.50; P = .0378), but not G-CHOP (HR, 1.37; 95\% CI, 0.66-2.87; P = .3997). This effect was independent of established prognostic biomarkers. High FcγRIIB/FCGR2B expression has prognostic value in R-treated patients with DLBCL and may confer differential responsiveness to R-CHOP/G-CHOP.},
langid = {english},
pmcid = {PMC8361458},
keywords = {Antibodies Monoclonal Humanized,Antineoplastic Combined Chemotherapy Protocols,Cyclophosphamide,Humans,Lymphoma Large B-Cell Diffuse,Morinlab,Prognosis,Receptors IgG,Rituximab,Vincristine}
}
@article{ognibeneHighFrequencyDevelopment,
title = {High Frequency of Development of {{B}} Cell Lymphoproliferation and Diffuse Large {{B}} Cell Lymphoma in {{Dbl}} Knock-in Mice.},
author = {Ognibene, Marzia and Barbieri, Ottavia and Vanni, Cristina and Mastracci, Luca and Astigiano, Simonetta and Emionite, Laura and Salani, Barbara and Fedele, Manuela and Resaz, Roberta and Tenca, Claudya and Fais, Franco and Sabatini, Federica and De Santanna, Amleto and Altruda, Fiorella and Varesio, Luigi and Hirsch, Emilio and Eva, Alessandra},
journaltitle = {Journal of Molecular Medicine (Berlin, Germany)},
volume = {89},
number = {5},
pages = {493--504}
}
@article{ohgamiSTAT3MutationsAre2014,
title = {{{STAT3}} Mutations Are Present in Aggressive {{B-cell}} Lymphomas Including a Subset of Diffuse Large {{B-cell}} Lymphomas with {{CD30}} Expression},
author = {Ohgami, Robert S. and Ma, Lisa and Monabati, Ahmad and Zehnder, James L. and Arber, Daniel A.},
date = {2014-07},
journaltitle = {Haematologica},
shortjournal = {Haematologica},
volume = {99},
number = {7},
eprint = {24837465},
eprinttype = {pmid},
pages = {e105-107},
issn = {1592-8721},
doi = {10.3324/haematol.2013.101543},
langid = {english},
pmcid = {PMC4077094},
keywords = {anaplastic large cell lymphoma,Animals,B-cell lymphoma unclassifiable with features intermediate between DLBCL and Burkitt lymphoma,Bone Marrow Transplantation,CD30,diffuse large B-cell lymphoma,Disease Models Animal,Hematologic Neoplasms,Humans,Mutation,Myeloproliferative Disorders,STAT3,STAT3 Transcription Factor}
}
@article{okamotoIkappaBzetaRegulates172010,
title = {{{IkappaBzeta}} Regulates {{T}}({{H}})17 Development by Cooperating with {{ROR}} Nuclear Receptors.},
author = {Okamoto, Kazuo and Iwai, Yoshiko and Oh-hora, Masatsugu and Yamamoto, Masahiro and Morio, Tomohiro and Aoki, Kazuhiro and Ohya, Keiichi and Jetten, Anton M and Akira, Shizuo and Muta, Tatsushi and Takayanagi, Hiroshi},
date = {2010-04},
journaltitle = {Nature},
volume = {464},
number = {7293},
pages = {1381--1385}
}
@article{okosunRecurrentMTORC1activatingRRAGC2016,
title = {Recurrent {{mTORC1-activating RRAGC}} Mutations in Follicular Lymphoma},
author = {Okosun, Jessica and Wolfson, Rachel L. and Wang, Jun and Araf, Shamzah and Wilkins, Lucy and Castellano, Brian M. and Escudero-Ibarz, Leire and Al Seraihi, Ahad Fahad and Richter, Julia and Bernhart, Stephan H. and Efeyan, Alejo and Iqbal, Sameena and Matthews, Janet and Clear, Andrew and Guerra-Assunção, José Afonso and Bödör, Csaba and Quentmeier, Hilmar and Mansbridge, Christopher and Johnson, Peter and Davies, Andrew and Strefford, Jonathan C. and Packham, Graham and Barrans, Sharon and Jack, Andrew and Du, Ming-Qing and Calaminici, Maria and Lister, T. Andrew and Auer, Rebecca and Montoto, Silvia and Gribben, John G. and Siebert, Reiner and Chelala, Claude and Zoncu, Roberto and Sabatini, David M. and Fitzgibbon, Jude},
date = {2016-02},
journaltitle = {Nature Genetics},
shortjournal = {Nat Genet},
volume = {48},
number = {2},
eprint = {26691987},
eprinttype = {pmid},
pages = {183--188},
issn = {1546-1718},
doi = {10.1038/ng.3473},
abstract = {Follicular lymphoma is an incurable B cell malignancy characterized by the t(14;18) translocation and mutations affecting the epigenome. Although frequent gene mutations in key signaling pathways, including JAK-STAT, NOTCH and NF-κB, have also been defined, the spectrum of these mutations typically overlaps with that in the closely related diffuse large B cell lymphoma (DLBCL). Using a combination of discovery exome and extended targeted sequencing, we identified recurrent somatic mutations in RRAGC uniquely enriched in patients with follicular lymphoma (17\%). More than half of the mutations preferentially co-occurred with mutations in ATP6V1B2 and ATP6AP1, which encode components of the vacuolar H(+)-ATP ATPase (V-ATPase) known to be necessary for amino acid-induced activation of mTORC1. The RagC variants increased raptor binding while rendering mTORC1 signaling resistant to amino acid deprivation. The activating nature of the RRAGC mutations, their existence in the dominant clone and their stability during disease progression support their potential as an excellent candidate for therapeutic targeting.},
langid = {english},
pmcid = {PMC4731318},
keywords = {Amino Acid Sequence,Animals,Humans,Lymphoma Follicular,Mechanistic Target of Rapamycin Complex 1,Molecular Sequence Data,Monomeric GTP-Binding Proteins,Multiprotein Complexes,Mutation,Sequence Homology Amino Acid,TOR Serine-Threonine Kinases}
}
@article{omerVDJbaseAdaptiveImmune2020,
title = {{{VDJbase}}: An Adaptive Immune Receptor Genotype and Haplotype Database},
shorttitle = {{{VDJbase}}},
author = {Omer, Aviv and Shemesh, Or and Peres, Ayelet and Polak, Pazit and Shepherd, Adrian J. and Watson, Corey T. and Boyd, Scott D. and Collins, Andrew M. and Lees, William and Yaari, Gur},
date = {2020-08-01},
journaltitle = {Nucleic Acids Research},
shortjournal = {Nucleic Acids Res.},
volume = {48},
number = {D1},
eprint = {31602484},
eprinttype = {pmid},
pages = {D1051-D1056},
issn = {1362-4962},
doi = {10.1093/nar/gkz872},
abstract = {VDJbase is a publicly available database that offers easy searching of data describing the complete sets of gene sequences (genotypes and haplotypes) inferred from adaptive immune receptor repertoire sequencing datasets. VDJbase is designed to act as a resource that will allow the scientific community to explore the genetic variability of the immunoglobulin (Ig) and T cell receptor (TR) gene loci. It can also assist in the investigation of Ig- and TR-related genetic predispositions to diseases. Our database includes web-based query and online tools to assist in visualization and analysis of the genotype and haplotype data. It enables users to detect those alleles and genes that are significantly over-represented in a particular population, in terms of genotype, haplotype and gene expression. The database website can be freely accessed at https://www.vdjbase.org/, and no login is required. The data and code use creative common licenses and are freely downloadable from https://bitbucket.org/account/user/yaarilab/projects/GPHP.},
langid = {english},
pmcid = {PMC6943044},
keywords = {Computational Biology,Databases Genetic,Genotype,Haplotypes,Humans,Molecular Sequence Annotation,Receptors Antigen B-Cell,Receptors Antigen T-Cell,Receptors Immunologic,Software,Software Design,V(D)J Recombination,Web Browser,Workflow}
}
@article{oricchioGeneticEpigeneticInactivation2017b,
title = {Genetic and Epigenetic Inactivation of {{SESTRIN1}} Controls {{mTORC1}} and Response to {{EZH2}} Inhibition in Follicular Lymphoma},
author = {Oricchio, Elisa and Katanayeva, Natalya and Donaldson, Maria Christine and Sungalee, Stephanie and Pasion, Joyce P. and Béguelin, Wendy and Battistello, Elena and Sanghvi, Viraj R. and Jiang, Man and Jiang, Yanwen and Teater, Matt and Parmigiani, Anita and Budanov, Andrei V. and Chan, Fong Chun and Shah, Sohrab P. and Kridel, Robert and Melnick, Ari M. and Ciriello, Giovanni and Wendel, Hans-Guido},
date = {2017-06-28},
journaltitle = {Science Translational Medicine},
shortjournal = {Sci Transl Med},
volume = {9},
number = {396},
eprint = {28659443},
eprinttype = {pmid},
pages = {eaak9969},
issn = {1946-6242},
doi = {10.1126/scitranslmed.aak9969},
abstract = {Follicular lymphoma (FL) is an incurable form of B cell lymphoma. Genomic studies have cataloged common genetic lesions in FL such as translocation t(14;18), frequent losses of chromosome 6q, and mutations in epigenetic regulators such as EZH2 Using a focused genetic screen, we identified SESTRIN1 as a relevant target of the 6q deletion and demonstrate tumor suppression by SESTRIN1 in vivo. Moreover, SESTRIN1 is a direct target of the lymphoma-specific EZH2 gain-of-function mutation (EZH2Y641X ). SESTRIN1 inactivation disrupts p53-mediated control of mammalian target of rapamycin complex 1 (mTORC1) and enables mRNA translation under genotoxic stress. SESTRIN1 loss represents an alternative to RRAGC mutations that maintain mTORC1 activity under nutrient starvation. The antitumor efficacy of pharmacological EZH2 inhibition depends on SESTRIN1, indicating that mTORC1 control is a critical function of EZH2 in lymphoma. Conversely, EZH2Y641X mutant lymphomas show increased sensitivity to RapaLink-1, a bifunctional mTOR inhibitor. Hence, SESTRIN1 contributes to the genetic and epigenetic control of mTORC1 in lymphoma and influences responses to targeted therapies.},
langid = {english},
pmcid = {PMC5559734},
keywords = {Animals,Chromosome Deletion,Chromosomes Human Pair 6,Enhancer of Zeste Homolog 2 Protein,Epigenesis Genetic,Gene Silencing,Genetic Testing,Genome Human,Heat-Shock Proteins,Humans,Lymphoma Follicular,Mechanistic Target of Rapamycin Complex 1,Mice,Mutation,Protein Biosynthesis,RNA Messenger}
}
@article{oskarsdottirBamHashChecksumProgram2016,
title = {{{BamHash}}: A Checksum Program for Verifying the Integrity of Sequence Data},
shorttitle = {{{BamHash}}},
author = {Óskarsdóttir, Arna and Másson, Gísli and Melsted, Páll},
date = {2016-01-01},
journaltitle = {Bioinformatics},
shortjournal = {Bioinformatics},
volume = {32},
number = {1},
pages = {140--141},
issn = {1367-4803},
doi = {10.1093/bioinformatics/btv539},
url = {https://academic.oup.com/bioinformatics/article/32/1/140/1743564},
urldate = {2019-12-21},
abstract = {Abstract. Summary : Large resequencing projects require a significant amount of storage for raw sequences, as well as alignment files. Because the raw sequence},
langid = {english}
}
@article{ostareck-ledererCSrcmediatedPhosphorylationHnRNP2002,
title = {C-{{Src-mediated}} Phosphorylation of {{hnRNP K}} Drives Translational Activation of Specifically Silenced {{mRNAs}}},
author = {Ostareck-Lederer, Antje and Ostareck, Dirk H. and Cans, Christophe and Neubauer, Gitte and Bomsztyk, Karol and Superti-Furga, Giulio and Hentze, Matthias W.},
date = {2002-07},
journaltitle = {Molecular and Cellular Biology},
shortjournal = {Mol Cell Biol},
volume = {22},
number = {13},
eprint = {12052863},
eprinttype = {pmid},
pages = {4535--4543},
issn = {0270-7306},
doi = {10.1128/MCB.22.13.4535-4543.2002},
abstract = {hnRNPK and hnRNP E1/E2 mediate translational silencing of cellular and viral mRNAs in a differentiation-dependent way by binding to specific regulatory sequences. The translation of 15-lipoxygenase (LOX) mRNA in erythroid precursor cells and of the L2 mRNA of human papilloma virus type 16 (HPV-16) in squamous epithelial cells is silenced when either of these cells is immature and is activated in maturing cells by unknown mechanisms. Here we address the question of how the silenced mRNA can be translationally activated. We show that hnRNP K and the c-Src kinase specifically interact with each other, leading to c-Src activation and tyrosine phosphorylation of hnRNP K in vivo and in vitro. c-Src-mediated phosphorylation reversibly inhibits the binding of hnRNP K to the differentiation control element (DICE) of the LOX mRNA 3' untranslated region in vitro and specifically derepresses the translation of DICE-bearing mRNAs in vivo. Our results establish a novel role of c-Src kinase in translational gene regulation and reveal a mechanism by which silenced mRNAs can be translationally activated.},
langid = {english},
pmcid = {PMC133888},
keywords = {3' Untranslated Regions,Amino Acid Sequence,Arachidonate 15-Lipoxygenase,CSK Tyrosine-Protein Kinase,Gene Silencing,HeLa Cells,Heterogeneous-Nuclear Ribonucleoprotein K,Heterogeneous-Nuclear Ribonucleoproteins,Humans,Molecular Sequence Data,Mutation,Phosphopyruvate Hydratase,Phosphorylation,Protein Biosynthesis,Protein-Tyrosine Kinases,Ribonucleoproteins,RNA Messenger,src Homology Domains,src-Family Kinases,Tyrosine}
}
@article{otaMemoryPathogenicIgE2023,
title = {The Memory of Pathogenic {{IgE}} Is Contained within {{CD23}}+{{IgG1}}+ Memory {{B}} Cells Poised to Switch to {{IgE}} in Food Allergy},
author = {Ota, Miyo and Hoehn, Kenneth B. and Ota, Takayuki and Aranda, Carlos J. and Friedman, Sara and Braga, Weslley F. and Malbari, Alefiyah and Kleinstein, Steven H. and Sicherer, Scott H. and family=Lafaille, given=Maria A. Curotto, prefix=de, useprefix=false},
date = {2023-01-25},
journaltitle = {bioRxiv},
pages = {2023.01.25.525506},
doi = {10.1101/2023.01.25.525506},
url = {https://www.biorxiv.org/content/10.1101/2023.01.25.525506v1},
urldate = {2023-12-16},
abstract = {Food allergy is caused by allergen-specific IgE antibodies but little is known about the B cell memory of persistent IgE responses. Here we describe in human pediatric peanut allergy CD23+IgG1+ memory B cells arising in type 2 responses that contain peanut specific clones and generate IgE cells on activation. These ‘type2-marked’ IgG1+ memory B cells differentially express IL-4/IL-13 regulated genes FCER2/CD23, IL4R, and germline IGHE and carry highly mutated B cell receptors (BCRs). Further, high affinity memory B cells specific for the main peanut allergen Ara h 2 mapped to the population of ‘type2-marked’ IgG1+ memory B cells and included convergent BCRs across different individuals. Our findings indicate that CD23+IgG1+ memory B cells transcribing germline IGHE are a unique memory population containing precursors of pathogenic IgE. One-Sentence Summary We describe a unique population of IgG+ memory B cells poised to switch to IgE that contains high affinity allergen-specific clones in peanut allergy.},
langid = {english}
}
@article{otoshiCytoplasmicAccumulationHeterogeneous2015,
title = {Cytoplasmic {{Accumulation}} of {{Heterogeneous Nuclear Ribonucleoprotein K Strongly Promotes Tumor Invasion}} in {{Renal Cell Carcinoma Cells}}},
author = {Otoshi, Taiyo and Tanaka, Tomoaki and Morimoto, Kazuya and Nakatani, Tatsuya},
date = {2015-12-29},
journaltitle = {PLOS ONE},
shortjournal = {PLOS ONE},
volume = {10},
number = {12},
pages = {e0145769},
publisher = {Public Library of Science},
issn = {1932-6203},
doi = {10.1371/journal.pone.0145769},
url = {https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0145769},
urldate = {2023-01-09},
abstract = {Heterogeneous nuclear ribonucleoprotein (hnRNP) K is a part of the ribonucleoprotein complex which regulates diverse biological events. While overexpression of hnRNP K has been shown to be related to tumorigenesis in several cancers, both the expression patterns and biological mechanisms of hnRNP K in renal cell carcinoma (RCC) cells remain unclear. In this study, we showed that hnRNP K protein was strongly expressed in selected RCC cell lines (ACHN, A498, Caki-1, 786–0), and knock-down of hnRNP K expression by siRNA induced cell growth inhibition and apoptosis. Based on immunohistochemical (IHC) analysis of hnRNP K expression in human clear cell RCC specimens, we demonstrated that there was a significant positive correlation between hnRNP K staining score and tumor aggressiveness (e.g., Fuhrman grade, metastasis). Particularly, the rate of cytoplasmic localization of hnRNP K in primary RCC with distant metastasis was significantly higher than that in RCC without metastasis. Additionally, our results indicated that the cytoplasmic distribution of hnRNP K induced by TGF-β stimulus mainly contributed to TGF-β-triggered tumor cell invasion in RCC cells. Dominant cytoplasmic expression of ectopic hnRNP K markedly suppressed the inhibition of invasion by knock-down of endogenous hnRNP K. The expression level of matrix metalloproteinase protein-2 was decreased by endogenous hnRNP K knock-down, and restored by ectopic hnRNP K. Therefore, hnRNP K may be a key molecule involved in cell motility in RCC cells, and molecular mechanism associated with the subcellular localization of hnRNP K may be a novel target in the treatment of metastatic RCC.},
langid = {english},
keywords = {Cell staining,Cytoplasm,Cytoplasmic staining,Metastasis,Renal cancer,Renal cell carcinoma,Small interfering RNA,Transfection}
}
@article{ottoGeneticLesionsTRAF32012,
title = {Genetic Lesions of the {{TRAF3}} and {{MAP3K14}} Genes in Classical {{Hodgkin}} Lymphoma},
author = {Otto, Claudia and Giefing, Maciej and Massow, Anne and Vater, Inga and Gesk, Stefan and Schlesner, Matthias and Richter, Julia and Klapper, Wolfram and Hansmann, Martin-Leo and Siebert, Reiner and Küppers, Ralf},
date = {2012-06},
journaltitle = {British Journal of Haematology},
shortjournal = {Br J Haematol},
volume = {157},
number = {6},
eprint = {22469134},
eprinttype = {pmid},
pages = {702--708},
issn = {1365-2141},
doi = {10.1111/j.1365-2141.2012.09113.x},
abstract = {Hodgkin and Reed/Sternberg (HRS) cells in classical Hodgkin lymphoma (cHL) show constitutive activation of nuclear factor (NF)-κB. Several genetic lesions contribute to this deregulated NF-κB activity. Here, we analysed two further NF-κB regulators for genetic lesions, the inhibitory factor TRAF3 and the key signalling component of the alternative NF-κB pathway, MAP3K14 (NIK). Single nucleotide polymorphism (SNP) array analysis of cHL cell lines revealed a uniparental disomy of the long arm of chromosome 14 associated with a biallelic deletion of TRAF3 located on this chromosome in cell line U-HO1. Cloning of the deletion breakpoint showed a 123~371 bp deletion. No inactivating mutations of TRAF3 were found in six other cHL cell lines or in microdissected HRS cells from seven cHL. However, in primary cHL samples interphase cytogenetic analyses revealed signal patterns indicating monoallelic deletion of TRAF3 in 3/20 other cases. SNP array analysis revealed a gain of copy number for MAP3K14 in three cHL cell lines. Gains of MAP3K14 were detected in 5/16 cases of primary cHL. In conclusion, in rare instances, HRS cells harbour inactivating mutations of the TRAF3 gene and recurrently show gains of MAP3K14, indicating that more components of NF-κB signalling show genetic lesions in HRS cells than previously known.},
langid = {english},
keywords = {Adolescent,Adult,Aged,Cell Line Tumor,Child,Cytogenetic Analysis,Female,Gene Deletion,Gene Dosage,Hodgkin Disease,Humans,Male,Middle Aged,NF-kappaB-Inducing Kinase,Polymorphism Single Nucleotide,Protein Serine-Threonine Kinases,Proto-Oncogene Proteins,Signal Transduction,TNF Receptor-Associated Factor 3,Trans-Activators}
}
@article{painterCelloforiginDiffuseLarge2019,
title = {Cell-of-Origin in Diffuse Large {{B-cell}} Lymphoma: Findings from the {{UK}}'s Population-Based {{Haematological Malignancy Research Network}}},
shorttitle = {Cell-of-Origin in Diffuse Large {{B-cell}} Lymphoma},
author = {Painter, Daniel and Barrans, Sharon and Lacy, Stuart and Smith, Alexandra and Crouch, Simon and Westhead, David and Sha, Chulin and Patmore, Russell and Tooze, Reuben and Burton, Cathy and Roman, Eve},
date = {2019},
journaltitle = {British Journal of Haematology},
volume = {185},
number = {4},
pages = {781--784},
issn = {1365-2141},
doi = {10.1111/bjh.15619},
url = {https://onlinelibrary.wiley.com/doi/abs/10.1111/bjh.15619},
urldate = {2023-01-16},
langid = {english},
keywords = {epidemiology,gene-expression,prognostic factors,survival}
}
@article{paneaWholeGenomeLandscape2019,
title = {The Whole Genome Landscape of {{Burkitt}} Lymphoma Subtypes.},
author = {Panea, R. and Love, C. and Shingleton, Jennifer R. and Reddy, Anupama and Bailey, J. and Moormann, A. and Otieno, J. and Ong'echa, J. and Oduor, C. and Schroêder, K. and Masalu, N. and Chao, N. and Agajanian, M. and Major, M. and Fedoriw, Y. and Richards, K. and Rymkiewicz, G. and Miles, R. and Alobeid, B. and Bhagat, G. and Flowers, C. and Ondrejka, S. and Hsi, E. and Choi, W. and Au-Yeung, R. and Hartmann, W. and Lenz, G. and Meyerson, H. and Lin, Yen-Yu and Zhuang, Y. and Luftig, M. and Waldrop, A. and Dave, Tushar and Thakkar, D. and Sahay, Harshit and Li, Guojie and Palus, B. and Seshadri, V. and Kim, S. and Gascoyne, R. and Levy, S. and Mukhopadhyay, Minerva and Dunson, D. and Dave, S.},
date = {2019},
journaltitle = {Blood},
shortjournal = {Blood},
doi = {10.1182/blood.2019001880}
}
@article{pararajalingamCodingNoncodingDrivers2020,
title = {Coding and Noncoding Drivers of Mantle Cell Lymphoma Identified through Exome and Genome Sequencing},
author = {Pararajalingam, Prasath and Coyle, Krysta M. and Arthur, Sarah E. and Thomas, Nicole and Alcaide, Miguel and Meissner, Barbara and Boyle, Merrill and Qureshi, Quratulain and Grande, Bruno M. and Rushton, Christopher and Slack, Graham W. and Mungall, Andrew J. and Tam, Constantine S. and Agarwal, Rishu and Dawson, Sarah-Jane and Lenz, Georg and Balasubramanian, Sriram and Gascoyne, Randy D. and Steidl, Christian and Connors, Joseph and Villa, Diego and Audas, Timothy E. and Marra, Marco A. and Johnson, Nathalie A. and Scott, David W. and Morin, Ryan D.},
date = {2020-07-30},
journaltitle = {Blood},
shortjournal = {Blood},
volume = {136},
number = {5},
eprint = {32160292},
eprinttype = {pmid},
pages = {572--584},
issn = {1528-0020},
doi = {10.1182/blood.2019002385},
abstract = {Mantle cell lymphoma (MCL) is an uncommon B-cell non-Hodgkin lymphoma (NHL) that is incurable with standard therapies. The genetic drivers of this cancer have not been firmly established, and the features that contribute to differences in clinical course remain limited. To extend our understanding of the biological pathways involved in this malignancy, we performed a large-scale genomic analysis of MCL using data from 51 exomes and 34 genomes alongside previously published exome cohorts. To confirm our findings, we resequenced the genes identified in the exome cohort in 191 MCL tumors, each having clinical follow-up data. We confirmed the prognostic association of TP53 and NOTCH1 mutations. Our sequencing revealed novel recurrent noncoding mutations surrounding a single exon of the HNRNPH1gene. In RNA-seq data from 103 of these cases, MCL tumors with these mutations had a distinct imbalance of HNRNPH1 isoforms. This altered splicing of HNRNPH1 was associated with inferior outcomes in MCL and showed a significant increase in protein expression by immunohistochemistry. We describe a functional role for these recurrent noncoding mutations in disrupting an autoregulatory feedback mechanism, thereby deregulating HNRNPH1 protein expression. Taken together, these data strongly imply a role for aberrant regulation of messenger RNA processing in MCL pathobiology.},
langid = {english},
pmcid = {PMC7440974},
keywords = {Adult,Aged,Aged 80 and over,Female,Genetic Predisposition to Disease,Genotype,Heterogeneous-Nuclear Ribonucleoproteins,Humans,Lymphoma Mantle-Cell,Male,Middle Aged,Morinlab,Mutation,Whole Genome Sequencing}
}
@article{parekhTherapeuticTargetingBCL6,
title = {Therapeutic Targeting of the {{BCL6}} Oncogene for Diffuse Large {{B-cell}} Lymphomas},
author = {Parekh, Samir and Privé, Gilbert and Melnick, Ari},
journaltitle = {Leuk lymphoma},
volume = {49},
number = {5},
pages = {874--882}
}
@article{parkHeterogeneousNuclearRibonucleoprotein2017,
title = {Heterogeneous {{Nuclear Ribonucleoprotein A2B1 Exerts}} a {{Regulatory Role}} in {{Lipopolysaccharide-stimulated 38B9 B Cell Activation}}},
author = {Park, Jisang and Choe, Chung-Hyeon and Kim, Ju and Yang, Jing Shian and Kim, Jin Hyun and Jang, Hyonseok and Jang, Yong-Suk},
date = {2017-12},
journaltitle = {Immune Network},
shortjournal = {Immune Netw},
volume = {17},
number = {6},
eprint = {29302256},
eprinttype = {pmid},
pages = {437--450},
issn = {1598-2629},
doi = {10.4110/in.2017.17.6.437},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5746613/},
urldate = {2022-10-06},
abstract = {Major histocompatibility complex (MHC) class II molecules, which are recognized for their primary function of presenting an antigen to the T cell receptor, are involved in various signaling pathways in B cell activation. We identified heterogeneous nuclear ribonucleoprotein (hnRNP) A2B1 as an MHC class II molecule-associated protein involved in MHC class II-mediated signal transduction in lipopolysaccharide (LPS)-stimulated 38B9 B cells. Although the function of hnRNP A2B1 in the nucleus is primarily known, the level of hnRNP A2B1 in the cytoplasm was increased in LPS-stimulated 38B9 cells, while it was not detected in the cytoplasm of non-treated 38B9 cells. The silencing of hnRNP A2B1 expression using siRNA disturbed B cell maturation by regulation of mitogen-activated protein kinase signaling, NF-κB activation, and protein kinase B activation. These results suggest that hnRNP A2B1 is associated with MHC class II molecules and is involved in B cell activation signaling pathways in LPS-stimulated 38B9 cells.},
pmcid = {PMC5746613}
}
@article{parkInteractionBCL2Interleukin102009,
title = {Interaction between {{BCL2}} and {{Interleukin-10 Gene Polymorphisms Alter Outcomes}} of {{Diffuse Large B-Cell Lymphoma}} Following {{Rituximab Plus CHOP Chemotherapy}}},
author = {Park, Y H and Sohn, S K and Kim, J G and Lee, M-H and Song, H S and Kim, M K and Jung, J S and Lee, J-J and Kim, H J and Kim, D H},
date = {2009-03},
journaltitle = {Clin Cancer Res},
volume = {15},
number = {6},
pages = {2107--2115}
}
@article{paronettoEwingSarcomaProtein2011,
title = {The {{Ewing Sarcoma Protein Regulates DNA Damage-Induced Alternative Splicing}}},
author = {Paronetto, Maria Paola and Miñana, Belén and Valcárcel, Juan},
date = {2011-08-05},
journaltitle = {Molecular Cell},
shortjournal = {Molecular Cell},
volume = {43},
number = {3},
eprint = {21816343},
eprinttype = {pmid},
pages = {353--368},
issn = {1097-2765},
doi = {10.1016/j.molcel.2011.05.035},
url = {https://www.cell.com/molecular-cell/abstract/S1097-2765(11)00462-X},
urldate = {2019-12-21},
langid = {english}
}
@article{parryWholeExomeSequencing2013,
title = {Whole Exome Sequencing Identifies Novel Recurrently Mutated Genes in Patients with Splenic Marginal Zone Lymphoma},
author = {Parry, Marina and Rose-Zerilli, Matthew J. J. and Gibson, Jane and Ennis, Sarah and Walewska, Renata and Forster, Jade and Parker, Helen and Davis, Zadie and Gardiner, Anne and Collins, Andrew and Oscier, David G. and Strefford, Jonathan C.},
date = {2013},
journaltitle = {PloS One},
shortjournal = {PLoS One},
volume = {8},
number = {12},
eprint = {24349473},
eprinttype = {pmid},
pages = {e83244},
issn = {1932-6203},
doi = {10.1371/journal.pone.0083244},
abstract = {The pathogenesis of splenic marginal zone lymphoma (SMZL) remains largely unknown. Recent high-throughput sequencing studies have identified recurrent mutations in key pathways, most notably NOTCH2 mutations in {$>$}25\% of patients. These studies are based on small, heterogeneous discovery cohorts, and therefore only captured a fraction of the lesions present in the SMZL genome. To identify further novel pathogenic mutations within related biochemical pathways, we applied whole exome sequencing (WES) and copy number (CN) analysis to a biologically and clinically homogeneous cohort of seven SMZL patients with 7q abnormalities and IGHV1-2*04 gene usage. We identified 173 somatic non-silent variants, affecting 160 distinct genes. In additional to providing independent validation of the presence of mutation in several previously reported genes (NOTCH2, TNFAIP3, MAP3K14, MLL2 and SPEN), our study defined eight additional recurrently mutated genes in SMZL; these genes are CREBBP, CBFA2T3, AMOTL1, FAT4, FBXO11, PLA2G4D, TRRAP and USH2A. By integrating our WES and CN data we identified three mutated putative candidate genes targeted by 7q deletions (CUL1, EZH2 and FLNC), with FLNC positioned within the well-characterized 7q minimally deleted region. Taken together, this work expands the reported directory of recurrently mutated cancer genes in this disease, thereby expanding our understanding of SMZL pathogenesis. Ultimately, this work will help to establish a stratified approach to care including the possibility of targeted therapy.},
langid = {english},
pmcid = {PMC3862727},
keywords = {Chromosomes Human Pair 7,DNA Mutational Analysis,Exome,Female,Humans,Lymphoma B-Cell Marginal Zone,Male,Mutation,Neoplasm Proteins,Splenic Neoplasms}
}
@article{pasqualucciAnalysisCodingGenome2011,
title = {Analysis of the Coding Genome of Diffuse Large {{B-cell}} Lymphoma},
author = {Pasqualucci, Laura and Trifonov, Vladimir and Fabbri, Giulia and Ma, Jing and Rossi, Davide and Chiarenza, Annalisa and Wells, Victoria A. and Grunn, Adina and Messina, Monica and Elliot, Oliver and Chan, Joseph and Bhagat, Govind and Chadburn, Amy and Gaidano, Gianluca and Mullighan, Charles G. and Rabadan, Raul and Dalla-Favera, Riccardo},
date = {2011-07-31},
journaltitle = {Nature Genetics},
shortjournal = {Nat Genet},
volume = {43},
number = {9},
eprint = {21804550},
eprinttype = {pmid},
pages = {830--837},
issn = {1546-1718},
doi = {10.1038/ng.892},
abstract = {Diffuse large B-cell lymphoma (DLBCL) is the most common form of human lymphoma. Although a number of structural alterations have been associated with the pathogenesis of this malignancy, the full spectrum of genetic lesions that are present in the DLBCL genome, and therefore the identity of dysregulated cellular pathways, remains unknown. By combining next-generation sequencing and copy number analysis, we show that the DLBCL coding genome contains, on average, more than 30 clonally represented gene alterations per case. This analysis also revealed mutations in genes not previously implicated in DLBCL pathogenesis, including those regulating chromatin methylation (MLL2; 24\% of samples) and immune recognition by T cells. These results provide initial data on the complexity of the DLBCL coding genome and identify novel dysregulated pathways underlying its pathogenesis.},
langid = {english},
pmcid = {PMC3297422},
keywords = {Chromatin,Diploidy,DNA Mutational Analysis,Gene Dosage,Gene Expression Regulation Leukemic,Genome Human,Germinal Center,Humans,Lymphoma Large B-Cell Diffuse,Methylation,Neoplasm Recurrence Local,Point Mutation,Polymorphism Single Nucleotide,T-Lymphocytes}
}
@article{pasqualucciGeneticLandscapeDiffuse,
title = {The {{Genetic Landscape}} of {{Diffuse Large B-Cell Lymphoma}}},
author = {Pasqualucci, Laura and Dalla-Favera, Riccardo},
journaltitle = {Seminars in Hematology},
volume = {52},
number = {2},
pages = {67--76}
}
@article{pasqualucciHypermutationMultipleProtooncogenes,
title = {Hypermutation of Multiple Proto-Oncogenes in {{B-cell}} Diffuse Large-Cell Lymphomas},
author = {Pasqualucci, L and Neumeister, P and Stoorvogel, W and Nanjangud, G and Chaganti, R and Kuppers, R and Dalla-Favera, R},
journaltitle = {Nature},
volume = {412},
number = {6844},
pages = {341--346}
}
@article{pasqualucciHypermutationMultipleProtooncogenes2001,
title = {Hypermutation of Multiple Proto-Oncogenes in {{B-cell}} Diffuse Large-Cell Lymphomas},
author = {Pasqualucci, L. and Neumeister, P. and Goossens, T. and Nanjangud, G. and Chaganti, R. S. and Küppers, R. and Dalla-Favera, R.},
date = {2001-07-19},
journaltitle = {Nature},
shortjournal = {Nature},
volume = {412},
number = {6844},
eprint = {11460166},
eprinttype = {pmid},
pages = {341--346},
issn = {0028-0836},
doi = {10.1038/35085588},
abstract = {Genomic instability promotes tumorigenesis and can occur through various mechanisms, including defective segregation of chromosomes or inactivation of DNA mismatch repair. Although B-cell lymphomas are associated with chromosomal translocations that deregulate oncogene expression, a mechanism for genome-wide instability during lymphomagenesis has not been described. During B-cell development, the immunoglobulin variable (V) region genes are subject to somatic hypermutation in germinal-centre B cells. Here we report that an aberrant hypermutation activity targets multiple loci, including the proto-oncogenes PIM1, MYC, RhoH/TTF (ARHH) and PAX5, in more than 50\% of diffuse large-cell lymphomas (DLCLs), which are tumours derived from germinal centres. Mutations are distributed in the 5' untranslated or coding sequences, are independent of chromosomal translocations, and share features typical of V-region-associated somatic hypermutation. In contrast to mutations in V regions, however, these mutations are not detectable in normal germinal-centre B cells or in other germinal-centre-derived lymphomas, suggesting a DLCL-associated malfunction of somatic hypermutation. Intriguingly, the four hypermutable genes are susceptible to chromosomal translocations in the same region, consistent with a role for hypermutation in generating translocations by DNA double-strand breaks. By mutating multiple genes, and possibly by favouring chromosomal translocations, aberrant hypermutation may represent the major contributor to lymphomagenesis.},
langid = {english},
keywords = {B-Lymphocytes,DNA Mutational Analysis,DNA-Binding Proteins,Genes myc,Germinal Center,Humans,Lymphoma B-Cell,Lymphoma Large B-Cell Diffuse,Molecular Sequence Data,Mutation,PAX5 Transcription Factor,Proteins,Proto-Oncogenes,Transcription Factors}
}
@article{pasqualucciInactivatingMutationsAcetyltransferase2011,
title = {Inactivating Mutations of Acetyltransferase Genes in {{B-cell}} Lymphoma},
author = {Pasqualucci, Laura and Dominguez-Sola, David and Chiarenza, Annalisa and Fabbri, Giulia and Grunn, Adina and Trifonov, Vladimir and Kasper, Lawryn H. and Lerach, Stephanie and Tang, Hongyan and Ma, Jing and Rossi, Davide and Chadburn, Amy and Murty, Vundavalli V. and Mullighan, Charles G. and Gaidano, Gianluca and Rabadan, Raul and Brindle, Paul K. and Dalla-Favera, Riccardo},
date = {2011-03-10},
journaltitle = {Nature},
shortjournal = {Nature},
volume = {471},
number = {7337},
eprint = {21390126},
eprinttype = {pmid},
pages = {189--195},
issn = {1476-4687},
doi = {10.1038/nature09730},
abstract = {B-cell non-Hodgkin's lymphoma comprises biologically and clinically distinct diseases the pathogenesis of which is associated with genetic lesions affecting oncogenes and tumour-suppressor genes. We report here that the two most common types--follicular lymphoma and diffuse large B-cell lymphoma--harbour frequent structural alterations inactivating CREBBP and, more rarely, EP300, two highly related histone and non-histone acetyltransferases (HATs) that act as transcriptional co-activators in multiple signalling pathways. Overall, about 39\% of diffuse large B-cell lymphoma and 41\% of follicular lymphoma cases display genomic deletions and/or somatic mutations that remove or inactivate the HAT coding domain of these two genes. These lesions usually affect one allele, suggesting that reduction in HAT dosage is important for lymphomagenesis. We demonstrate specific defects in acetylation-mediated inactivation of the BCL6 oncoprotein and activation of the p53 tumour suppressor. These results identify CREBBP/EP300 mutations as a major pathogenetic mechanism shared by common forms of B-cell non-Hodgkin's lymphoma, with direct implications for the use of drugs targeting acetylation/deacetylation mechanisms.},
langid = {english},
pmcid = {PMC3271441},
keywords = {Acetyl Coenzyme A,Acetylation,Acetyltransferases,Animals,Base Sequence,Cells Cultured,CREB-Binding Protein,DNA-Binding Proteins,E1A-Associated p300 Protein,Gene Expression Regulation Neoplastic,HEK293 Cells,Histone Acetyltransferases,Humans,Lymphoma B-Cell,Lymphoma Follicular,Lymphoma Large B-Cell Diffuse,Mice,Mutation,Mutation Missense,Polymorphism Single Nucleotide,Protein Binding,Protein Structure Tertiary,Proto-Oncogene Proteins c-bcl-6,Recurrence,Sequence Deletion,Tumor Suppressor Protein p53}
}
@article{pasqualucciInactivationPRDM1BLIMP12006,
title = {Inactivation of the {{PRDM1}}/{{BLIMP1}} Gene in Diffuse Large {{B}} Cell Lymphoma.},
author = {Pasqualucci, Laura and Compagno, Mara and Houldsworth, Jane and Monti, Stefano and Grunn, Adina and Nandula, Subhadra V and Aster, Jon C and Murty, Vundavally V and Shipp, Margaret A and Dalla-Favera, Riccardo},
date = {2006-02},
journaltitle = {J Exp Med},
volume = {203},
number = {2},
pages = {311--317}
}
@article{pasqualucciMutationsBCL6Protooncogene2003,
title = {Mutations of the {{BCL6}} Proto-Oncogene Disrupt Its Negative Autoregulation in Diffuse Large {{B-cell}} Lymphoma},
author = {Pasqualucci, Laura and Migliazza, Anna and Basso, Katia and Houldsworth, Jane and Chaganti, R S K and Dalla-Favera, Riccardo},
date = {2003-04},
journaltitle = {Blood},
volume = {101},
number = {8},
pages = {2914--2923}
}
@article{patroSalmonProvidesFast2017,
title = {Salmon Provides Fast and Bias-Aware Quantification of Transcript Expression},
author = {Patro, Rob and Duggal, Geet and Love, Michael I. and Irizarry, Rafael A. and Kingsford, Carl},
date = {2017-04},
journaltitle = {Nature Methods},
shortjournal = {Nat. Methods},
volume = {14},
number = {4},
eprint = {28263959},
eprinttype = {pmid},
pages = {417--419},
issn = {1548-7105},
doi = {10.1038/nmeth.4197},
abstract = {We introduce Salmon, a lightweight method for quantifying transcript abundance from RNA-seq reads. Salmon combines a new dual-phase parallel inference algorithm and feature-rich bias models with an ultra-fast read mapping procedure. It is the first transcriptome-wide quantifier to correct for fragment GC-content bias, which, as we demonstrate here, substantially improves the accuracy of abundance estimates and the sensitivity of subsequent differential expression analysis.},
langid = {english},
pmcid = {PMC5600148},
keywords = {Algorithms,Base Composition,Bayes Theorem,Gene Expression Profiling,Sequence Analysis RNA}
}
@article{pengHnRNPKPromotesGastric2019,
title = {{{hnRNPK}} Promotes Gastric Tumorigenesis through Regulating {{CD44E}} Alternative Splicing},
author = {Peng, Wei-zhao and Liu, Ji-xi and Li, Chao-feng and Ma, Ren and Jie, Jian-zheng},
date = {2019-12-12},
journaltitle = {Cancer Cell International},
shortjournal = {Cancer Cell International},
volume = {19},
number = {1},
pages = {335},
issn = {1475-2867},
doi = {10.1186/s12935-019-1020-x},
url = {https://doi.org/10.1186/s12935-019-1020-x},
urldate = {2022-09-22},
abstract = {The high prevalence of alternative splicing among genes implies the importance of genomic complexity in regulating normal physiological processes and diseases such as gastric cancer (GC). The standard form of stem cell marker CD44 (CD44S) and its alternatives with additional exons are reported to play important roles in multiple types of tumors, but the regulation mechanism of CD44 alternative splicing is not fully understood.},
keywords = {Alternative splicing,CD44E,Gastric cancer,hnRNPK,SRSF1}
}
@article{peperzakFunctionalDisparitiesBCL22017,
title = {Functional Disparities among {{BCL-2}} Members in Tonsillar and Leukemic {{B-cell}} Subsets Assessed by {{BH3-mimetic}} Profiling},
author = {Peperzak, Victor and Slinger, Erik and Ter Burg, Johanna and Eldering, Eric},
date = {2017-01},
journaltitle = {Cell Death \& Differentiation},
shortjournal = {Cell Death Differ},
volume = {24},
number = {1},
pages = {111--119},
publisher = {Nature Publishing Group},
issn = {1476-5403},
doi = {10.1038/cdd.2016.105},
url = {https://www.nature.com/articles/cdd2016105},
urldate = {2022-10-06},
abstract = {For successful treatment of malignant B-cells it is crucial to understand intrinsic survival requirements in relation to their normal progenitors. Long-lived humoral immunity as well as most B-cell malignancies, originate in the germinal center (GC). Murine GC B-cells depend on pro-survival protein MCL-1, but not BCL-XL. In contrast, naive and memory B-cells depend on BCL-2, but not BCL-XL or MCL-1. For human B-cell subsets, the functional relationships among BCL-2 members are unclear, and also if and how they shift after malignant transformation. We here dissect these aspects in human tonsil and primary leukemia (CLL) cells by single and combined treatment with novel, highly specific BH3-mimetics. We found that MCL-1 expression in GC B-cells is regulated post-translationally and its importance is highlighted by preferential binding to pro-apoptotic BIM. In contrast, BCL-XL is transcriptionally induced and binds solely to weak sensitizer BIK, potentially explaining why BCL-XL is not required for GC B-cell survival. Using novel BH3-mimetics, we found that naive and memory B-cells depend on BCL-2, GC cells predominantly on MCL-1, whereas plasma cells need both BCL-XL and MCL-1 for survival. CLL cells switch from highly sensitive for BCL-2 inhibition to resistant after CD40-stimulation. However, combined inhibition of BCL-2, plus BCL-XL or MCL-1 effectively kills these cells, thus exposing a weakness that may be therapeutically useful. These general principles offer important clues for designing treatment strategies for B-cell malignancies.},
issue = {1},
langid = {english},
keywords = {Cell death and immune response,Oncogenes}
}
@article{pereiraRNABindingProteinsCancer2017,
title = {{{RNA-Binding Proteins}} in {{Cancer}}: {{Old Players}} and {{New Actors}}},
shorttitle = {{{RNA-Binding Proteins}} in {{Cancer}}},
author = {Pereira, Bruno and Billaud, Marc and Almeida, Raquel},
date = {2017-07},
journaltitle = {Trends in Cancer},
shortjournal = {Trends Cancer},
volume = {3},
number = {7},
eprint = {28718405},
eprinttype = {pmid},
pages = {506--528},
issn = {2405-8025},
doi = {10.1016/j.trecan.2017.05.003},
abstract = {RNA-binding proteins (RBPs) are key players in post-transcriptional events. The combination of versatility of their RNA-binding domains with structural flexibility enables RBPs to control the metabolism of a large array of transcripts. Perturbations in RBP-RNA networks activity have been causally associated with cancer development, but the rational framework describing these contributions remains fragmented. We review here the evidence that RBPs modulate multiple cancer traits, emphasize their functional diversity, and assess future trends in the study of RBPs in cancer.},
langid = {english},
keywords = {Alternative Splicing,Animals,Antineoplastic Agents,Biomarkers Tumor,cancer,Carcinogenesis,Disease Progression,Gene Regulatory Networks,Humans,Molecular Targeted Therapy,Neoplasm Invasiveness,Neoplasms,post-transcriptional regulation,ribonucleoprotein complex,RNA,RNA Processing Post-Transcriptional,RNA-Binding Motifs,RNA-binding protein,RNA-Binding Proteins}
}
@article{pereverzevMethodQuantitativeAnalysis2015,
title = {Method for Quantitative Analysis of Nonsense-Mediated {{mRNA}} Decay at the Single Cell Level},
author = {Pereverzev, Anton P. and Gurskaya, Nadya G. and Ermakova, Galina V. and Kudryavtseva, Elena I. and Markina, Nadezhda M. and Kotlobay, Alexey A. and Lukyanov, Sergey A. and Zaraisky, Andrey G. and Lukyanov, Konstantin A.},
date = {2015-01-12},
journaltitle = {Scientific Reports},
volume = {5},
number = {1},
pages = {1--10},
issn = {2045-2322},
doi = {10.1038/srep07729},
url = {https://www.nature.com/articles/srep07729},
urldate = {2019-12-21},
abstract = {Nonsense-mediated mRNA decay (NMD) is a ubiquitous mechanism of degradation of transcripts with a premature termination codon. NMD eliminates aberrant mRNA species derived from sources of genetic variation such as gene mutations, alternative splicing and DNA rearrangements in immune cells. In addition, recent data suggest that NMD is an important mechanism of global gene expression regulation. Here, we describe new reporters to quantify NMD activity at the single cell level using fluorescent proteins of two colors: green TagGFP2 and far-red Katushka. TagGFP2 was encoded by mRNA targeted to either the splicing-dependent or the long 3'UTR-dependent NMD pathway. Katushka was used as an expression level control. Comparison of the fluorescence intensities of cells expressing these reporters and cells expressing TagGFP2 and Katushka from corresponding control NMD-independent vectors allowed for the assessment of NMD activity at the single cell level using fluorescence microscopy and flow cytometry. The proposed reporter system was successfully tested in several mammalian cell lines and in transgenic Xenopus embryos.},
langid = {english}
}
@article{perez-bozaHnRNPA2B1InhibitsExosomal2020,
title = {{{hnRNPA2B1}} Inhibits the Exosomal Export of {{miR-503}} in Endothelial Cells},
author = {Pérez-Boza, Jennifer and Boeckx, Amandine and Lion, Michele and Dequiedt, Franck and Struman, Ingrid},
date = {2020-11-01},
journaltitle = {Cellular and Molecular Life Sciences},
shortjournal = {Cell. Mol. Life Sci.},
volume = {77},
number = {21},
pages = {4413--4428},
issn = {1420-9071},
doi = {10.1007/s00018-019-03425-6},
url = {https://doi.org/10.1007/s00018-019-03425-6},
urldate = {2022-10-04},
abstract = {The chemotherapeutic drug epirubicin increases the exosomal export of miR-503 in endothelial cells. To understand the mechanisms behind this process, we transfected endothelial cells with miR-503 carrying a biotin tag. Then, we pulled-down the proteins interacting with miR-503 and studied their role in microRNA exosomal export. A total of four different binding partners were identified by mass spectrometry and validated by western blotting and negative controls, among them ANXA2 and hnRNPA2B1. Using knock-down systems combined with pull-down analysis, we determined that epirubicin mediates the export of miR-503 by disrupting the interaction between hnRNPA2B1 and miR-503. Then, both ANXA2 and miR-503 are sorted into exosomes while hnRNPA2B1 is relocated into the nucleus. The combination of these processes culminates in the increased export of miR-503. These results suggest, for the first time, that RNA-binding proteins can negatively regulate the exosomal sorting of microRNAs.},
langid = {english},
keywords = {EVs,Exosomal export,Exosomes,MicroRNAs,RNA-binding proteins}
}
@article{perteaStringTieEnablesImproved2015,
title = {{{StringTie}} Enables Improved Reconstruction of a Transcriptome from {{RNA-seq}} Reads},
author = {Pertea, Mihaela and Pertea, Geo M. and Antonescu, Corina M. and Chang, Tsung-Cheng and Mendell, Joshua T. and Salzberg, Steven L.},
date = {2015-03},
journaltitle = {Nature Biotechnology},
shortjournal = {Nat Biotechnol},
volume = {33},
number = {3},
pages = {290--295},
publisher = {Nature Publishing Group},
issn = {1546-1696},
doi = {10.1038/nbt.3122},
url = {https://www.nature.com/articles/nbt.3122},
urldate = {2021-11-30},
abstract = {Using a network flow algorithm from optimization theory enables improved assembly of transcriptomes from RNA-seq reads.},
issue = {3},
langid = {english},
keywords = {Genome assembly algorithms,Transcriptomics},
annotation = {Bandiera\_abtest: a\\
Cg\_type: Nature Research Journals\\
Primary\_atype: Research\\
Subject\_term: Genome assembly algorithms;Transcriptomics\\
Subject\_term\_id: genome-assembly-algorithms;transcriptomics}
}
@article{pervouchineIntegrativeTranscriptomicAnalysis2019,
title = {Integrative Transcriptomic Analysis Suggests New Autoregulatory Splicing Events Coupled with Nonsense-Mediated {{mRNA}} Decay},
author = {Pervouchine, Dmitri and Popov, Yaroslav and Berry, Andy and Borsari, Beatrice and Frankish, Adam and Guigó, Roderic},
date = {2019-04-06},
journaltitle = {Nucleic Acids Research},
shortjournal = {Nucleic Acids Res.},
volume = {47},
number = {10},
eprint = {30916337},
eprinttype = {pmid},
pages = {5293--5306},
issn = {1362-4962},
doi = {10.1093/nar/gkz193},
abstract = {Nonsense-mediated decay (NMD) is a eukaryotic mRNA surveillance system that selectively degrades transcripts with premature termination codons (PTC). Many RNA-binding proteins (RBP) regulate their expression levels by a negative feedback loop, in which RBP binds its own pre-mRNA and causes alternative splicing to introduce a PTC. We present a bioinformatic analysis integrating three data sources, eCLIP assays for a large RBP panel, shRNA inactivation of NMD pathway, and shRNA-depletion of RBPs followed by RNA-seq, to identify novel such autoregulatory feedback loops. We show that RBPs frequently bind their own pre-mRNAs, their exons respond prominently to NMD pathway disruption, and that the responding exons are enriched with nearby eCLIP peaks. We confirm previously proposed models of autoregulation in SRSF7 and U2AF1 genes and present two novel models, in which (i) SFPQ binds its mRNA and promotes switching to an alternative distal 3'-UTR that is targeted by NMD, and (ii) RPS3 binding activates a poison 5'-splice site in its pre-mRNA that leads to a frame shift and degradation by NMD. We also suggest specific splicing events that could be implicated in autoregulatory feedback loops in RBM39, HNRNPM, and U2AF2 genes. The results are available through a UCSC Genome Browser track hub.},
langid = {english},
pmcid = {PMC6547761},
keywords = {3' Untranslated Regions,Alternative Splicing,Codon Nonsense,Computational Biology,Exons,Frameshift Mutation,Heterogeneous-Nuclear Ribonucleoprotein Group M,Humans,Nonsense Mediated mRNA Decay,Nuclear Proteins,RNA Messenger,RNA Precursors,RNA Small Interfering,RNA Splicing,RNA-Binding Proteins,Serine-Arginine Splicing Factors,Spliceosomes,Splicing Factor U2AF,Transcriptome}
}
@article{petereitPipelineAutomationSnakemake2022,
title = {Pipeline {{Automation}} via {{Snakemake}}},
author = {Petereit, Jakob},
date = {2022},
journaltitle = {Methods in Molecular Biology (Clifton, N.J.)},
shortjournal = {Methods Mol Biol},
volume = {2443},
eprint = {35037206},
eprinttype = {pmid},
pages = {181--196},
issn = {1940-6029},
doi = {10.1007/978-1-0716-2067-0_9},
abstract = {With third generation DNA sequencing and a general reduction of sequencing costs, the production of bioinformatic data has become easier than ever. Several pipeline automation tools have emerged to ease data processing through a multitude of steps. Here, we describe the setup and use of Snakemake, a pipeline automation tool derived from GNU MAKE.},
langid = {english},
keywords = {Bioinformatics,Bowtie2 alignments,fastQC,Pipeline,Snakemake,Trimming}
}
@article{petersonElucidatingFalsenegativeMYC2019,
title = {Elucidating a False-Negative {{MYC}} Break-Apart Fluorescence in Situ Hybridization Probe Study by next-Generation Sequencing in a Patient with High-Grade {{B-cell}} Lymphoma with {{IGH}}/{{MYC}} and {{IGH}}/{{BCL2}} Rearrangements},
author = {Peterson, Jess F. and Pitel, Beth A. and Smoley, Stephanie A. and Vasmatzis, George and Smadbeck, James B. and Greipp, Patricia T. and Ketterling, Rhett P. and Macon, William R. and Baughn, Linda B.},
date = {2019-06},
journaltitle = {Cold Spring Harbor Molecular Case Studies},
shortjournal = {Cold Spring Harb Mol Case Stud},
volume = {5},
number = {3},
eprint = {31160360},
eprinttype = {pmid},
pages = {a004077},
issn = {2373-2873},
doi = {10.1101/mcs.a004077},
abstract = {The identification of MYC rearrangements in several mature B-cell neoplasms is critical for diagnostic and prognostic purposes. Commercially available fluorescence in situ hybridization (FISH) probe sets, including IGH/MYC dual-color dual-fusion (D-FISH) and MYC break-apart probes (BAPs), serve as the primary methodology utilized to detect MYC rearrangements. However, performing either IGH/MYC D-FISH or MYC BAP FISH studies in isolation has been reported to result in false-negative results because of the complex nature of 8q24 rearrangements involving the MYC gene region. We report a 60-yr-old male with newly diagnosed high-grade B-cell lymphoma with a negative MYC BAP study, but with positive BCL2 and BCL6 BAP studies. Per our current laboratory algorithm to concurrently interrogate the MYC gene region with both MYC BAP and IGH/MYC D-FISH probe sets, we performed IGH/MYC D-FISH studies and detected an IGH/MYC fusion. To further characterize the discrepant MYC results obtained by FISH, a next-generation sequencing strategy, mate-pair sequencing (MPseq), was performed and revealed a small insertion (∼200 kb) of the IGH locus downstream from the MYC gene that was undetectable by MYC BAP studies. This case highlights the importance of utilizing both IGH/MYC D-FISH and MYC BAP sets to detect potential cryptic MYC rearrangements and also demonstrates the power of MPseq to characterize complex structural rearrangements and copy-number abnormalities unappreciable by FISH.},
langid = {english},
pmcid = {PMC6549546},
keywords = {B-cell lymphoma}
}
@article{pham-ledardHighFrequencyClinical,
title = {High Frequency and Clinical Prognostic Value of {{MYD88 L265P}} Mutation in Primary Cutaneous Diffuse Large {{B-cell}} Lymphoma, Leg-Type.},
author = {Pham-Ledard, Anne and Beylot-Barry, Marie and Barbe, Coralie and Leduc, Marion and Petrella, Tony and Vergier, Béatrice and Martinez, Fabian and Cappellen, David and Merlio, Jean-Philippe and Grange, Florent},
journaltitle = {JAMA dermatology},
volume = {150},
number = {11},
pages = {1173--1179}
}
@article{pinol-romaShuttlingPremRNABinding1992,
title = {Shuttling of Pre-{{mRNA}} Binding Proteins between Nucleus and Cytoplasm},
author = {Piñol-Roma, S. and Dreyfuss, G.},
date = {1992-02-20},
journaltitle = {Nature},
shortjournal = {Nature},
volume = {355},
number = {6362},
eprint = {1371331},
eprinttype = {pmid},
pages = {730--732},
issn = {0028-0836},
doi = {10.1038/355730a0},
abstract = {RNA polymerase II transcripts, heterogeneous nuclear RNAs (hnRNAs), associate in the nucleus with specific proteins that bind premessenger RNA (hnRNP proteins) and with small nuclear ribonucleoprotein particles (snRNPs). These hnRNA-hnRNP-snRNP complexes assemble on nascent transcripts and hnRNA is processed to mRNA in them. HnRNP proteins have been localized to the nucleoplasm and their functions were presumed to be limited to nuclear events in mRNA biogenesis. It was proposed that an exchange of hnRNP for mRNA-binding proteins accompanies transport of mRNA from the nucleus to the cytoplasm. We show here that several of the abundant hnRNP proteins, including A1, shuttle between the nucleus and the cytoplasm. HnRNP proteins may thus also have cytoplasmic functions. Furthermore, when in the cytoplasm, A1 is bound to mRNA and RNA polymerase II transcription is necessary before it can return to the nucleus. We propose that the cytoplasmic ribonucleoprotein complex of mRNA with hnRNP proteins is the substrate of nuclear-cytoplasmic transport of mRNA.},
langid = {english},
keywords = {Animals,Cell Nucleus,Cytoplasm,Dactinomycin,DNA Polymerase II,Fluorescent Antibody Technique,HeLa Cells,Heterogeneous Nuclear Ribonucleoprotein A1,Heterogeneous-Nuclear Ribonucleoprotein Group A-B,Heterogeneous-Nuclear Ribonucleoproteins,Humanities and Social Sciences,Humans,multidisciplinary,Poly A,Ribonucleoproteins,RNA,RNA Messenger,RNA Splicing,Science,Ultraviolet Rays,Xenopus laevis}
}
@article{plinerCiceroPredictsCisRegulatory2018,
title = {Cicero {{Predicts}} Cis-{{Regulatory DNA Interactions}} from {{Single-Cell Chromatin Accessibility Data}}},
author = {Pliner, Hannah A. and Packer, Jonathan S. and McFaline-Figueroa, José L. and Cusanovich, Darren A. and Daza, Riza M. and Aghamirzaie, Delasa and Srivatsan, Sanjay and Qiu, Xiaojie and Jackson, Dana and Minkina, Anna and Adey, Andrew C. and Steemers, Frank J. and Shendure, Jay and Trapnell, Cole},
date = {2018-09-06},
journaltitle = {Molecular Cell},
shortjournal = {Mol Cell},
volume = {71},
number = {5},
eprint = {30078726},
eprinttype = {pmid},
pages = {858-871.e8},
issn = {1097-4164},
doi = {10.1016/j.molcel.2018.06.044},
abstract = {Linking regulatory DNA elements to their target genes, which may be located hundreds of kilobases away, remains challenging. Here, we introduce Cicero, an algorithm that identifies co-accessible pairs of DNA elements using single-cell chromatin accessibility data and so connects regulatory elements to their putative target genes. We apply Cicero to investigate how dynamically accessible elements orchestrate gene regulation in differentiating myoblasts. Groups of Cicero-linked regulatory elements meet criteria of "chromatin hubs"-they are enriched for physical proximity, interact with a common set of transcription factors, and undergo coordinated changes in histone marks that are predictive of changes in gene expression. Pseudotemporal analysis revealed that most DNA elements remain in chromatin hubs throughout differentiation. A subset of elements bound by MYOD1 in myoblasts exhibit early opening in a PBX1- and MEIS1-dependent manner. Our strategy can be applied to dissect the architecture, sequence determinants, and mechanisms of cis-regulation on a genome-wide scale.},
langid = {english},
pmcid = {PMC6582963},
keywords = {Adolescent,ATAC-seq,Cell Differentiation,Chromatin,chromatin accessibility,Chromatin Assembly and Disassembly,co-accessibility,DNA,Enhancer Elements Genetic,Female,Gene Expression Regulation,gene regulation,Genes Homeobox,Histones,Humans,machine learning,myoblast differentiation,Myoblasts,single-cell,Transcription Factors}
}
@article{podolskyEvaluationMachineLearning2016,
title = {Evaluation of {{Machine Learning Algorithm Utilization}} for {{Lung Cancer Classification Based}} on {{Gene Expression Levels}}},
author = {Podolsky, Maxim D. and Barchuk, Anton A. and Kuznetcov, Vladimir I. and Gusarova, Natalia F. and Gaidukov, Vadim S. and Tarakanov, Segrey A.},
date = {2016},
journaltitle = {Asian Pacific journal of cancer prevention: APJCP},
shortjournal = {Asian Pac. J. Cancer Prev.},
volume = {17},
number = {2},
eprint = {26925688},
eprinttype = {pmid},
pages = {835--838},
issn = {2476-762X},
doi = {10.7314/apjcp.2016.17.2.835},
abstract = {BACKGROUND: Lung cancer remains one of the most common cancers in the world, both in terms of new cases (about 13\% of total per year) and deaths (nearly one cancer death in five), because of the high case fatality. Errors in lung cancer type or malignant growth determination lead to degraded treatment efficacy, because anticancer strategy depends on tumor morphology. MATERIALS AND METHODS: We have made an attempt to evaluate effectiveness of machine learning algorithms in the task of lung cancer classification based on gene expression levels. We processed four publicly available data sets. The Dana-Farber Cancer Institute data set contains 203 samples and the task was to classify four cancer types and sound tissue samples. With the University of Michigan data set of 96 samples, the task was to execute a binary classification of adenocarcinoma and non-neoplastic tissues. The University of Toronto data set contains 39 samples and the task was to detect recurrence, while with the Brigham and Women's Hospital data set of 181 samples it was to make a binary classification of malignant pleural mesothelioma and adenocarcinoma. We used the k-nearest neighbor algorithm (k=1, k=5, k=10), naive Bayes classifier with assumption of both a normal distribution of attributes and a distribution through histograms, support vector machine and C4.5 decision tree. Effectiveness of machine learning algorithms was evaluated with the Matthews correlation coefficient. RESULTS: The support vector machine method showed best results among data sets from the Dana-Farber Cancer Institute and Brigham and Women's Hospital. All algorithms with the exception of the C4.5 decision tree showed maximum potential effectiveness in the University of Michigan data set. However, the C4.5 decision tree showed best results for the University of Toronto data set. CONCLUSIONS: Machine learning algorithms can be used for lung cancer morphology classification and similar tasks based on gene expression level evaluation.},
langid = {english}
}
@article{ponMEF2BMutationsNonHodgkin2015,
title = {{{MEF2B}} Mutations in Non-{{Hodgkin}} Lymphoma Dysregulate Cell Migration by Decreasing {{MEF2B}} Target Gene Activation},
author = {Pon, Julia R. and Wong, Jackson and Saberi, Saeed and Alder, Olivia and Moksa, Michelle and Grace Cheng, S.-W. and Morin, Gregg B. and Hoodless, Pamela A. and Hirst, Martin and Marra, Marco A.},
date = {2015-08-06},
journaltitle = {Nature Communications},
volume = {6},
number = {1},
pages = {1--15},
issn = {2041-1723},
doi = {10.1038/ncomms8953},
url = {https://www.nature.com/articles/ncomms8953},
urldate = {2019-12-21},
abstract = {Mutations in the transcription factor MEF2B are found in diffuse large B-cell lymphoma. In this study, the authors map the DNA-binding sites of the transcription factor in cells in vitroand find that the mutations decrease the ability of MEF2B to activate transcription.},
langid = {english}
}
@article{pontMRNADecayFactor2012,
title = {{{mRNA Decay Factor AUF1 Maintains Normal Aging}}, {{Telomere Maintenance}}, and {{Suppression}} of {{Senescence}} by {{Activation}} of {{Telomerase Transcription}}},
author = {Pont, Adam R. and Sadri, Navid and Hsiao, Susan J. and Smith, Susan and Schneider, Robert J.},
date = {2012-07-13},
journaltitle = {Molecular Cell},
shortjournal = {Molecular Cell},
volume = {47},
number = {1},
eprint = {22633954},
eprinttype = {pmid},
pages = {5--15},
publisher = {Elsevier},
issn = {1097-2765},
doi = {10.1016/j.molcel.2012.04.019},
url = {https://www.cell.com/molecular-cell/abstract/S1097-2765(12)00341-3},
urldate = {2022-09-27},
langid = {english}
}
@article{prietoRNARegulatorsLeukemia2020,
title = {{{RNA Regulators}} in {{Leukemia}} and {{Lymphoma}}},
author = {Prieto, Camila and Kharas, Michael G.},
date = {2020-05},
journaltitle = {Cold Spring Harbor Perspectives in Medicine},
shortjournal = {Cold Spring Harb Perspect Med},
volume = {10},
number = {5},
eprint = {31615866},
eprinttype = {pmid},
pages = {a034967},
issn = {2157-1422},
doi = {10.1101/cshperspect.a034967},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7197419/},
urldate = {2022-09-25},
abstract = {Posttranscriptional regulation of mRNA is a powerful and tightly controlled process in which cells command the integrity, diversity, and abundance of their protein products. RNA-binding proteins (RBPs) are the principal players that control many intermediary steps of posttranscriptional regulation. Recent advances in this field have discovered the importance of RBPs in hematological diseases. Herein we will review a number of RBPs that have been determined to play critical functions in leukemia and lymphoma. Furthermore, we will discuss the potential therapeutic strategies that are currently being studied to specifically target RBPs in these diseases.},
pmcid = {PMC7197419}
}
@article{quesadaExomeSequencingIdentifies2011,
title = {Exome Sequencing Identifies Recurrent Mutations of the Splicing Factor {{SF3B1}} Gene in Chronic Lymphocytic Leukemia},
author = {Quesada, Víctor and Conde, Laura and Villamor, Neus and Ordóñez, Gonzalo R. and Jares, Pedro and Bassaganyas, Laia and Ramsay, Andrew J. and Beà, Sílvia and Pinyol, Magda and Martínez-Trillos, Alejandra and López-Guerra, Mónica and Colomer, Dolors and Navarro, Alba and Baumann, Tycho and Aymerich, Marta and Rozman, María and Delgado, Julio and Giné, Eva and Hernández, Jesús M. and González-Díaz, Marcos and Puente, Diana A. and Velasco, Gloria and Freije, José M. P. and Tubío, José M. C. and Royo, Romina and Gelpí, Josep L. and Orozco, Modesto and Pisano, David G. and Zamora, Jorge and Vázquez, Miguel and Valencia, Alfonso and Himmelbauer, Heinz and Bayés, Mónica and Heath, Simon and Gut, Marta and Gut, Ivo and Estivill, Xavier and López-Guillermo, Armando and Puente, Xose S. and Campo, Elías and López-Otín, Carlos},
date = {2011-12-11},
journaltitle = {Nature Genetics},
shortjournal = {Nat. Genet.},
volume = {44},
number = {1},
eprint = {22158541},
eprinttype = {pmid},
pages = {47--52},
issn = {1546-1718},
doi = {10.1038/ng.1032},
abstract = {Here we perform whole-exome sequencing of samples from 105 individuals with chronic lymphocytic leukemia (CLL), the most frequent leukemia in adults in Western countries. We found 1,246 somatic mutations potentially affecting gene function and identified 78 genes with predicted functional alterations in more than one tumor sample. Among these genes, SF3B1, encoding a subunit of the spliceosomal U2 small nuclear ribonucleoprotein (snRNP), is somatically mutated in 9.7\% of affected individuals. Further analysis in 279 individuals with CLL showed that SF3B1 mutations were associated with faster disease progression and poor overall survival. This work provides the first comprehensive catalog of somatic mutations in CLL with relevant clinical correlates and defines a large set of new genes that may drive the development of this common form of leukemia. The results reinforce the idea that targeting several well-known genetic pathways, including mRNA splicing, could be useful in the treatment of CLL and other malignancies.},
langid = {english},
keywords = {Amino Acid Sequence,Disease Progression,Exome,Humans,Leukemia Lymphocytic Chronic B-Cell,Mutation,Phosphoproteins,Ribonucleoprotein U2 Small Nuclear,RNA Splicing Factors,Sequence Alignment}
}
@article{rahbariUnderstandingGenomicStructure2017,
title = {Understanding the {{Genomic Structure}} of {{Copy}}‐{{Number Variation}} of the {{Low}}‐{{Affinity Fcγ Receptor Region Allows Confirmation}} of the {{Association}} of {{FCGR3B Deletion}} with {{Rheumatoid Arthritis}}},
author = {Rahbari, Raheleh and Zuccherato, Luciana W and Tischler, German and Chihota, Belinda and Ozturk, Hasret and Saleem, Sara and Tarazona‐Santos, Eduardo and Machado, Lee R and Hollox, Edward J},
date = {2017},
journaltitle = {Human Mutation},
volume = {38},
number = {4},
eprint = {27995740},
eprinttype = {pmid},
pages = {390--399},
issn = {1098-1004},
doi = {10.1002/humu.23159},
url = {http://dx.doi.org/10.1002/humu.23159},
abstract = {Fcγ receptors are a family of cell–surface receptors that are expressed by a host of different innate and adaptive immune cells, and mediate inflammatory responses by binding the Fc portion of immunoglobulin G. In humans, five low-affinity receptors are encoded by the genes FCGR2A, FCGR2B, FCGR2C, FCGR3A, and FCGR3B, which are located in an 82.5-kb segmental tandem duplication on chromosome 1q23.3, which shows extensive copy-number variation (CNV). Deletions of FCGR3B have been suggested to increase the risk of inflammatory diseases such as systemic lupus erythematosus and rheumatoid arthritis (RA). In this study, we identify the deletion breakpoints of FCGR3B deletion alleles in the UK population and endogamous native American population, and show that some but not all alleles are likely to be identical-by-descent. We also localize a duplication breakpoint, confirming that the mechanism of CNV generation is nonallelic homologous recombination, and identify several alleles with gene conversion events using fosmid sequencing data. We use information on the structure of the deletion alleles to distinguish FCGR3B deletions from FCGR3A deletions in whole-genome array comparative genomic hybridization (aCGH) data. Reanalysis of published aCGH data using this approach supports association of FCGR3B deletion with increased risk of RA in a large cohort of 1,982 cases and 3,271 controls (odds ratio 1.61, P = 2.9×10−3).}
}
@article{raiCoordinatedExpressionMicroRNA1552008,
title = {Coordinated Expression of {{microRNA-155}} and Predicted Target Genes in Diffuse Large {{B-cell}} Lymphoma.},
author = {Rai, Deepak and Karanti, Shailaja and Jung, Inkyung and Dahia, Patricia L M and Aguiar, Ricardo C T},
date = {2008-02},
journaltitle = {Cancer genetics and cytogenetics},
volume = {181},
number = {1},
pages = {8--15}
}
@article{ramanathanMRNACappingBiological2016,
title = {{{mRNA}} Capping: Biological Functions and Applications},
shorttitle = {{{mRNA}} Capping},
author = {Ramanathan, Anand and Robb, G. Brett and Chan, Siu-Hong},
date = {2016-09-19},
journaltitle = {Nucleic Acids Research},
shortjournal = {Nucleic Acids Res},
volume = {44},
number = {16},
eprint = {27317694},
eprinttype = {pmid},
pages = {7511--7526},
issn = {1362-4962},
doi = {10.1093/nar/gkw551},
abstract = {The 5' m7G cap is an evolutionarily conserved modification of eukaryotic mRNA. Decades of research have established that the m7G cap serves as a unique molecular module that recruits cellular proteins and mediates cap-related biological functions such as pre-mRNA processing, nuclear export and cap-dependent protein synthesis. Only recently has the role of the cap 2'O methylation as an identifier of self RNA in the innate immune system against foreign RNA has become clear. The discovery of the cytoplasmic capping machinery suggests a novel level of control network. These new findings underscore the importance of a proper cap structure in the synthesis of functional messenger RNA. In this review, we will summarize the current knowledge of the biological roles of mRNA caps in eukaryotic cells. We will also discuss different means that viruses and their host cells use to cap their RNA and the application of these capping machineries to synthesize functional mRNA. Novel applications of RNA capping enzymes in the discovery of new RNA species and sequencing the microbiome transcriptome will also be discussed. We will end with a summary of novel findings in RNA capping and the questions these findings pose.},
langid = {english},
pmcid = {PMC5027499},
keywords = {Animals,Eukaryotic Cells,Humans,Models Molecular,Nucleotidyltransferases,RNA Caps,RNA Viral}
}
@article{rauchHeterogeneousNuclearRibonucleoprotein2010,
title = {Heterogeneous Nuclear Ribonucleoprotein {{H}} Blocks {{MST2-mediated}} Apoptosis in Cancer Cells by Regulating {{A-Raf}} Transcription},
author = {Rauch, Jens and O'Neill, Eric and Mack, Brigitte and Matthias, Christoph and Munz, Markus and Kolch, Walter and Gires, Olivier},
date = {2010-02-15},
journaltitle = {Cancer Research},
shortjournal = {Cancer Res.},
volume = {70},
number = {4},
eprint = {20145135},
eprinttype = {pmid},
pages = {1679--1688},
issn = {1538-7445},
doi = {10.1158/0008-5472.CAN-09-2740},
abstract = {A-Raf belongs to the family of oncogenic Raf kinases that are involved in mitogenic signaling by activating the mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK) kinase (MEK)-ERK pathway. Low kinase activity of A-Raf toward MEK suggested that A-Raf might have alternative functions. Here, we show that A-Raf prevents cancer cell apoptosis contingent on the expression of the heterogeneous nuclear ribonucleoprotein H (hnRNP H) splice factor, which is required for the correct transcription and expression of a-raf. Apoptosis was prevented by A-Raf through sequestration and inactivation of the proapoptotic MST2 kinase. Small interfering RNA-mediated knockdown of hnRNP H or A-Raf resulted in MST2-dependent apoptosis. In contrast, enforced expression of either hnRNP H or A-Raf partially counteracted apoptosis induced by etoposide. In vivo expression studies of colon specimens corroborated the overexpression of hnRNP H in malignant tissues and its correlation with A-Raf levels. Our findings define a novel mechanism that is usurped in tumor cells to escape naturally imposed apoptotic signals.},
langid = {english},
pmcid = {PMC2880479},
keywords = {Apoptosis,Cells Cultured,Gene Expression Regulation Neoplastic,HCT116 Cells,HeLa Cells,Heterogeneous-Nuclear Ribonucleoprotein Group F-H,Humans,Models Biological,Neoplasms,Protein Binding,Protein-Serine-Threonine Kinases,Proto-Oncogene Proteins A-raf,RNA Small Interfering,Signal Transduction,Transcription Genetic}
}
@article{rauchInterferonRegulatoryFactor2020,
title = {Interferon Regulatory Factor 4 as a Therapeutic Target in Adult {{T-cell}} Leukemia Lymphoma},
author = {Rauch, Daniel A. and Olson, Sydney L. and Harding, John C. and Sundaramoorthi, Hemalatha and Kim, Youngsoo and Zhou, Tianyuan and MacLeod, A. Robert and Challen, Grant and Ratner, Lee},
date = {2020-08-28},
journaltitle = {Retrovirology},
shortjournal = {Retrovirology},
volume = {17},
eprint = {32859220},
eprinttype = {pmid},
pages = {27},
issn = {1742-4690},
doi = {10.1186/s12977-020-00535-z},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456374/},
urldate = {2021-11-30},
abstract = {Background Adult T-cell leukemia lymphoma (ATLL) is a chemotherapy-resistant malignancy with a median survival of less than one year that will afflict between one hundred thousand and one million individuals worldwide who are currently infected with human T-cell leukemia virus type 1. Recurrent somatic mutations in host genes have exposed the T-cell receptor pathway through nuclear factor κB to interferon regulatory factor 4 (IRF4) as an essential driver for this malignancy. We sought to determine if IRF4 represents a therapeutic target for ATLL and to identify downstream effectors and biomarkers of IRF4 signaling in vivo. Results ATLL cell lines, particularly Tax viral oncoprotein-negative cell lines, that most closely resemble ATLL in humans, were sensitive to dose- and time-dependent inhibition by a next-generation class of IRF4 antisense oligonucleotides (ASOs) that employ constrained ethyl residues that mediate RNase H-dependent RNA degradation. ATLL cell lines were also sensitive to lenalidomide, which repressed IRF4 expression. Both ASOs and lenalidomide inhibited ATLL proliferation in vitro and in vivo. To identify biomarkers of IRF4-mediated CD4\,+\,T-cell expansion in vivo, transcriptomic analysis identified several genes that encode key regulators of ATLL, including interleukin 2 receptor subunits α and β, KIT ligand, cytotoxic T-lymphocyte-associated protein 4, and thymocyte selection-associated high mobility group protein TOX 2. Conclusions These data support the pursuit of IRF4 as a therapeutic target in ATLL with the use of either ASOs or lenalidomide.},
pmcid = {PMC7456374}
}
@online{Rbfox1LymphomaGoogle,
title = {Rbfox1 Lymphoma - {{Google Search}}},
url = {https://www.google.com/search?q=rbfox1+lymphoma&rlz=1C5CHFA_enCA1020CA1020&oq=rbfox1+lymphoma&aqs=chrome..69i57j33i160l2.2521j0j4&sourceid=chrome&ie=UTF-8},
urldate = {2022-10-27}
}
@article{reddyGeneticFunctionalDrivers2017,
title = {Genetic and {{Functional Drivers}} of {{Diffuse Large B Cell Lymphoma}}.},
author = {Reddy, Anupama and Zhang, Jenny and Davis, Nicholas S and Moffitt, Andrea B and Love, Cassandra L and Waldrop, Alexander and Leppa, Sirpa and Pasanen, Annika and Meriranta, Leo and Karjalainen-Lindsberg, Marja-Liisa and Nørgaard, Peter and Pedersen, Mette and Gang, Anne O and Høgdall, Estrid and Heavican, Tayla B and Lone, Waseem and Iqbal, Javeed and Qin, Qiu and Li, Guojie and Kim, So Young and Healy, Jane and Richards, Kristy L and Fedoriw, Yuri and Bernal-Mizrachi, Leon and Koff, Jean L and Staton, Ashley D and Flowers, Christopher R and Paltiel, Ora and Goldschmidt, Neta and Calaminici, Maria and Clear, Andrew and Gribben, John and Nguyen, Evelyn and Czader, Magdalena B and Ondrejka, Sarah L and Collie, Angela and Hsi, Eric D and Tse, Eric and Au-Yeung, Rex K H and Kwong, Yok Lam and Srivastava, Gopesh and Choi, William W L and Evens, Andrew M and Pilichowska, Monika and Sengar, Manju and Reddy, Nishitha and Li, Shaoying and Chadburn, Amy and Gordon, Leo I and Jaffe, Elaine S and Levy, Shawn and Rempel, Rachel and Tzeng, Tiffany and Happ, Lanie E and Dave, Tushar and Rajagopalan, Deepthi and Datta, Jyotishka and Dunson, David B and Dave, Sandeep S},
date = {2017-10},
journaltitle = {Cell},
volume = {171},
number = {2},
pages = {481--494.e15},
pmcid = {PMC5659841}
}
@article{reddyInternalizationRituximabEfficiency2015,
title = {Internalization of {{Rituximab}} and the {{Efficiency}} of {{B Cell Depletion}} in {{Rheumatoid Arthritis}} and {{Systemic Lupus Erythematosus}}},
author = {Reddy, Venkat and Cambridge, Geraldine and Isenberg, David A and Glennie, Martin J and Cragg, Mark S and Leandro, Maria},
date = {2015},
journaltitle = {Arthritis \& Rheumatology},
volume = {67},
number = {8},
eprint = {25916583},
eprinttype = {pmid},
pages = {2046--2055},
issn = {2326-5205},
doi = {10.1002/art.39167},
url = {http://dx.doi.org/10.1002/art.39167},
abstract = {Rituximab, a type I anti-CD20 monoclonal antibody (mAb), induces incomplete B cell depletion in some patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), thus contributing to a poor clinical response. The mechanisms of this resistance remain elusive. The purpose of this study was to determine whether type II mAb are more efficient than type I mAb at depleting B cells from RA and SLE patients, whether internalization influences the efficiency of depletion, and whether Fcγ receptor type IIb (FcγRIIb) and the B cell receptor regulate this internalization process. We used an in vitro whole blood B cell–depletion assay to assess the efficiency of depletion, flow cytometry to study cell surface protein expression, and surface fluorescence–quenching assays to assess rituximab internalization, in samples from patients with RA and patients with SLE. Paired t-test or Mann-Whitney U test was used to compare groups, and Spearman's rank correlation test was used to assess correlation. We found that type II mAb internalized significantly less rituximab than type I mAb and depleted B cells from patients with RA and SLE at least 2-fold more efficiently than type I mAb. Internalization of rituximab was highly variable between patients, was regulated by FcγRIIb, and inversely correlated with cytotoxicity in whole blood B cell–depletion assays. The lowest levels of internalization were seen in IgD– B cells, including postswitched (IgD–CD27+) memory cells. Internalization of type I anti-CD20 mAb was also partially inhibited by anti-IgM stimulation. Variability in internalization of rituximab was observed and was correlated with impaired B cell depletion. Therefore, slower-internalizing type II mAb should be considered as alternative B cell–depleting agents for the treatment of RA and SLE.}
}
@article{reichelFlowSortingExome2015,
title = {Flow Sorting and Exome Sequencing Reveal the Oncogenome of Primary {{Hodgkin}} and {{Reed-Sternberg}} Cells},
author = {Reichel, Jonathan and Chadburn, Amy and Rubinstein, Paul G. and Giulino-Roth, Lisa and Tam, Wayne and Liu, Yifang and Gaiolla, Rafael and Eng, Kenneth and Brody, Joshua and Inghirami, Giorgio and Carlo-Stella, Carmelo and Santoro, Armando and Rahal, Daoud and Totonchy, Jennifer and Elemento, Olivier and Cesarman, Ethel and Roshal, Mikhail},
date = {2015-02-12},
journaltitle = {Blood},
shortjournal = {Blood},
volume = {125},
number = {7},
eprint = {25488972},
eprinttype = {pmid},
pages = {1061--1072},
issn = {1528-0020},
doi = {10.1182/blood-2014-11-610436},
abstract = {Classical Hodgkin lymphoma (cHL) is characterized by sparsely distributed Hodgkin and Reed-Sternberg (HRS) cells amid reactive host background, complicating the acquisition of neoplastic DNA without extensive background contamination. We overcame this limitation by using flow-sorted HRS and intratumor T cells and optimized low-input exome sequencing of 10 patient samples to reveal alterations in genes involved in antigen presentation, chromosome integrity, transcriptional regulation, and ubiquitination. β-2-microglobulin (B2M) is the most commonly altered gene in HRS cells, with 7 of 10 cases having inactivating mutations that lead to loss of major histocompatibility complex class I (MHC-I) expression. Enforced wild-type B2M expression in a cHL cell line restored MHC-I expression. In an extended cohort of 145 patients, the absence of B2M protein in the HRS cells was associated with lower stage of disease, younger age at diagnosis, and better overall and progression-free survival. B2M-deficient cases encompassed most of the nodular sclerosis subtype cases and only a minority of mixed cellularity cases, suggesting that B2M deficiency determines the tumor microenvironment and may define a major subset of cHL that has more uniform clinical and morphologic features. In addition, we report previously unknown genetic alterations that may render selected patients sensitive to specific targeted therapies.},
langid = {english},
keywords = {Adolescent,Adult,Aged,Aged 80 and over,Cell Line Tumor,Cell Separation,Child,Cohort Studies,Exome,Female,Flow Cytometry,Genes Neoplasm,Genome Human,High-Throughput Nucleotide Sequencing,Hodgkin Disease,Humans,Male,Middle Aged,Reed-Sternberg Cells,Young Adult}
}
@article{rheinbayRecurrentFunctionalRegulatory2017,
title = {Recurrent and Functional Regulatory Mutations in Breast Cancer},
author = {Rheinbay, Esther and Parasuraman, Prasanna and Grimsby, Jonna and Tiao, Grace and Engreitz, Jesse M and Kim, Jaegil and Lawrence, Michael S and Taylor-Weiner, Amaro and Rodriguez-Cuevas, Sergio and Rosenberg, Mara and Hess, Julian and Stewart, Chip and Maruvka, Yosef E and Stojanov, Petar and Cortés, Maria L and Seepo, Sara and Cibulskis, Carrie and Tracy, Adam and Pugh, Trevor J and Lee, Jesse and Zheng, Zongli and Ellisen, Leif W and Iafrate, A John and Boehm, Jesse S and Gabriel, Stacey B and Meyerson, Matthew and Golub, Todd R and Baselga, José and Hidalgo-Miranda, Alfredo and Shioda, Toshi and Bernards, Andre and Lander, Eric S and Getz, Gad},
date = {2017-07},
journaltitle = {Nature},
volume = {547},
number = {7661},
pages = {55--60}
}
@article{richterRecurrentMutationID32012,
title = {Recurrent Mutation of the {{ID3}} Gene in {{Burkitt}} Lymphoma Identified by Integrated Genome, Exome and Transcriptome Sequencing},
author = {Richter, Julia and Schlesner, Matthias and Hoffmann, Steve and Kreuz, Markus and Leich, Ellen and Burkhardt, Birgit and Rosolowski, Maciej and Ammerpohl, Ole and Wagener, Rabea and Bernhart, Stephan H. and Lenze, Dido and Szczepanowski, Monika and Paulsen, Maren and Lipinski, Simone and Russell, Robert B. and Adam-Klages, Sabine and Apic, Gordana and Claviez, Alexander and Hasenclever, Dirk and Hovestadt, Volker and Hornig, Nadine and Korbel, Jan O. and Kube, Dieter and Langenberger, David and Lawerenz, Chris and Lisfeld, Jasmin and Meyer, Katharina and Picelli, Simone and Pischimarov, Jordan and Radlwimmer, Bernhard and Rausch, Tobias and Rohde, Marius and Schilhabel, Markus and Scholtysik, René and Spang, Rainer and Trautmann, Heiko and Zenz, Thorsten and Borkhardt, Arndt and Drexler, Hans G. and Möller, Peter and MacLeod, Roderick A. F. and Pott, Christiane and Schreiber, Stefan and Trümper, Lorenz and Loeffler, Markus and Stadler, Peter F. and Lichter, Peter and Eils, Roland and Küppers, Ralf and Hummel, Michael and Klapper, Wolfram and Rosenstiel, Philip and Rosenwald, Andreas and Brors, Benedikt and Siebert, Reiner and {ICGC MMML-Seq Project}},
date = {2012-12},
journaltitle = {Nature Genetics},
shortjournal = {Nat Genet},
volume = {44},
number = {12},
eprint = {23143595},
eprinttype = {pmid},
pages = {1316--1320},
issn = {1546-1718},
doi = {10.1038/ng.2469},
abstract = {Burkitt lymphoma is a mature aggressive B-cell lymphoma derived from germinal center B cells. Its cytogenetic hallmark is the Burkitt translocation t(8;14)(q24;q32) and its variants, which juxtapose the MYC oncogene with one of the three immunoglobulin loci. Consequently, MYC is deregulated, resulting in massive perturbation of gene expression. Nevertheless, MYC deregulation alone seems not to be sufficient to drive Burkitt lymphomagenesis. By whole-genome, whole-exome and transcriptome sequencing of four prototypical Burkitt lymphomas with immunoglobulin gene (IG)-MYC translocation, we identified seven recurrently mutated genes. One of these genes, ID3, mapped to a region of focal homozygous loss in Burkitt lymphoma. In an extended cohort, 36 of 53 molecularly defined Burkitt lymphomas (68\%) carried potentially damaging mutations of ID3. These were strongly enriched at somatic hypermutation motifs. Only 6 of 47 other B-cell lymphomas with the IG-MYC translocation (13\%) carried ID3 mutations. These findings suggest that cooperation between ID3 inactivation and IG-MYC translocation is a hallmark of Burkitt lymphomagenesis.},
langid = {english},
keywords = {Base Sequence,Burkitt Lymphoma,Chromosome Mapping,Chromosomes Human Pair 14,Chromosomes Human Pair 8,Cohort Studies,Female,Genes Immunoglobulin,Genes myc,Genome Human,Humans,Inhibitor of Differentiation Proteins,Male,Molecular Sequence Data,Mutation,Neoplasm Proteins,Sequence Analysis DNA,Somatic Hypermutation Immunoglobulin,Transcriptome,Translocation Genetic}
}
@article{rimszaAccurateClassificationDiffuse2011,
title = {Accurate Classification of Diffuse Large {{B-cell}} Lymphoma into Germinal Center and Activated {{B-cell}} Subtypes Using a Nuclease Protection Assay on Formalin-Fixed, Paraffin-Embedded Tissues},
author = {Rimsza, Lisa M. and Wright, George and Schwartz, Mark and Chan, Wing C. and Jaffe, Elaine S. and Gascoyne, Randy D. and Campo, Elias and Rosenwald, Andreas and Ott, German and Cook, James R. and Tubbs, Raymond R. and Braziel, Rita M. and Delabie, Jan and Miller, Tom P. and Staudt, Louis M.},
date = {2011-06-01},
journaltitle = {Clinical Cancer Research: An Official Journal of the American Association for Cancer Research},
shortjournal = {Clin Cancer Res},
volume = {17},
number = {11},
eprint = {21364035},
eprinttype = {pmid},
pages = {3727--3732},
issn = {1557-3265},
doi = {10.1158/1078-0432.CCR-10-2573},
abstract = {Classification of diffuse large B-cell lymphoma (DLBCL) into cell-of-origin (COO) subtypes based on gene expression profiles has well-established prognostic value. These subtypes, termed germinal center B cell (GCB) and activated B cell (ABC) also have different genetic alterations and overexpression of different pathways that may serve as therapeutic targets. Thus, accurate classification is essential for analysis of clinical trial results and planning new trials by using targeted agents. The current standard for COO classification uses gene expression profiling (GEP) of snap frozen tissues, and a Bayesian predictor algorithm. However, this is generally not feasible. In this study, we investigated whether the qNPA technique could be used for accurate classification of COO by using formalin-fixed, paraffin-embedded (FFPE) tissues. We analyzed expression levels of 14 genes in 121 cases of R-CHOP-treated DLBCL that had previously undergone GEP by using the Affymetrix U133 Plus 2.0 microarray and had matching FFPE blocks. Results were evaluated by using the previously published algorithm with a leave-one-out cross-validation approach. These results were compared with COO classification based on frozen tissue GEP profiles. For each case, a probability statistic was generated indicating the likelihood that the classification by using qNPA was accurate. When data were dichotomized into GCB or non-GCB, overall accuracy was 92\%. The qNPA technique accurately categorized DLBCL into GCB and ABC subtypes, as defined by GEP. This approach is quantifiable, applicable to FFPE tissues with no technical failures, and has potential for significant impact on DLBCL research and clinical trial development.},
langid = {english},
pmcid = {PMC3107869},
keywords = {B-Lymphocyte Subsets,Gene Expression Profiling,Gene Expression Regulation Neoplastic,Germinal Center,Humans,Lymphocyte Activation,Lymphoma Large B-Cell Diffuse,Nuclease Protection Assays,Oligonucleotide Array Sequence Analysis,Paraffin Embedding,Prognosis}
}
@article{rimszaClassificationDiffuseLarge,
title = {Classification of {{Diffuse Large B}} Cell {{Lymphoma}} into {{Germinal Center}} and {{Activated B}} Cell {{Subtypes Using}} a {{Nuclease Protection Assay}} on {{Paraffin Embedded Tissues}}.},
author = {Rimsza, Lisa M and Wright, George W and Schwartz, Mark and Chan, Wing and Jaffe, Elaine and Gascoyne, Randy D and Campo, Elias and Rosenwald, Andreas and Ott, German and Cook, James and Tubbs, Raymond R and Braziel, Rita M and Delabie, Jan and Miller, Thomas P and Staudt, Louis M},
journaltitle = {Clin Cancer Res}
}
@article{rimszaLossMHCClass2004,
title = {Loss of {{MHC}} Class {{II}} Gene and Protein Expression in Diffuse Large {{B-cell}} Lymphoma Is Related to Decreased Tumor Immunosurveillance and Poor Patient Survival Regardless of Other Prognostic Factors: A Follow-up Study from the {{Leukemia}} and {{Lymphoma Molecular Profiling Project}}},
author = {Rimsza, L M},
date = {2004-06},
journaltitle = {Blood},
volume = {103},
number = {11},
pages = {4251--4258}
}
@article{ritchieLimmaPowersDifferential2015,
title = {Limma Powers Differential Expression Analyses for {{RNA-sequencing}} and Microarray Studies},
author = {Ritchie, Matthew E. and Phipson, Belinda and Wu, Di and Hu, Yifang and Law, Charity W. and Shi, Wei and Smyth, Gordon K.},
date = {2015-04-20},
journaltitle = {Nucleic Acids Research},
shortjournal = {Nucleic Acids Research},
volume = {43},
number = {7},
pages = {e47},
issn = {0305-1048},
doi = {10.1093/nar/gkv007},
url = {https://doi.org/10.1093/nar/gkv007},
urldate = {2024-03-19},
abstract = {limma is an R/Bioconductor software package that provides an integrated solution for analysing data from gene expression experiments. It contains rich features for handling complex experimental designs and for information borrowing to overcome the problem of small sample sizes. Over the past decade, limma has been a popular choice for gene discovery through differential expression analyses of microarray and high-throughput PCR data. The package contains particularly strong facilities for reading, normalizing and exploring such data. Recently, the capabilities of limma have been significantly expanded in two important directions. First, the package can now perform both differential expression and differential splicing analyses of RNA sequencing (RNA-seq) data. All the downstream analysis tools previously restricted to microarray data are now available for RNA-seq as well. These capabilities allow users to analyse both RNA-seq and microarray data with very similar pipelines. Second, the package is now able to go past the traditional gene-wise expression analyses in a variety of ways, analysing expression profiles in terms of co-regulated sets of genes or in terms of higher-order expression signatures. This provides enhanced possibilities for biological interpretation of gene expression differences. This article reviews the philosophy and design of the limma package, summarizing both new and historical features, with an emphasis on recent enhancements and features that have not been previously described.}
}
@article{ritzRecurrentMutationsSTAT62009,
title = {Recurrent Mutations of the {{STAT6 DNA}} Binding Domain in Primary Mediastinal {{B-cell}} Lymphoma},
author = {Ritz, Olga and Guiter, Chrystelle and Castellano, Flavia and Dorsch, Karola and Melzner, Julia and Jais, Jean-Philippe and Dubois, Gwendoline and Gaulard, Philippe and Möller, Peter and Leroy, Karen},
date = {2009-08-06},
journaltitle = {Blood},
shortjournal = {Blood},
volume = {114},
number = {6},
eprint = {19423726},
eprinttype = {pmid},
pages = {1236--1242},
issn = {1528-0020},
doi = {10.1182/blood-2009-03-209759},
abstract = {Primary mediastinal B-cell lymphoma (PMBL) is a separate entity of aggressive B-cell lymphoma, characterized by a constitutive activation of janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway, also observed in Hodgkin lymphoma. Although many cancers exhibit constitutive JAK-STAT pathway activation, mutations of STAT genes have not been reported in neoplasms. Here, we show that MedB-1 PMBL-derived and L1236 Hodgkin-derived cell lines and 20 of 55 (36\%) PMBL cases harbor heterozygous missense mutations in STAT6 DNA binding domain, whereas no mutation was found in 25 diffuse large B-cell lymphoma samples. In 3 cases, somatic origin was indicated by the absence of the mutations in the nontumoral tissue. The pattern of STAT6 mutations was different from the classical features of somatic hypermutations. The mutant STAT6 proteins showed a decreased DNA binding ability in transfected HEK cells, but no decrease in expression of STAT6 canonical target genes was observed in PMBL cases with a mutated STAT6 gene. Although the oncogenic properties of STAT6 mutant proteins remain to be determined, their recurrent selection in PMBL strongly argues for their involvement in the pathogenesis of this aggressive B-cell lymphoma.},
langid = {english},
pmcid = {PMC2824656},
keywords = {Cell Line Tumor,Female,Gene Expression Regulation Neoplastic,Humans,Lymphoma Large B-Cell Diffuse,Male,Mediastinal Neoplasms,Mutation,Neoplasm Proteins,Protein Structure Tertiary,Signal Transduction,STAT6 Transcription Factor}
}
@article{robertsGeneticAlterationsActivating2012,
title = {Genetic Alterations Activating Kinase and Cytokine Receptor Signaling in High-Risk Acute Lymphoblastic Leukemia},
author = {Roberts, Kathryn G. and Morin, Ryan D. and Zhang, Jinghui and Hirst, Martin and Zhao, Yongjun and Su, Xiaoping and Chen, Shann-Ching and Payne-Turner, Debbie and Churchman, Michelle and Harvey, Richard C. and Chen, Xiang and Kasap, Corynn and Yan, Chunhua and Becksfort, Jared and Finney, Richard P. and Teachey, David T. and Maude, Shannon L. and Tse, Kane and Moore, Richard and Jones, Steven and Mungall, Karen and Birol, Inanc and Edmonson, Michael N. and Hu, Ying and Buetow, Kenneth E. and Chen, I-Ming and Carroll, William L. and Wei, Lei and Ma, Jing and Kleppe, Maria and Levine, Ross L. and Garcia-Manero, Guillermo and Larsen, Eric and Shah, Neil P. and Devidas, Meenakshi and Reaman, Gregory and Smith, Malcolm and Paugh, Steven W. and Evans, William E. and Grupp, Stephan A. and Jeha, Sima and Pui, Ching-Hon and Gerhard, Daniela S. and Downing, James R. and Willman, Cheryl L. and Loh, Mignon and Hunger, Stephen P. and Marra, Marco and Mullighan, Charles G.},
date = {2012-08-14},
journaltitle = {Cancer cell},
shortjournal = {Cancer Cell},
volume = {22},
number = {2},
eprint = {22897847},
eprinttype = {pmid},
pages = {153--166},
issn = {1535-6108},
doi = {10.1016/j.ccr.2012.06.005},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3422513/},
urldate = {2020-07-16},
abstract = {Genomic profiling has identified a subtype of high-risk B-progenitor acute lymphoblastic leukemia (B-ALL) with alteration of IKZF1, a gene expression profile similar to BCR-ABL1-positive ALL and poor outcome (Ph-like ALL). The genetic alterations that activate kinase signaling in Ph-like ALL are poorly understood. We performed transcriptome and whole genome sequencing on 15 cases of Ph-like ALL, and identified rearrangements involving ABL1, JAK2, PDGFRB, CRLF2 and EPOR, activating mutations of IL7R and FLT3, and deletion of SH2B3, which encodes the JAK2 negative regulator LNK. Importantly, several of these alterations induce transformation that is attenuated with tyrosine kinase inhibitors, suggesting the treatment outcome of these patients may be improved with targeted therapy.},
pmcid = {PMC3422513}
}
@article{rocoClassSwitchRecombinationOccurs2019,
title = {Class-{{Switch Recombination Occurs Infrequently}} in {{Germinal Centers}}},
author = {Roco, Jonathan A. and Mesin, Luka and Binder, Sebastian C. and Nefzger, Christian and Gonzalez-Figueroa, Paula and Canete, Pablo F. and Ellyard, Julia and Shen, Qian and Robert, Philippe A. and Cappello, Jean and Vohra, Harpreet and Zhang, Yang and Nowosad, Carla R. and Schiepers, Arien and Corcoran, Lynn M. and Toellner, Kai-Michael and Polo, Jose M. and Meyer-Hermann, Michael and Victora, Gabriel D. and Vinuesa, Carola G.},
date = {2019-08-20},
journaltitle = {Immunity},
shortjournal = {Immunity},
volume = {51},
number = {2},
eprint = {31375460},
eprinttype = {pmid},
pages = {337-350.e7},
publisher = {Elsevier},
issn = {1074-7613},
doi = {10.1016/j.immuni.2019.07.001},
url = {https://www.cell.com/immunity/abstract/S1074-7613(19)30317-6},
urldate = {2020-05-25},
langid = {english}
}
@article{roghanianAntagonisticHumanFcgRIIB2015,
title = {Antagonistic {{Human FcγRIIB}} ({{CD32B}}) {{Antibodies Have Anti-Tumor Activity}} and {{Overcome Resistance}} to {{Antibody Therapy In Vivo}}},
author = {Roghanian, Ali and Teige, Ingrid and Mårtensson, Linda and Cox, Kerry L. and Kovacek, Mathilda and Ljungars, Anne and Mattson, Jenny and Sundberg, Annika and Vaughan, Andrew T. and Shah, Vallari and Smyth, Neil R. and Sheth, Bhavwanti and Chan, H.T. Claude and Li, Zhan-Chun and Williams, Emily L. and Manfredi, Giusi and Oldham, Robert J. and Mockridge, C. Ian and James, Sonya A. and Dahal, Lekh N. and Hussain, Khiyam and Nilsson, Björn and Verbeek, J. Sjef and Juliusson, Gunnar and Hansson, Markus and Jerkeman, Mats and Johnson, Peter W.M. and Davies, Andrew and Beers, Stephen A. and Glennie, Martin J. and Frendéus, Björn and Cragg, Mark S.},
date = {2015},
journaltitle = {Cancer Cell},
volume = {27},
number = {4},
eprint = {25873171},
eprinttype = {pmid},
pages = {473--488},
issn = {1535-6108},
doi = {10.1016/j.ccell.2015.03.005},
url = {http://dx.doi.org/10.1016/j.ccell.2015.03.005},
abstract = {Therapeutic antibodies have transformed cancer therapy, unlocking mechanisms of action by engaging the immune system. Unfortunately, cures rarely occur and patients display intrinsic or acquired resistance. Here, we demonstrate the therapeutic potential of targeting human (h) FcγRIIB (CD32B), a receptor implicated in immune cell desensitization and tumor cell resistance. FcγRIIB-blocking antibodies prevented internalization of the CD20-specific antibody rituximab, thereby maximizing cell surface accessibility and immune effector cell mediated antitumor activity. In hFcγRIIB-transgenic (Tg) mice, FcγRIIB-blocking antibodies effectively deleted target cells in combination with rituximab, and other therapeutic antibodies, from resistance-prone stromal compartments. Similar efficacy was seen in primary human tumor xenografts, including with cells from patients with relapsed/refractory disease. These data support the further development of hFcγRIIB antibodies for clinical assessment.}
}
@article{roghanianResistanceFutileTargeting2016,
title = {Resistance Is Futile: {{Targeting}} the Inhibitory {{FcγRIIB}} ({{CD32B}}) to Maximize Immunotherapy.},
author = {Roghanian, Ali and Cragg, Mark S and Frendéus, Bjorn},
date = {2016-02},
journaltitle = {OncoImmunology},
volume = {5},
number = {2},
pages = {e1069939}
}
@article{romero-camareroGerminalCentreProtein2013,
title = {Germinal Centre Protein {{HGAL}} Promotes Lymphoid Hyperplasia and Amyloidosis via {{BCR-mediated Syk}} Activation.},
author = {Romero-Camarero, Isabel and Jiang, Xiaoyu and Natkunam, Yasodha and Lu, Xiaoqing and Vicente-Dueñas, Carolina and Gonzalez-Herrero, Ines and Flores, Teresa and Garcia, Juan Luis and McNamara, George and Kunder, Christian and Zhao, Shuchun and Segura, Victor and Fontan, Lorena and Martinez-Climent, Jose A and García-Criado, Francisco Javier and Theis, Jason D and Dogan, Ahmet and Campos-Sánchez, Elena and Green, Michael R and Alizadeh, Ash A and Cobaleda, Cesar and Sánchez-García, Isidro and Lossos, Izidore S},
date = {2013},
journaltitle = {Nature communications},
volume = {4},
pages = {1338}
}
@article{roschewskiCirculatingTumourDNA,
title = {Circulating Tumour {{DNA}} and {{CT}} Monitoring in Patients with Untreated Diffuse Large {{B-cell}} Lymphoma: A Correlative Biomarker Study.},
author = {Roschewski, Mark and Dunleavy, Kieron and Pittaluga, Stefania and Moorhead, Martin and Pepin, Francois and Kong, Katherine and Shovlin, Margaret and Jaffe, Elaine S and Staudt, Louis M and Lai, Catherine and Steinberg, Seth M and Chen, Clara C and Zheng, Jianbiao and Willis, Thomas D and Faham, Malek and Wilson, Wyndham H},
journaltitle = {Lancet Oncol}
}
@article{rosenwaldGeneExpressionProfiling,
title = {Gene Expression Profiling of Diffuse Large {{B-cell}} Lymphoma},
author = {Rosenwald, A and Staudt, L},
journaltitle = {Leuk lymphoma},
volume = {44 Suppl 3},
pages = {S41--7--S41--7}
}
@article{rosenwaldMolecularDiagnosisPrimary2003,
title = {Molecular Diagnosis of Primary Mediastinal {{B}} Cell Lymphoma Identifies a Clinically Favorable Subgroup of Diffuse Large {{B}} Cell Lymphoma Related to {{Hodgkin}} Lymphoma},
author = {Rosenwald, Andreas and Wright, George and Leroy, Karen and Yu, Xin and Gaulard, Philippe and Gascoyne, Randy D. and Chan, Wing C. and Zhao, Tong and Haioun, Corinne and Greiner, Timothy C. and Weisenburger, Dennis D. and Lynch, James C. and Vose, Julie and Armitage, James O. and Smeland, Erlend B. and Kvaloy, Stein and Holte, Harald and Delabie, Jan and Campo, Elias and Montserrat, Emili and Lopez-Guillermo, Armando and Ott, German and Muller-Hermelink, H. Konrad and Connors, Joseph M. and Braziel, Rita and Grogan, Thomas M. and Fisher, Richard I. and Miller, Thomas P. and LeBlanc, Michael and Chiorazzi, Michael and Zhao, Hong and Yang, Liming and Powell, John and Wilson, Wyndham H. and Jaffe, Elaine S. and Simon, Richard and Klausner, Richard D. and Staudt, Louis M.},
date = {2003-09-15},
journaltitle = {The Journal of Experimental Medicine},
shortjournal = {J Exp Med},
volume = {198},
number = {6},
eprint = {12975453},
eprinttype = {pmid},
pages = {851--862},
issn = {0022-1007},
doi = {10.1084/jem.20031074},
abstract = {Using current diagnostic criteria, primary mediastinal B cell lymphoma (PMBL) cannot be distinguished from other types of diffuse large B cell lymphoma (DLBCL) reliably. We used gene expression profiling to develop a more precise molecular diagnosis of PMBL. PMBL patients were considerably younger than other DLBCL patients, and their lymphomas frequently involved other thoracic structures but not extrathoracic sites typical of other DLBCLs. PMBL patients had a relatively favorable clinical outcome, with a 5-yr survival rate of 64\% compared with 46\% for other DLBCL patients. Gene expression profiling strongly supported a relationship between PMBL and Hodgkin lymphoma: over one third of the genes that were more highly expressed in PMBL than in other DLBCLs were also characteristically expressed in Hodgkin lymphoma cells. PDL2, which encodes a regulator of T cell activation, was the gene that best discriminated PMBL from other DLBCLs and was also highly expressed in Hodgkin lymphoma cells. The genomic loci for PDL2 and several neighboring genes were amplified in over half of the PMBLs and in Hodgkin lymphoma cell lines. The molecular diagnosis of PMBL should significantly aid in the development of therapies tailored to this clinically and pathogenetically distinctive subgroup of DLBCL.},
langid = {english},
pmcid = {PMC2194208},
keywords = {Adult,Chromosomes Human Pair 19,Diagnosis Differential,Gene Expression Profiling,Hodgkin Disease,Humans,Lymphoma B-Cell,Lymphoma Large B-Cell Diffuse,Mediastinal Neoplasms,Middle Aged,Molecular Diagnostic Techniques,Oligonucleotide Array Sequence Analysis,Survival Rate,Treatment Outcome,Tumor Cells Cultured}
}
@article{rosenwaldProliferationGeneExpression2003,
title = {The Proliferation Gene Expression Signature Is a Quantitative Integrator of Oncogenic Events That Predicts Survival in Mantle Cell Lymphoma},
author = {Rosenwald, Andreas and Wright, George and Wiestner, Adrian and Chan, Wing C. and Connors, Joseph M. and Campo, Elias and Gascoyne, Randy D. and Grogan, Thomas M. and Muller-Hermelink, H. Konrad and Smeland, Erlend B. and Chiorazzi, Michael and Giltnane, Jena M. and Hurt, Elaine M. and Zhao, Hong and Averett, Lauren and Henrickson, Sarah and Yang, Liming and Powell, John and Wilson, Wyndham H. and Jaffe, Elaine S. and Simon, Richard and Klausner, Richard D. and Montserrat, Emilio and Bosch, Francesc and Greiner, Timothy C. and Weisenburger, Dennis D. and Sanger, Warren G. and Dave, Bhavana J. and Lynch, James C. and Vose, Julie and Armitage, James O. and Fisher, Richard I. and Miller, Thomas P. and LeBlanc, Michael and Ott, German and Kvaloy, Stein and Holte, Harald and Delabie, Jan and Staudt, Louis M.},
date = {2003-02-01},
journaltitle = {Cancer Cell},
shortjournal = {Cancer Cell},
volume = {3},
number = {2},
eprint = {12620412},
eprinttype = {pmid},
pages = {185--197},
issn = {1535-6108, 1878-3686},
doi = {10.1016/S1535-6108(03)00028-X},
url = {https://www.cell.com/cancer-cell/abstract/S1535-6108(03)00028-X},
urldate = {2019-12-21},
langid = {english}
}
@article{rosenwaldUseMolecularProfiling2002,
title = {The {{Use}} of {{Molecular Profiling}} to {{Predict Survival}} after {{Chemotherapy}} for {{Diffuse Large-B-Cell Lymphoma}}},
author = {Rosenwald, Andreas and Wright, George and Chan, Wing C and Connors, Joseph M and Campo, Elias and Fisher, Richard I and Gascoyne, Randy D and Muller-Hermelink, H Konrad and Smeland, Erlend B and Giltnane, Jena M and Hurt, Elaine M and Zhao, Hong and Averett, Lauren and Yang, Liming and Wilson, Wyndham H and Jaffe, Elaine S and Simon, Richard and Klausner, Richard D and Powell, John and Duffey, Patricia L and Longo, Dan L and Greiner, Timothy C and Weisenburger, Dennis D and Sanger, Warren G and Dave, Bhavana J and Lynch, James C and Vose, Julie and Armitage, James O and Montserrat, Emilio and López-Guillermo, Armando and Grogan, Thomas M and Miller, Thomas P and LeBlanc, Michel and Ott, German and Kvaloy, Stein and Delabie, Jan and Holte, Harald and Krajci, Peter and Stokke, Trond and Staudt, Louis M},
date = {2002-06},
journaltitle = {N Engl J Med},
volume = {346},
number = {25},
pages = {1937--1947}
}
@article{rossbachAutoCrossRegulationHnRNP2009,
title = {Auto- and {{Cross-Regulation}} of the {{hnRNP L Proteins}} by {{Alternative Splicing}}},
author = {Rossbach, Oliver and Hung, Lee-Hsueh and Schreiner, Silke and Grishina, Inna and Heiner, Monika and Hui, Jingyi and Bindereif, Albrecht},
date = {2009-03-15},
journaltitle = {Molecular and Cellular Biology},
volume = {29},
number = {6},
eprint = {19124611},
eprinttype = {pmid},
pages = {1442--1451},
issn = {0270-7306, 1098-5549},
doi = {10.1128/MCB.01689-08},
url = {https://mcb.asm.org/content/29/6/1442},
urldate = {2019-12-21},
abstract = {We recently characterized human hnRNP L as a global regulator of alternative splicing, binding to CA-repeat and CA-rich elements. Here we report that hnRNP L autoregulates its own expression on the level of alternative splicing. Intron 6 of the human hnRNP L gene contains a short exon that, if used, introduces a premature termination codon, resulting in nonsense-mediated decay (NMD). This “poison exon” is preceded by a highly conserved CA-rich cluster extending over 800 nucleotides that binds hnRNP L and functions as an unusually extended, intronic enhancer, promoting inclusion of the poison exon. As a result, excess hnRNP L activates NMD of its own mRNA, thereby creating a negative autoregulatory feedback loop and contributing to homeostasis of hnRNP L levels. We present experimental evidence for this mechanism, based on NMD inactivation, hnRNP L binding assays, and hnRNP L-dependent alternative splicing of heterologous constructs. In addition, we demonstrate that hnRNP L cross-regulates inclusion of an analogous poison exon in the hnRNP L-like pre-mRNA, which explains the reciprocal expression of the two closely related hnRNP L proteins.},
langid = {english}
}
@article{rossi2006,
title = {1},
author = {Rossi, D and Berra, E and Cerri, M and Deambrogi, C and Barbieri, C and Franceschetti, S and Lunghi, M and Conconi, A and Paulli, M and Matolcsy, A and Pasqualucci, L and Capello, D and Gaidano, G},
date = {2006-10},
journaltitle = {Haematologica},
volume = {91},
number = {10},
pages = {1405--1409}
}
@article{rossiAlterationBIRC3Multiple2011,
title = {Alteration of {{BIRC3}} and Multiple Other {{NF-κB}} Pathway Genes in Splenic Marginal Zone Lymphoma},
author = {Rossi, Davide and Deaglio, Silvia and Dominguez-Sola, David and Rasi, Silvia and Vaisitti, Tiziana and Agostinelli, Claudio and Spina, Valeria and Bruscaggin, Alessio and Monti, Sara and Cerri, Michaela and Cresta, Stefania and Fangazio, Marco and Arcaini, Luca and Lucioni, Marco and Marasca, Roberto and Thieblemont, Catherine and Capello, Daniela and Facchetti, Fabio and Kwee, Ivo and Pileri, Stefano A. and Foà, Robin and Bertoni, Francesco and Dalla-Favera, Riccardo and Pasqualucci, Laura and Gaidano, Gianluca},
date = {2011-11-03},
journaltitle = {Blood},
shortjournal = {Blood},
volume = {118},
number = {18},
eprint = {21881048},
eprinttype = {pmid},
pages = {4930--4934},
issn = {1528-0020},
doi = {10.1182/blood-2011-06-359166},
abstract = {Splenic marginal zone lymphoma (SMZL) is one of the few B-cell lymphoma types that remain orphan of molecular lesions in cancer-related genes. Detection of active NF-κB signaling in 14 (58\%) of 24 SMZLs prompted the investigation of NF-κB molecular alterations in 101 SMZLs. Mutations and copy number abnormalities of NF-κB genes occurred in 36 (36\%) of 101 SMZLs and targeted both canonical (TNFAIP3 and IKBKB) and noncanonical (BIRC3, TRAF3, MAP3K14) NF-κB pathways. Most alterations were mutually exclusive, documenting the existence of multiple independent mechanisms affecting NF-κB in SMZL. BIRC3 inactivation in SMZL recurred because of somatic mutations that disrupted the same RING domain that in extranodal marginal zone lymphoma is removed by the t(11;18) translocation, which points to BIRC3 disruption as a common mechanism across marginal zone B-cell lymphomagenesis. Genetic lesions of NF-κB provide a molecular basis for the pathogenesis of more than 30\% of SMZLs and offer a suitable target for NF-κB therapeutic approaches in this lymphoma.},
langid = {english},
keywords = {Baculoviral IAP Repeat-Containing 3 Protein,Case-Control Studies,Cluster Analysis,DNA Mutational Analysis,Gene Expression Profiling,Gene Expression Regulation Neoplastic,Humans,Inhibitor of Apoptosis Proteins,Lymphoma B-Cell Marginal Zone,Microarray Analysis,Models Biological,NF-kappa B,Signal Transduction,Splenic Neoplasms,Ubiquitin-Protein Ligases}
}
@article{rossiCodingGenomeSplenic2012,
title = {The Coding Genome of Splenic Marginal Zone Lymphoma: Activation of {{NOTCH2}} and Other Pathways Regulating Marginal Zone Development},
shorttitle = {The Coding Genome of Splenic Marginal Zone Lymphoma},
author = {Rossi, Davide and Trifonov, Vladimir and Fangazio, Marco and Bruscaggin, Alessio and Rasi, Silvia and Spina, Valeria and Monti, Sara and Vaisitti, Tiziana and Arruga, Francesca and Famà, Rosella and Ciardullo, Carmela and Greco, Mariangela and Cresta, Stefania and Piranda, Daniela and Holmes, Antony and Fabbri, Giulia and Messina, Monica and Rinaldi, Andrea and Wang, Jiguang and Agostinelli, Claudio and Piccaluga, Pier Paolo and Lucioni, Marco and Tabbò, Fabrizio and Serra, Roberto and Franceschetti, Silvia and Deambrogi, Clara and Daniele, Giulia and Gattei, Valter and Marasca, Roberto and Facchetti, Fabio and Arcaini, Luca and Inghirami, Giorgio and Bertoni, Francesco and Pileri, Stefano A. and Deaglio, Silvia and Foà, Robin and Dalla-Favera, Riccardo and Pasqualucci, Laura and Rabadan, Raul and Gaidano, Gianluca},
date = {2012-08-27},
journaltitle = {The Journal of Experimental Medicine},
shortjournal = {J Exp Med},
volume = {209},
number = {9},
eprint = {22891273},
eprinttype = {pmid},
pages = {1537--1551},
issn = {1540-9538},
doi = {10.1084/jem.20120904},
abstract = {Splenic marginal zone lymphoma (SMZL) is a B cell malignancy of unknown pathogenesis, and thus an orphan of targeted therapies. By integrating whole-exome sequencing and copy-number analysis, we show that the SMZL exome carries at least 30 nonsilent gene alterations. Mutations in NOTCH2, a gene required for marginal-zone (MZ) B cell development, represent the most frequent lesion in SMZL, accounting for ∼20\% of cases. All NOTCH2 mutations are predicted to cause impaired degradation of the NOTCH2 protein by eliminating the C-terminal PEST domain, which is required for proteasomal recruitment. Among indolent B cell lymphoproliferative disorders, NOTCH2 mutations are restricted to SMZL, thus representing a potential diagnostic marker for this lymphoma type. In addition to NOTCH2, other modulators or members of the NOTCH pathway are recurrently targeted by genetic lesions in SMZL; these include NOTCH1, SPEN, and DTX1. We also noted mutations in other signaling pathways normally involved in MZ B cell development, suggesting that deregulation of MZ B cell development pathways plays a role in the pathogenesis of ∼60\% SMZL. These findings have direct implications for the treatment of SMZL patients, given the availability of drugs that can target NOTCH, NF-κB, and other pathways deregulated in this disease.},
langid = {english},
pmcid = {PMC3428941},
keywords = {B-Lymphocytes,Chromatin Assembly and Disassembly,DNA-Binding Proteins,Exome,Gene Expression Regulation Neoplastic,Homeodomain Proteins,Humans,Lymphoma B-Cell,Mutation,NF-kappa B,Nuclear Proteins,Polymorphism Single Nucleotide,Receptor Notch1,Receptor Notch2,RNA-Binding Proteins,Signal Transduction,Splenic Neoplasms}
}
@article{rossiMutationsSF3B1Splicing2011,
title = {Mutations of the {{SF3B1}} Splicing Factor in Chronic Lymphocytic Leukemia: Association with Progression and Fludarabine-Refractoriness},
shorttitle = {Mutations of the {{SF3B1}} Splicing Factor in Chronic Lymphocytic Leukemia},
author = {Rossi, Davide and Bruscaggin, Alessio and Spina, Valeria and Rasi, Silvia and Khiabanian, Hossein and Messina, Monica and Fangazio, Marco and Vaisitti, Tiziana and Monti, Sara and Chiaretti, Sabina and Guarini, Anna and Del Giudice, Ilaria and Cerri, Michaela and Cresta, Stefania and Deambrogi, Clara and Gargiulo, Ernesto and Gattei, Valter and Forconi, Francesco and Bertoni, Francesco and Deaglio, Silvia and Rabadan, Raul and Pasqualucci, Laura and Foà, Robin and Dalla-Favera, Riccardo and Gaidano, Gianluca},
date = {2011-12-22},
journaltitle = {Blood},
shortjournal = {Blood},
volume = {118},
number = {26},
eprint = {22039264},
eprinttype = {pmid},
pages = {6904--6908},
issn = {1528-0020},
doi = {10.1182/blood-2011-08-373159},
abstract = {The genetic lesions identified in chronic lymphocytic leukemia (CLL) do not entirely recapitulate the disease pathogenesis and the development of serious complications, such as chemorefractoriness. While investigating the coding genome of fludarabine-refractory CLL, we observed that mutations of SF3B1, encoding a splicing factor and representing a critical component of the cell spliceosome, were recurrent in 10 of 59 (17\%) fludarabine-refractory cases, with a frequency significantly greater than that observed in a consecutive CLL cohort sampled at diagnosis (17/301, 5\%; P = .002). Mutations were somatically acquired, were generally represented by missense nucleotide changes, clustered in selected HEAT repeats of the SF3B1 protein, recurrently targeted 3 hotspots (codons 662, 666, and 700), and were predictive of a poor prognosis. In fludarabine-refractory CLL, SF3B1 mutations and TP53 disruption distributed in a mutually exclusive fashion (P = .046). The identification of SF3B1 mutations points to splicing regulation as a novel pathogenetic mechanism of potential clinical relevance in CLL.},
langid = {english},
pmcid = {PMC3245210},
keywords = {Amino Acid Sequence,Antineoplastic Agents,Disease Progression,DNA Mutational Analysis,Drug Resistance Neoplasm,Gene Expression Profiling,Gene Expression Regulation Leukemic,Humans,In Situ Hybridization Fluorescence,Karyotyping,Leukemia Lymphocytic Chronic B-Cell,Molecular Sequence Data,Mutation,Oligonucleotide Array Sequence Analysis,Phosphoproteins,Polymorphism Single Nucleotide,Ribonucleoprotein U2 Small Nuclear,RNA Splicing Factors,Sequence Homology Amino Acid,Spliceosomes,Tumor Suppressor Protein p53,Vidarabine}
}
@article{rothrockHnRNPRepressesExon2005,
title = {{{HnRNP L}} Represses Exon Splicing via a Regulated Exonic Splicing Silencer},
author = {Rothrock, Caryn R and House, Amy E and Lynch, Kristen W},
date = {2005-08-03},
journaltitle = {The EMBO Journal},
volume = {24},
number = {15},
pages = {2792--2802},
publisher = {John Wiley \& Sons, Ltd},
issn = {0261-4189},
doi = {10.1038/sj.emboj.7600745},
url = {https://www.embopress.org/doi/full/10.1038/sj.emboj.7600745},
urldate = {2022-09-27},
abstract = {Skipping of mammalian exons during pre-mRNA splicing is commonly mediated by the activity of exonic splicing silencers (ESSs). We have recently identified a regulated ESS within variable exon 4 of the CD45 gene, named ESS1, that is necessary and sufficient for partial exon repression in resting T cells and has additional silencing activity upon T-cell activation. In this study, we identify three heterogeneous nuclear ribonucleoproteins (hnRNPs) that bind specifically to ESS1. The binding of one of these proteins, hnRNP-L, is significantly decreased by mutations that disrupt both the basal and induced activities of ESS1. Recombinant hnRNP-L functions to repress exon inclusion in vitro in an ESS1-dependent manner. Moreover, depletion of hnRNP-L, either in vitro or in vivo, leads to increased exon inclusion. In contrast, the other ESS1-binding proteins, PTB and hnRNP E2, do not discriminate between wild-type and mutant ESS1 in binding studies, and do not specifically alter ESS1-dependent splicing in vitro. Together, these studies demonstrate that hnRNP-L is the primary protein through which CD45 exon 4 silencing is mediated by the regulatory sequence ESS1.},
keywords = {alternative splicing,CD45,ESS,hnRNP}
}
@article{roulland1418Translocation2014,
title = {T(14;18) {{Translocation}}: {{A}} Predictive Blood Biomarker for Follicular Lymphoma},
shorttitle = {T(14;18) {{Translocation}}},
author = {Roulland, Sandrine and Kelly, Rachel S. and Morgado, Ester and Sungalee, Stéphanie and Solal-Celigny, Philippe and Colombat, Philippe and Jouve, Nathalie and Palli, Domenico and Pala, Valeria and Tumino, Rosario and Panico, Salvatore and Sacerdote, Carlotta and Quirós, José R. and Gonzáles, Carlos A. and Sánchez, Maria-José and Dorronsoro, Miren and Navarro, Carmen and Barricarte, Aurelio and Tjønneland, Anne and Olsen, Anja and Overvad, Kim and Canzian, Federico and Kaaks, Rudolf and Boeing, Heiner and Drogan, Dagmar and Nieters, Alexandra and Clavel-Chapelon, Françoise and Trichopoulou, Antonia and Trichopoulos, Dimitrios and Lagiou, Pagona and Bueno-de-Mesquita, H. Bas and Peeters, Petra H. M. and Vermeulen, Roel and Hallmans, Göran and Melin, Beatrice and Borgquist, Signe and Carlson, Joyce and Lund, Eiliv and Weiderpass, Elisabete and Khaw, Kay-Tee and Wareham, Nick and Key, Timothy J. and Travis, Ruth C. and Ferrari, Pietro and Romieu, Isabelle and Riboli, Elio and Salles, Gilles and Vineis, Paolo and Nadel, Bertrand},
date = {2014-05-01},
journaltitle = {Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology},
shortjournal = {J Clin Oncol},
volume = {32},
number = {13},
eprint = {24687831},
eprinttype = {pmid},
pages = {1347--1355},
issn = {1527-7755},
doi = {10.1200/JCO.2013.52.8190},
abstract = {PURPOSE: The (14;18) translocation constitutes both a genetic hallmark and critical early event in the natural history of follicular lymphoma (FL). However, t(14;18) is also detectable in the blood of otherwise healthy persons, and its relationship with progression to disease remains unclear. Here we sought to determine whether t(14;18)-positive cells in healthy individuals represent tumor precursors and whether their detection could be used as an early predictor for FL. PARTICIPANTS AND METHODS: Among 520,000 healthy participants enrolled onto the EPIC (European Prospective Investigation Into Cancer and Nutrition) cohort, we identified 100 who developed FL 2 to 161 months after enrollment. Prediagnostic blood from these and 218 controls were screened for t(14;18) using sensitive polymerase chain reaction-based assays. Results were subsequently validated in an independent cohort (65 case participants; 128 controls). Clonal relationships between t(14;18) cells and FL were also assessed by molecular backtracking of paired prediagnostic blood and tumor samples. RESULTS: Clonal analysis of t(14;18) junctions in paired prediagnostic blood versus tumor samples demonstrated that progression to FL occurred from t(14;18)-positive committed precursors. Furthermore, healthy participants at enrollment who developed FL up to 15 years later showed a markedly higher t(14;18) prevalence and frequency than controls (P {$<$} .001). Altogether, we estimated a 23-fold higher risk of subsequent FL in blood samples associated with a frequency {$>$} 10(-4) (odds ratio, 23.17; 95\% CI, 9.98 to 67.31; P {$<$} .001). Remarkably, risk estimates remained high and significant up to 15 years before diagnosis. CONCLUSION: High t(14;18) frequency in blood from healthy individuals defines the first predictive biomarker for FL, effective years before diagnosis.},
langid = {english},
keywords = {Adult,Aged,Biomarkers Tumor,Case-Control Studies,Chromosomes Human Pair 14,Chromosomes Human Pair 18,Cohort Studies,Europe,Female,Humans,Lymphoma Follicular,Male,Middle Aged,Molecular Epidemiology,Polymerase Chain Reaction,Prevalence,Translocation Genetic}
}
@article{rungeApplicationLymphGenClassification2021,
title = {Application of the {{LymphGen}} Classification Tool to 928 Clinically and Genetically-Characterised Cases of Diffuse Large {{B}} Cell Lymphoma ({{DLBCL}})},
author = {Runge, Hendrik F. P. and Lacy, Stuart and Barrans, Sharon and Beer, Philip A and Painter, Daniel and Smith, Alexandra and Roman, Eve and Burton, Cathy and Crouch, Simon and Tooze, Reuben and Hodson, Daniel J.},
date = {2021},
journaltitle = {British Journal of Haematology},
volume = {192},
number = {1},
pages = {216--220},
issn = {1365-2141},
doi = {10.1111/bjh.17132},
url = {https://onlinelibrary.wiley.com/doi/abs/10.1111/bjh.17132},
urldate = {2023-01-16},
langid = {english}
}
@article{rushtonGeneticEvolutionaryPatterns2020,
title = {Genetic and Evolutionary Patterns of Treatment Resistance in Relapsed {{B-cell}} Lymphoma},
author = {Rushton, Christopher K. and Arthur, Sarah E. and Alcaide, Miguel and Cheung, Matthew and Jiang, Aixiang and Coyle, Krysta M. and Cleary, Kirstie L. S. and Thomas, Nicole and Hilton, Laura K. and Michaud, Neil and Daigle, Scott and Davidson, Jordan and Bushell, Kevin and Yu, Stephen and Rys, Ryan N. and Jain, Michael and Shepherd, Lois and Marra, Marco A. and Kuruvilla, John and Crump, Michael and Mann, Koren and Assouline, Sarit and Connors, Joseph M. and Steidl, Christian and Cragg, Mark S. and Scott, David W. and Johnson, Nathalie A. and Morin, Ryan D.},
date = {2020-07-14},
journaltitle = {Blood Advances},
shortjournal = {Blood Adv},
volume = {4},
number = {13},
eprint = {32589730},
eprinttype = {pmid},
pages = {2886--2898},
issn = {2473-9537},
doi = {10.1182/bloodadvances.2020001696},
abstract = {Diffuse large B-cell lymphoma (DLBCL) patients are typically treated with immunochemotherapy containing rituximab (rituximab, cyclophosphamide, hydroxydaunorubicin-vincristine (Oncovin), and prednisone [R-CHOP]); however, prognosis is extremely poor if R-CHOP fails. To identify genetic mechanisms contributing to primary or acquired R-CHOP resistance, we performed target-panel sequencing of 135 relapsed/refractory DLBCLs (rrDLBCLs), primarily comprising circulating tumor DNA from patients on clinical trials. Comparison with a metacohort of 1670 diagnostic DLBCLs identified 6 genes significantly enriched for mutations upon relapse. TP53 and KMT2D were mutated in the majority of rrDLBCLs, and these mutations remained clonally persistent throughout treatment in paired diagnostic-relapse samples, suggesting a role in primary treatment resistance. Nonsense and missense mutations affecting MS4A1, which encodes CD20, are exceedingly rare in diagnostic samples but show recurrent patterns of clonal expansion following rituximab-based therapy. MS4A1 missense mutations within the transmembrane domains lead to loss of CD20 in vitro, and patient tumors harboring these mutations lacked CD20 protein expression. In a time series from a patient treated with multiple rounds of therapy, tumor heterogeneity and minor MS4A1-harboring subclones contributed to rapid disease recurrence, with MS4A1 mutations as founding events for these subclones. TP53 and KMT2D mutation status, in combination with other prognostic factors, may be used to identify high-risk patients prior to R-CHOP for posttreatment monitoring. Using liquid biopsies, we show the potential to identify tumors with loss of CD20 surface expression stemming from MS4A1 mutations. Implementation of noninvasive assays to detect such features of acquired treatment resistance may allow timely transition to more effective treatment regimens.},
langid = {english},
pmcid = {PMC7362366},
keywords = {Antibodies Monoclonal Murine-Derived,Antineoplastic Combined Chemotherapy Protocols,Humans,Lymphoma Large B-Cell Diffuse,Morinlab,Neoplasm Recurrence Local,Rituximab}
}
@article{russler-germainMutationsAssociatedProgression2023,
title = {Mutations Associated with Progression in Follicular Lymphoma Predict Inferior Outcomes at Diagnosis: {{Alliance A151303}}},
author = {Russler-Germain, David A. and Krysiak, Kilannin and Ramirez, Cody A. and Mosior, Matthew and Watkins, Marcus P. and Gomez, Felicia and Skidmore, Zachary L. and Trani, L. and Gao, F. and Geyer, Susan and Cashen, A. and Mehta-Shah, N. and Kahl, B. and Bartlett, N. and Alderuccio, J. and Lossos, I. and Ondrejka, S. and Hsi, E. and Martin, P. and Leonard, J. and Griffith, M. and Griffith, O. and Fehniger, T.},
date = {2023},
journaltitle = {Blood Advances},
shortjournal = {Blood Advances},
volume = {7},
pages = {5524--5539},
doi = {10.1182/bloodadvances.2023010779}
}
@article{russoHnRNPH1Intronic2010,
title = {{{hnRNP H1}} and Intronic {{G}} Runs in the Splicing Control of the Human {{rpL3}} Gene},
author = {Russo, Annapina and Siciliano, Gabriella and Catillo, Morena and Giangrande, Chiara and Amoresano, Angela and Pucci, Pietro and Pietropaolo, Concetta and Russo, Giulia},
date = {2010-05-01},
journaltitle = {Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms},
shortjournal = {Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms},
volume = {1799},
number = {5},
pages = {419--428},
issn = {1874-9399},
doi = {10.1016/j.bbagrm.2010.01.008},
url = {https://www.sciencedirect.com/science/article/pii/S1874939910000192},
urldate = {2022-09-28},
abstract = {By generating mRNA containing a premature termination codon (PTC), alternative splicing (AS) can quantitatively regulate the expression of genes that are degraded by nonsense-mediated mRNA decay (NMD). We previously demonstrated that AS-induced retention of part of intron 3 of rpL3 pre-mRNA produces an mRNA isoform that contains a PTC and is targeted for decay by NMD. We also demonstrated that overexpression of rpL3 downregulates canonical splicing and upregulates the alternative splicing of its pre-mRNA. We are currently investigating the molecular mechanism underlying rpL3 autoregulation. Here we report that the heterogeneous nuclear ribonucleoprotein (hnRNP) H1 is a transacting factor able to interact in vitro and in vivo with rpL3 and with intron 3 of the rpL3 gene. We investigated the role played by hnRNP H1 in the regulation of splicing of rpL3 pre-mRNA by manipulating its expression level. Depletion of hnRNP H1 reduced the level of the PTC-containing mRNA isoform, whereas its overexpression favored the selection of the cryptic 3′ splice site of intron 3. We also identified and characterized the cis-acting regulatory elements involved in hnRNP H1-mediated regulation of splicing. RNA electromobility shift assay demonstrated that hnRNP H1 specifically recognizes and binds directly to the intron 3 region that contains seven copies of G-rich elements. Site-directed mutagenesis analysis and in vivo studies showed that the G3 and G6 elements are required for hnRNP H1-mediated regulation of rpL3 pre-mRNA splicing. We propose a working model in which rpL3 recruits hnRNP H1 and, through cooperation with other splicing factors, promotes selection of the alternative splice site.},
langid = {english},
keywords = {Alternative splicing,hnRNP H1,NMD,Ribosomal protein,Splicing regulation}
}
@article{sadriAUF1InvolvedSplenic2010,
title = {{{AUF1}} Is Involved in Splenic Follicular {{B}} Cell Maintenance},
author = {Sadri, Navid and Lu, Jin-Yu and Badura, Michelle L. and Schneider, Robert J.},
date = {2010-01-11},
journaltitle = {BMC Immunology},
shortjournal = {BMC Immunology},
volume = {11},
number = {1},
pages = {1},
issn = {1471-2172},
doi = {10.1186/1471-2172-11-1},
url = {https://doi.org/10.1186/1471-2172-11-1},
urldate = {2022-10-04},
abstract = {The adenosine/uridine-rich element (ARE)-binding protein AUF1 functions to regulate the inflammatory response through the targeted degradation of cytokine and other mRNAs that contain specific AREs in their 3' noncoding region (3' NCR). To investigate the role of AUF1 in the immune system, we characterized the lymphoid compartments of AUF1-deficient mice.},
keywords = {CD40 Engagement,Class Switch Recombination,Germinal Center,Marginal Zone,Splenic Lymphocyte}
}
@article{sahaTranscriptomicAnalysisIdentifies2019,
title = {Transcriptomic {{Analysis Identifies RNA Binding Proteins}} as {{Putative Regulators}} of {{Myelopoiesis}} and {{Leukemia}}},
author = {Saha, Subha and Murmu, Krushna Chandra and Biswas, Mayukh and Chakraborty, Sohini and Basu, Jhinuk and Madhulika, Swati and Kolapalli, Srinivasa Prasad and Chauhan, Santosh and Sengupta, Amitava and Prasad, Punit},
date = {2019},
journaltitle = {Frontiers in Oncology},
shortjournal = {Front. Oncol.},
volume = {9},
issn = {2234-943X},
doi = {10.3389/fonc.2019.00692},
url = {https://www.frontiersin.org/articles/10.3389/fonc.2019.00692/full},
urldate = {2019-12-21},
abstract = {Acute myeloid leukemia (AML) is a common and aggressive hematological malignancy. Acquisition of heterogeneous genetic aberrations and epigenetic dysregulation lead to the transformation of hematopoietic stem cells (HSC) into leukemic stem cells (LSC), which subsequently gives rise to immature blast cells and a leukemic phenotype. LSCs are responsible for disease relapse as current chemotherapeutic regimens are not able to completely eradicate these cellular sub-populations. Therefore, it is critical to improve upon the existing knowledge of LSC specific markers, which would allow for specific targeting of these cells more effectively. Although significant milestones in decoding the aberrant transcriptional network of various cancers, including leukemia, have been achieved, studies on the involvement of post-transcriptional gene regulation (PTGR) in disease progression are beginning to unfold. RNA binding proteins (RBPs), are key players in mediating PTGR and they regulate the intracellular fate of individual transcripts, from their biogenesis to RNA metabolism. In this study, we have used an integrative approach to systematically profile RBP expression and identify key regulatory RBPs involved in normal myeloid development and AML. We have analyzed RNA-seq datasets (GSE74246) of HSCs, common myeloid progenitors (CMPs), granulocyte-macrophage progenitors (GMPs), monocytes, LSCs, and blasts. We observed that normal and leukemic cells can be distinguished on the basis of RBP expression, which is indicative of cell type specific expression. We identified that distinctly co-expressing modules of RBPs and their subclasses were enriched in hematopoietic stem/progenitor (HSCP) and differentiated monocytes. We detected expression of DZIP3, an E3 ubiquitin ligase, in HSCP, knockdown of which promotes monocytic differentiation in cell line model. We identified co-expression modules of RBP genes in LSCs and among these, distinct modules of RBP genes with high and low expression. The expression of several AML-specific RBPs were validated byqRT-PCR. Network analysis identified densely connected hubs of ribosomal RBP genes (rRBPs) with low expression in LSCs, suggesting the dependency of LSCs on altered ribosome dynamics. In conclusion, our systematic analysis elucidates the RBP transcriptomic landscape in normal and malignant myelopoiesis, and highlights the functional consequences that may result from perturbation of RBP gene expression in these cellular landscapes.},
langid = {english}
}
@article{sakrIdentificationDoubleHit2019,
title = {Identification of "{{Double Hit}}" {{Lymphomas Using Updated WHO Criteria}}: {{Insights From Routine MYC Immunohistochemistry}} in 272 {{Consecutive Cases}} of {{Aggressive B-Cell Lymphomas}}},
shorttitle = {Identification of "{{Double Hit}}" {{Lymphomas Using Updated WHO Criteria}}},
author = {Sakr, Hany and Cook, James R.},
date = {2019-07},
journaltitle = {Applied immunohistochemistry \& molecular morphology: AIMM},
shortjournal = {Appl. Immunohistochem. Mol. Morphol.},
volume = {27},
number = {6},
eprint = {29629947},
eprinttype = {pmid},
pages = {410--415},
issn = {1533-4058},
doi = {10.1097/PAI.0000000000000657},
abstract = {Aggressive lymphomas with MYC and BCL2 and/or BCL6 translocations ("double hit" lymphomas, DHL) represent a distinct diagnostic category in the updated World Health Organization (WHO) classification. The diagnostic yield of MYC immunohistochemistry (IHC) for the identification of DHL is currently uncertain. MYC IHC was performed in 272 consecutive cases of aggressive B-cell lymphoma, and results correlated with fluorescence in situ hybridization (FISH) for MYC translocations. Among 156 patients with IHC and FISH data, MYC IHC identified MYC translocations with 89\% sensitivity, 38\% specificity, 92\% negative predictive value, and 29\% positive predictive value. Three of 15 (20\%) of DHL were MYC IHC negative. One case contained a MYC translocation detectable IGH/MYC fusion probes but not MYC break-apart probes. A subset of DHL lack MYC protein expression, and recognition of this subset of cases requires FISH testing. These results provide an appropriate diagnostic algorithm for implementation of 2016 WHO diagnostic criteria.},
langid = {english}
}
@article{salaverriaRecurrent11qAberration2014,
title = {A Recurrent 11q Aberration Pattern Characterizes a Subset of {{MYC-negative}} High-Grade {{B-cell}} Lymphomas Resembling {{Burkitt}} Lymphoma},
author = {Salaverria, Itziar and Martin-Guerrero, Idoia and Wagener, Rabea and Kreuz, Markus and Kohler, Christian W. and Richter, Julia and Pienkowska-Grela, Barbara and Adam, Patrick and Burkhardt, Birgit and Claviez, Alexander and Damm-Welk, Christine and Drexler, Hans G. and Hummel, Michael and Jaffe, Elaine S. and Küppers, Ralf and Lefebvre, Christine and Lisfeld, Jasmin and Löffler, Markus and Macleod, Roderick A. F. and Nagel, Inga and Oschlies, Ilske and Rosolowski, Maciej and Russell, Robert B. and Rymkiewicz, Grzegorz and Schindler, Detlev and Schlesner, Matthias and Scholtysik, René and Schwaenen, Carsten and Spang, Rainer and Szczepanowski, Monika and Trümper, Lorenz and Vater, Inga and Wessendorf, Swen and Klapper, Wolfram and Siebert, Reiner and {Molecular Mechanisms in Malignant Lymphoma Network Project} and {Berlin-Frankfurt-Münster Non-Hodgkin Lymphoma Group}},
date = {2014-02-20},
journaltitle = {Blood},
shortjournal = {Blood},
volume = {123},
number = {8},
eprint = {24398325},
eprinttype = {pmid},
pages = {1187--1198},
issn = {1528-0020},
doi = {10.1182/blood-2013-06-507996},
abstract = {The genetic hallmark of Burkitt lymphoma (BL) is the t(8;14)(q24;q32) and its variants leading to activation of the MYC oncogene. It is a matter of debate whether true BL without MYC translocation exists. Here, we identified 59 lymphomas concordantly called BL by 2 gene expression classifiers among 753 B-cell lymphomas. Only 2 (3\%) of these 59 molecular BL lacked a MYC translocation, which both shared a peculiar pattern of chromosome 11q aberration characterized by interstitial gains including 11q23.2-q23.3 and telomeric losses of 11q24.1-qter. We extended our analysis to 17 MYC-negative high-grade B-cell lymphomas with a similar 11q aberration and showed this aberration to be recurrently associated with morphologic and clinical features of BL. The minimal region of gain was defined by high-level amplifications in 11q23.3 and associated with overexpression of genes including PAFAH1B2 on a transcriptional and protein level. The recurrent region of loss contained a focal homozygous deletion in 11q24.2-q24.3 including the ETS1 gene, which was shown to be mutated in 4 of 16 investigated cases. These findings indicate the existence of a molecularly distinct subset of B-cell lymphomas reminiscent of BL, which is characterized by deregulation of genes in 11q.},
langid = {english},
pmcid = {PMC3931189},
keywords = {Adolescent,Adult,Aged,B-Lymphocytes,Burkitt Lymphoma,Cell Line,Child,Chromosomes Human Pair 11,Chromosomes Human Pair 14,Chromosomes Human Pair 8,Female,Gene Expression Regulation Neoplastic,Genes myc,Humans,Male,Neoplasm Grading,Recurrence,Translocation Genetic,Young Adult}
}
@article{salehiCancerPhylogeneticTree2021,
title = {Cancer Phylogenetic Tree Inference at Scale from 1000s of Single Cell Genomes},
author = {Salehi, Sohrab and Dorri, Fatemeh and Chern, Kevin and Kabeer, Farhia and Rusk, Nicole and Funnell, Tyler and Williams, Marc J. and Lai, Daniel and Andronescu, Mirela and Campbell, Kieran R. and McPherson, Andrew and Aparicio, Samuel and Roth, Andrew and Shah, Sohrab and Bouchard-Côté, Alexandre},
date = {2021-09-04},
pages = {2020.05.06.058180},
publisher = {bioRxiv},
doi = {10.1101/2020.05.06.058180},
url = {https://www.biorxiv.org/content/10.1101/2020.05.06.058180v2},
urldate = {2022-02-01},
abstract = {A new generation of scalable single cell whole genome sequencing (scWGS) methods allows unprecedented high resolution measurement of the evolutionary dynamics of cancer cell populations. Phylogenetic reconstruction is central to identifying sub-populations and distinguishing the mutational processes that gave rise to them. Existing phylogenetic tree building models do not scale to the tens of thousands of high resolution genomes achievable with current scWGS methods. We constructed a phylogenetic model and associated Bayesian inference procedure, sitka, specifically for scWGS data. The method is based on a novel phylogenetic encoding of copy number (CN) data, the sitka transformation, that simplifies the site dependencies induced by rearrangements while still forming a sound foundation to phylogenetic inference. The sitka transformation allows us to design novel scalable Markov chain Monte Carlo (MCMC) algorithms. Moreover, we introduce a novel point mutation calling method that incorporates the CN data and the underlying phylogenetic tree to overcome the low per-cell coverage of scWGS. We demonstrate our method on three single cell datasets, including a novel PDX series, and analyse the topological properties of the inferred trees. Sitka is freely available at https://github.com/UBC-Stat-ML/sitkatree.git.},
langid = {english}
}
@article{salehiClonalFitnessInferred2021,
title = {Clonal Fitness Inferred from Time-Series Modelling of Single-Cell Cancer Genomes},
author = {Salehi, Sohrab and Kabeer, Farhia and Ceglia, Nicholas and Andronescu, Mirela and Williams, Marc J. and Campbell, Kieran R. and Masud, Tehmina and Wang, Beixi and Biele, Justina and Brimhall, Jazmine and Gee, David and Lee, Hakwoo and Ting, Jerome and Zhang, Allen W. and Tran, Hoa and O'Flanagan, Ciara and Dorri, Fatemeh and Rusk, Nicole and family=Algara, given=Teresa Ruiz, prefix=de, useprefix=true and Lee, So Ra and Cheng, Brian Yu Chieh and Eirew, Peter and Kono, Takako and Pham, Jenifer and Grewal, Diljot and Lai, Daniel and Moore, Richard and Mungall, Andrew J. and Marra, Marco A. and {IMAXT Consortium} and McPherson, Andrew and Bouchard-Côté, Alexandre and Aparicio, Samuel and Shah, Sohrab P.},
date = {2021-07},
journaltitle = {Nature},
shortjournal = {Nature},
volume = {595},
number = {7868},
eprint = {34163070},
eprinttype = {pmid},
pages = {585--590},
issn = {1476-4687},
doi = {10.1038/s41586-021-03648-3},
abstract = {Progress in defining genomic fitness landscapes in cancer, especially those defined by copy number alterations (CNAs), has been impeded by lack of time-series single-cell sampling of polyclonal populations and temporal statistical models1-7. Here we generated 42,000 genomes from multi-year time-series single-cell whole-genome sequencing of breast epithelium and primary triple-negative breast cancer (TNBC) patient-derived xenografts (PDXs), revealing the nature of CNA-defined clonal fitness dynamics induced by TP53 mutation and cisplatin chemotherapy. Using a new Wright-Fisher population genetics model8,9 to infer clonal fitness, we found that TP53 mutation alters the fitness landscape, reproducibly distributing fitness over a larger number of clones associated with distinct CNAs. Furthermore, in TNBC PDX models with mutated TP53, inferred fitness coefficients from CNA-based genotypes accurately forecast experimentally enforced clonal competition dynamics. Drug treatment in three long-term serially passaged TNBC PDXs resulted in cisplatin-resistant clones emerging from low-fitness phylogenetic lineages in the untreated setting. Conversely, high-fitness clones from treatment-naive controls were eradicated, signalling an inversion of the fitness landscape. Finally, upon release of drug, selection pressure dynamics were reversed, indicating a fitness cost of treatment resistance. Together, our findings define clonal fitness linked to both CNA and therapeutic resistance in polyclonal tumours.},
langid = {english},
pmcid = {PMC8396073},
keywords = {Animals,Cell Line Tumor,Cisplatin,Clone Cells,DNA Copy Number Variations,Drug Resistance Neoplasm,Female,Genetic Fitness,Humans,Mice,Models Statistical,Neoplasm Transplantation,Triple Negative Breast Neoplasms,Tumor Suppressor Protein p53,Whole Genome Sequencing}
}
@article{salghettiDestructionMycUbiquitinmediated1999,
title = {Destruction of {{Myc}} by Ubiquitin-Mediated Proteolysis: Cancer-Associated and Transforming Mutations Stabilize {{Myc}}},
shorttitle = {Destruction of {{Myc}} by Ubiquitin-Mediated Proteolysis},
author = {Salghetti, Simone E. and Young Kim, So and Tansey, William P.},
date = {1999-02-01},
journaltitle = {The EMBO Journal},
shortjournal = {The EMBO Journal},
volume = {18},
number = {3},
pages = {717--726},
publisher = {John Wiley \& Sons, Ltd},
issn = {0261-4189},
doi = {10.1093/emboj/18.3.717},
url = {https://www.embopress.org/doi/full/10.1093/emboj/18.3.717},
urldate = {2021-04-29},
abstract = {The human proto-oncogene c-myc encodes a highly unstable transcription factor that promotes cell proliferation. Although the extreme instability of Myc plays an important role in preventing its accumulation in normal cells, little is known about how Myc is targeted for rapid destruction. Here, we have investigated mechanisms regulating the stability of Myc. We show that Myc is destroyed by ubiquitin-mediated proteolysis, and define two elements in Myc that oppositely regulate its stability: a transcriptional activation domain that promotes Myc destruction, and a region required for association with the POZ domain protein Miz-1 that stabilizes Myc. We also show that Myc is stabilized by cancer-associated and transforming mutations within its transcriptional activation domain. Our data reveal a complex network of interactions regulating Myc destruction, and imply that enhanced protein stability contributes to oncogenic transformation by mutant Myc proteins.},
keywords = {Miz-1,Myc,transcription,ubiquitin-mediated proteolysis}
}
@article{sallesPrognosticSignificanceImmunohistochemical2011,
title = {Prognostic Significance of Immunohistochemical Biomarkers in Diffuse Large {{B-cell}} Lymphoma: A Study from the {{Lunenburg Lymphoma Biomarker Consortium}}.},
author = {Salles, Gilles and family=Jong, given=Daphne, prefix=de, useprefix=true and Xie, Wanling and Rosenwald, Andreas and Chhanabhai, Mukesh and Gaulard, Philippe and Klapper, Wolfram and Calaminici, Maria and Sander, Birgitta and Thorns, Christoph and Campo, Elias and Molina, Thierry and Lee, Abigail and Pfreundschuh, Michael and Horning, Sandra and Lister, Andrew and Sehn, Laurie H and Raemaekers, John and Hagenbeek, Anton and Gascoyne, Randy D and Weller, Edie},
date = {2011-05},
journaltitle = {Blood}
}
@article{saltzmanRegulationAlternativeSplicing2011,
title = {Regulation of Alternative Splicing by the Core Spliceosomal Machinery},
author = {Saltzman, Arneet L. and Pan, Qun and Blencowe, Benjamin J.},
date = {2011-02-15},
journaltitle = {Genes \& Development},
shortjournal = {Genes Dev.},
volume = {25},
number = {4},
eprint = {21325135},
eprinttype = {pmid},
pages = {373--384},
issn = {0890-9369, 1549-5477},
doi = {10.1101/gad.2004811},
url = {http://genesdev.cshlp.org/content/25/4/373},
urldate = {2019-12-21},
abstract = {Alternative splicing (AS) plays a major role in the generation of proteomic diversity and in gene regulation. However, the role of the basal splicing machinery in regulating AS remains poorly understood. Here we show that the core snRNP (small nuclear ribonucleoprotein) protein SmB/B′ self-regulates its expression by promoting the inclusion of a highly conserved alternative exon in its own pre-mRNA that targets the spliced transcript for nonsense-mediated mRNA decay (NMD). Depletion of SmB/B′ in human cells results in reduced levels of snRNPs and a striking reduction in the inclusion levels of hundreds of additional alternative exons, with comparatively few effects on constitutive exon splicing levels. The affected alternative exons are enriched in genes encoding RNA processing and other RNA-binding factors, and a subset of these exons also regulate gene expression by activating NMD. Our results thus demonstrate a role for the core spliceosomal machinery in controlling an exon network that appears to modulate the levels of many RNA processing factors.},
langid = {english},
keywords = {alternative splicing,autoregulation,exon network,NMD,Sm proteins,snRNP}
}
@article{sanchez-martinQuadruplexLigandsCancer2021,
title = {Quadruplex {{Ligands}} in {{Cancer Therapy}}},
author = {Sanchez-Martin, Victoria and Soriano, Miguel and Garcia-Salcedo, Jose Antonio},
date = {2021-06-24},
journaltitle = {Cancers},
shortjournal = {Cancers (Basel)},
volume = {13},
number = {13},
eprint = {34202648},
eprinttype = {pmid},
pages = {3156},
issn = {2072-6694},
doi = {10.3390/cancers13133156},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267697/},
urldate = {2022-10-15},
abstract = {Simple Summary Four-stranded nucleic acid secondary structures (quadruplexes) including DNA G-quadruplexes, RNA G-quadruplexes and i-Motifs display key regulatory functions in the human genome. Quadruplexes play an important role in telomere lengthening and the expression control of several cancer-related genes. In this context, quadruplex ligands are considered as potential strategies for anticancer drug discovery. Previous reviews are mainly focused on ligands targeting DNA G-quadruplexes, RNA G-quadruplexes and i-Motifs in a separate way, hindering a holistic study. The present review overcomes this limitation by providing a general overview of the recent research on ligands targeting the three different quadruplex structures in cancer. Abstract Nucleic acids can adopt alternative secondary conformations including four-stranded structures known as quadruplexes. To date, quadruplexes have been demonstrated to exist both in human chromatin DNA and RNA. In particular, quadruplexes are found in guanine-rich sequences constituting G-quadruplexes, and in cytosine-rich sequences forming i-Motifs as a counterpart. Quadruplexes are associated with key biological processes ranging from transcription and translation of several oncogenes and tumor suppressors to telomeres maintenance and genome instability. In this context, quadruplexes have prompted investigations on their possible role in cancer biology and the evaluation of small-molecule ligands as potential therapeutic agents. This review aims to provide an updated close-up view of the literature on quadruplex ligands in cancer therapy, by grouping together ligands for DNA and RNA G-quadruplexes and DNA i-Motifs.},
pmcid = {PMC8267697}
}
@article{sanchezCoupledAlterationTranscription2008,
title = {Coupled Alteration of Transcription and Splicing by a Single Oncogene: {{Boosting}} the Effect on Cyclin {{D1}} Activity},
shorttitle = {Coupled Alteration of Transcription and Splicing by a Single Oncogene},
author = {Sanchez, Gabriel and Delattre, Olivier and Auboeuf, Didier and Dutertre, Martin},
date = {2008-08-01},
journaltitle = {Cell Cycle},
volume = {7},
number = {15},
eprint = {18677114},
eprinttype = {pmid},
pages = {2299--2305},
issn = {1538-4101},
doi = {10.4161/cc.6445},
url = {https://doi.org/10.4161/cc.6445},
urldate = {2019-12-21},
abstract = {In cancer cells, gene expression is altered at the levels of transcription and mRNA maturation, with many splice variants being associated with cancer. Splicing is tightly connected to transcription and can be affected by transcription elongation dynamics. Moreover, various transcriptional coregulators that are altered in cancer, such as the proto-oncogene EWS, are thought to play a role in splicing. A recent study shows that an alteration of EWS in Ewing sarcoma alters the dynamics of RNA polymerase II over the CCND1 proto-oncogene encoding cyclin D1, leading to an increase in its transcription and to an alteration of splicing that results in high levels of the oncogenic cyclin D1b splice isoform. The cyclin D1b isoform is highly expressed in Ewing sarcoma cells and tumors and stimulates Ewing sarcoma cell growth. Thus, alterations of transcriptional regulators in disease may lead to splicing alterations. We review these data and discuss how this concept may apply to various factors that are altered in cancer.}
}
@article{sapirHeterogeneousNuclearRibonucleoprotein,
title = {Heterogeneous Nuclear Ribonucleoprotein {{U}} ({{HNRNPU}}) Safeguards the Developing Mouse Cortex - {{PMC}}},
author = {Sapir, Tamar and Kshirsagar, Aditya and Gorelik, Anna},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9304408/},
urldate = {2023-01-09}
}
@article{sapirHeterogeneousNuclearRibonucleoprotein2022,
title = {Heterogeneous Nuclear Ribonucleoprotein {{U}} ({{HNRNPU}}) Safeguards the Developing Mouse Cortex},
author = {Sapir, Tamar and Kshirsagar, Aditya and Gorelik, Anna and Olender, Tsviya and Porat, Ziv and Scheffer, Ingrid E. and Goldstein, David B. and Devinsky, Orrin and Reiner, Orly},
date = {2022-07-21},
journaltitle = {Nature Communications},
shortjournal = {Nat Commun},
volume = {13},
eprint = {35864088},
eprinttype = {pmid},
pages = {4209},
issn = {2041-1723},
doi = {10.1038/s41467-022-31752-z},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9304408/},
urldate = {2023-01-09},
abstract = {HNRNPU encodes the heterogeneous nuclear ribonucleoprotein U, which participates in RNA splicing and chromatin organization. Microdeletions in the 1q44 locus encompassing HNRNPU and other genes and point mutations in HNRNPU cause brain disorders, including early-onset seizures and severe intellectual disability. We aimed to understand HNRNPU’s roles in the developing brain. Our work revealed that HNRNPU loss of function leads to rapid cell death of both postmitotic neurons and neural progenitors, with an apparent higher sensitivity of the latter. Further, expression and alternative splicing of multiple genes involved in cell survival, cell motility, and synapse formation are affected following Hnrnpu’s conditional truncation. Finally, we identified pharmaceutical and genetic agents that can partially reverse the loss of cortical structures in Hnrnpu mutated embryonic brains, ameliorate radial neuronal migration defects and rescue cultured neural progenitors’ cell death., HNRNPU is an RNA splicing protein associated with brain disorders such as early onset seizures. Here they show that HNRNPU functions to maintain neural progenitors and their progeny by regulating splicing of key neuronal genes.},
pmcid = {PMC9304408}
}
@article{sardoneAntisenseOligonucleotideBasedTherapy2017,
title = {Antisense {{Oligonucleotide-Based Therapy}} for {{Neuromuscular Disease}}},
author = {Sardone, Valentina and Zhou, Haiyan and Muntoni, Francesco and Ferlini, Alessandra and Falzarano, Maria Sofia},
date = {2017-04-05},
journaltitle = {Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry},
shortjournal = {Molecules},
volume = {22},
number = {4},
eprint = {28379182},
eprinttype = {pmid},
pages = {563},
issn = {1420-3049},
doi = {10.3390/molecules22040563},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6154734/},
urldate = {2021-11-30},
abstract = {Neuromuscular disorders such as Duchenne Muscular Dystrophy and Spinal Muscular Atrophy are neurodegenerative genetic diseases characterized primarily by muscle weakness and wasting. Until recently there were no effective therapies for these conditions, but antisense oligonucleotides, a new class of synthetic single stranded molecules of nucleic acids, have demonstrated promising experimental results and are at different stages of regulatory approval. The antisense oligonucleotides can modulate the protein expression via targeting hnRNAs or mRNAs and inducing interference with splicing, mRNA degradation, or arrest of translation, finally, resulting in rescue or reduction of the target protein expression. Different classes of antisense oligonucleotides are being tested in several clinical trials, and limitations of their clinical efficacy and toxicity have been reported for some of these compounds, while more encouraging results have supported the development of others. New generation antisense oligonucleotides are also being tested in preclinical models together with specific delivery systems that could allow some of the limitations of current antisense oligonucleotides to be overcome, to improve the cell penetration, to achieve more robust target engagement, and hopefully also be associated with acceptable toxicity. This review article describes the chemical properties and molecular mechanisms of action of the antisense oligonucleotides and the therapeutic implications these compounds have in neuromuscular diseases. Current strategies and carrier systems available for the oligonucleotides delivery will be also described to provide an overview on the past, present and future of these appealing molecules.},
pmcid = {PMC6154734}
}
@article{sarkozyMutationalLandscapeGray2021,
title = {Mutational Landscape of Gray Zone Lymphoma},
author = {Sarkozy, Clémentine and Hung, Stacy S. and Chavez, Elizabeth A. and Duns, Gerben and Takata, Katsuyoshi and Chong, Lauren C. and Aoki, Tomohiro and Jiang, Aixiang and Miyata-Takata, Tomoko and Telenius, Adèle and Slack, Graham W. and Molina, Thierry Jo and Ben-Neriah, Susana and Farinha, Pedro and Dartigues, Peggy and Damotte, Diane and Mottok, Anja and Salles, Gilles A. and Casasnovas, Rene-Olivier and Savage, Kerry J. and Laurent, Camille and Scott, David W. and Traverse-Glehen, Alexandra and Steidl, Christian},
date = {2021-04-01},
journaltitle = {Blood},
shortjournal = {Blood},
volume = {137},
number = {13},
eprint = {32961552},
eprinttype = {pmid},
pages = {1765--1776},
issn = {1528-0020},
doi = {10.1182/blood.2020007507},
abstract = {The mutational landscape of gray zone lymphoma (GZL) has not yet been established, and differences from related entities are largely unknown. Here, we studied coding sequence mutations of 50 Epstein-Barr virus (EBV)-negative GZLs and 20 polymorphic EBV+ diffuse large B-cell lymphoma (DLBCL) not otherwise specified (poly-EBV-L) in comparison with classical Hodgkin lymphoma (cHL), primary mediastinal large B-cell lymphoma (PMBCL), and DLBCL. Exomes of 21 GZL and 7 poly-EBV-L cases, along with paired constitutional DNA, were analyzed as a discovery cohort, followed by targeted sequencing of 217 genes in an extension cohort of 29 GZL and 13 poly-EBV-L cases. GZL cases with thymic niche involvement (anterior mediastinal mass) exhibited a mutation profile closely resembling cHL and PMBCL, with SOCS1 (45\%), B2M (45\%), TNFAIP3 (35\%), GNA13 (35\%), LRRN3 (32\%), and NFKBIA (29\%) being the most recurrently mutated genes. In contrast, GZL cases without thymic niche involvement (n = 18) had a significantly distinct pattern that was enriched in mutations related to apoptosis defects (TP53 [39\%], BCL2 [28\%], BIRC6 [22\%]) and depleted in GNA13, XPO1, or NF-κB signaling pathway mutations (TNFAIP3, NFKBIE, IKBKB, NFKBIA). They also exhibited more BCL2/BCL6 rearrangements compared with thymic GZL. Poly-EBV-L cases presented a distinct mutational profile, including STAT3 mutations and a significantly lower coding mutation load in comparison with EBV- GZL. Our study highlights characteristic mutational patterns in GZL associated with presentation in the thymic niche, suggesting a common cell of origin and disease evolution overlapping with related anterior mediastinal lymphomas.},
langid = {english},
keywords = {Adolescent,Adult,Aged,Aged 80 and over,Epstein-Barr Virus Infections,Female,Hodgkin Disease,Humans,Lymphoma Large B-Cell Diffuse,Male,Mediastinal Neoplasms,Middle Aged,Mutation,Thymus Gland,Young Adult}
}
@article{satijaSpatialReconstructionSinglecell2015,
title = {Spatial Reconstruction of Single-Cell Gene Expression Data},
author = {Satija, Rahul and Farrell, Jeffrey A. and Gennert, David and Schier, Alexander F. and Regev, Aviv},
date = {2015-05},
journaltitle = {Nature Biotechnology},
shortjournal = {Nat Biotechnol},
volume = {33},
number = {5},
pages = {495--502},
publisher = {Nature Publishing Group},
issn = {1546-1696},
doi = {10.1038/nbt.3192},
url = {https://www.nature.com/articles/nbt.3192},
urldate = {2022-02-01},
abstract = {RNA-seq data from single cells are mapped to their location in complex tissues using gene expression atlases based on in situ hybridization.},
issue = {5},
langid = {english},
keywords = {Gastrulation,Machine learning,Statistical methods}
}
@article{satouPrognosticImpactMUM12017,
title = {Prognostic {{Impact}} of {{MUM1}}/{{IRF4 Expression}} in {{Burkitt Lymphoma}} ({{BL}}): {{A Reappraisal}} of 88 {{BL Patients}} in {{Japan}}},
shorttitle = {Prognostic {{Impact}} of {{MUM1}}/{{IRF4 Expression}} in {{Burkitt Lymphoma}} ({{BL}})},
author = {Satou, Akira and Asano, Naoko and Kato, Seiichi and Elsayed, Ahmed A. and Nakamura, Naoya and Miyoshi, Hiroaki and Ohshima, Koichi and Nakamura, Shigeo},
date = {2017-03},
journaltitle = {The American Journal of Surgical Pathology},
shortjournal = {Am J Surg Pathol},
volume = {41},
number = {3},
eprint = {28079574},
eprinttype = {pmid},
pages = {389--395},
issn = {1532-0979},
doi = {10.1097/PAS.0000000000000804},
abstract = {MUM1/IRF4 expression is detected in 18\% to 41\% of Burkitt lymphoma (BL). However, only a few studies of MUM1-positive (MUM1) BL have been reported, and its characteristics still remain controversial. To highlight the features of MUM1 BL, we compared the clinicopathologic characteristics of 37 cases of MUM1 and 51 cases of MUM1-negative (MUM1) BL in Japan. Compared with MUM1 BL, patients with MUM1 BL showed significantly younger onset (P=0.0062) and a higher ratio of females (P=0.013). We have also revealed the difference in the involved sites. The MUM1 group showed lower incidences of involvement of stomach (P=0.012) and tonsil (P=0.069). There was a more tendency in MUM1 group to involve colon (P=0.072), breast (P=0.073), and kidney (P=0.073). Regarding the prognosis, a trend toward a lower overall survival for MUM1 group was noted (P=0.089). Notably, comparing MUM1 and MUM1 BL cases of adults (age16 y old and above), the former showed significantly worse prognosis (P=0.041). Among the BL patients treated with the intensive chemotherapy, a standard therapy for BL, MUM1 cases showed worse prognosis (P=0.056). In conclusion, MUM1 BL showed worse prognosis, particularly in adult cases, compared with MUM1 BL. In addition, the difference of the onset age, sex ratio, and involved sites between the 2 groups was noted. Our results demonstrate that MUM1 expression might predict worse prognosis of BL, and MUM1 BL should be distinguished from MUM1 BL.},
langid = {english},
keywords = {Adolescent,Adult,Aged,Aged 80 and over,Biomarkers Tumor,Burkitt Lymphoma,Child,Child Preschool,Female,Follow-Up Studies,Humans,Immunohistochemistry,In Situ Hybridization Fluorescence,Interferon Regulatory Factors,Japan,Male,Middle Aged,Prognosis,Retrospective Studies,Survival Analysis,Young Adult}
}
@article{satpathyMassivelyParallelSinglecell2019,
title = {Massively Parallel Single-Cell Chromatin Landscapes of Human Immune Cell Development and Intratumoral {{T}} Cell Exhaustion},
author = {Satpathy, Ansuman T. and Granja, Jeffrey M. and Yost, Kathryn E. and Qi, Yanyan and Meschi, Francesca and McDermott, Geoffrey P. and Olsen, Brett N. and Mumbach, Maxwell R. and Pierce, Sarah E. and Corces, M. Ryan and Shah, Preyas and Bell, Jason C. and Jhutty, Darisha and Nemec, Corey M. and Wang, Jean and Wang, Li and Yin, Yifeng and Giresi, Paul G. and Chang, Anne Lynn S. and Zheng, Grace X. Y. and Greenleaf, William J. and Chang, Howard Y.},
date = {2019-08},
journaltitle = {Nature Biotechnology},
shortjournal = {Nat Biotechnol},
volume = {37},
number = {8},
eprint = {31375813},
eprinttype = {pmid},
pages = {925--936},
issn = {1546-1696},
doi = {10.1038/s41587-019-0206-z},
abstract = {Understanding complex tissues requires single-cell deconstruction of gene regulation with precision and scale. Here, we assess the performance of a massively parallel droplet-based method for mapping transposase-accessible chromatin in single cells using sequencing (scATAC-seq). We apply scATAC-seq to obtain chromatin profiles of more than 200,000 single cells in human blood and basal cell carcinoma. In blood, application of scATAC-seq enables marker-free identification of cell type-specific cis- and trans-regulatory elements, mapping of disease-associated enhancer activity and reconstruction of trajectories of cellular differentiation. In basal cell carcinoma, application of scATAC-seq reveals regulatory networks in malignant, stromal and immune cells in the tumor microenvironment. Analysis of scATAC-seq profiles from serial tumor biopsies before and after programmed cell death protein 1 blockade identifies chromatin regulators of therapy-responsive T cell subsets and reveals a shared regulatory program that governs intratumoral CD8+ T cell exhaustion and CD4+ T follicular helper cell development. We anticipate that scATAC-seq will enable the unbiased discovery of gene regulatory factors across diverse biological systems.},
langid = {english},
pmcid = {PMC7299161},
keywords = {Bone Marrow Cells,Cell Line,Chromatin,Computer Simulation,Gene Expression Regulation,Hematopoiesis,High-Throughput Nucleotide Sequencing,Humans,Leukocytes Mononuclear,Single-Cell Analysis,T-Lymphocytes,Transcription Factors}
}
@article{saundersStrelkaAccurateSomatic2012,
title = {Strelka: Accurate Somatic Small-Variant Calling from Sequenced Tumor-Normal Sample Pairs},
shorttitle = {Strelka},
author = {Saunders, Christopher T. and Wong, Wendy S. W. and Swamy, Sajani and Becq, Jennifer and Murray, Lisa J. and Cheetham, R. Keira},
date = {2012-07-15},
journaltitle = {Bioinformatics (Oxford, England)},
shortjournal = {Bioinformatics},
volume = {28},
number = {14},
eprint = {22581179},
eprinttype = {pmid},
pages = {1811--1817},
issn = {1367-4811},
doi = {10.1093/bioinformatics/bts271},
abstract = {MOTIVATION: Whole genome and exome sequencing of matched tumor-normal sample pairs is becoming routine in cancer research. The consequent increased demand for somatic variant analysis of paired samples requires methods specialized to model this problem so as to sensitively call variants at any practical level of tumor impurity. RESULTS: We describe Strelka, a method for somatic SNV and small indel detection from sequencing data of matched tumor-normal samples. The method uses a novel Bayesian approach which represents continuous allele frequencies for both tumor and normal samples, while leveraging the expected genotype structure of the normal. This is achieved by representing the normal sample as a mixture of germline variation with noise, and representing the tumor sample as a mixture of the normal sample with somatic variation. A natural consequence of the model structure is that sensitivity can be maintained at high tumor impurity without requiring purity estimates. We demonstrate that the method has superior accuracy and sensitivity on impure samples compared with approaches based on either diploid genotype likelihoods or general allele-frequency tests. AVAILABILITY: The Strelka workflow source code is available at ftp://strelka@ftp.illumina.com/. CONTACT: csaunders@illumina.com},
langid = {english},
keywords = {Bayes Theorem,Computational Biology,Exome,Gene Frequency,Genetic Variation,Genome,Humans,INDEL Mutation,Models Genetic,Neoplasms,Sequence Alignment}
}
@article{savageMolecularSignatureMediastinal2003,
title = {The Molecular Signature of Mediastinal Large {{B-cell}} Lymphoma Differs from That of Other Diffuse Large {{B-cell}} Lymphomas and Shares Features with Classical {{Hodgkin}} Lymphoma.},
author = {Savage, Kerry J and Monti, Stefano and Kutok, Jeffery L and Cattoretti, Giorgio and Neuberg, Donna and family=Leval, given=Laurence, prefix=de, useprefix=true and Kurtin, Paul and Dal Cin, Paola and Ladd, Christine and Feuerhake, Friedrich and Aguiar, Ricardo C T and Li, Sigui and Salles, Gilles and Berger, Francoise and Jing, Wen and Pinkus, Geraldine S and Habermann, Thomas and Dalla-Favera, Riccardo and Harris, Nancy Lee and Aster, Jon C and Golub, Todd R and Shipp, Margaret A},
date = {2003-12},
journaltitle = {Blood},
volume = {102},
number = {12},
pages = {3871--3879}
}
@article{schapiroHistoCATAnalysisCell2017,
title = {{{histoCAT}}: Analysis of Cell Phenotypes and Interactions in Multiplex Image Cytometry Data},
shorttitle = {{{histoCAT}}},
author = {Schapiro, Denis and Jackson, Hartland W. and Raghuraman, Swetha and Fischer, Jana R. and Zanotelli, Vito R. T. and Schulz, Daniel and Giesen, Charlotte and Catena, Raúl and Varga, Zsuzsanna and Bodenmiller, Bernd},
date = {2017-09},
journaltitle = {Nature Methods},
shortjournal = {Nat Methods},
volume = {14},
number = {9},
pages = {873--876},
publisher = {Nature Publishing Group},
issn = {1548-7105},
doi = {10.1038/nmeth.4391},
url = {https://www.nature.com/articles/nmeth.4391},
urldate = {2022-02-03},
abstract = {The histology topography cytometry analysis toolbox (histoCAT) enables quantitative analysis and exploration of highly multiplexed imaging data for better understanding of individual cells in the context of tissue architecture.},
issue = {9},
langid = {english},
keywords = {Imaging,Software}
}
@article{schererDistinctBiologicalSubtypes2016,
title = {Distinct Biological Subtypes and Patterns of Genome Evolution in Lymphoma Revealed by Circulating Tumor {{DNA}}.},
author = {Scherer, Florian and Kurtz, David M and Newman, Aaron M and Stehr, Henning and Craig, Alexander F M and Esfahani, Mohammad Shahrokh and Lovejoy, Alexander F and Chabon, Jacob J and Klass, Daniel M and Liu, Chih Long and Zhou, Li and Glover, Cynthia and Visser, Brendan C and Poultsides, George A and Advani, Ranjana H and Maeda, Lauren S and Gupta, Neel K and Levy, Ronald and Ohgami, Robert S and Kunder, Christian A and Diehn, Maximilian and Alizadeh, Ash A},
date = {2016-11},
journaltitle = {Science translational medicine},
volume = {8},
number = {364},
pages = {364ra155}
}
@article{schifSOCS1MutationSubtypes,
title = {{{SOCS1 Mutation Subtypes Predict Divergent Outcomes}} in {{Diffuse Large B-Cell Lymphoma}} ({{DLBCL}}) {{Patients}}.},
author = {Schif, Birgit and Lennerz, Jochen K and Kohler, Christian W and Bentink, Stefan and Kreuz, Markus and Melzner, Ingo and Ritz, Olga and Trümper, Lorenz and Loeffler, Markus and Spang, Rainer and Möller, Peter},
journaltitle = {Oncotarget}
}
@article{schmidlinNewInsightsRegulation2009,
title = {New Insights into the Regulation of Human {{B-cell}} Differentiation},
author = {Schmidlin, Heike and Diehl, Sean A. and Blom, Bianca},
date = {2009-06-01},
journaltitle = {Trends in Immunology},
shortjournal = {Trends in Immunology},
volume = {30},
number = {6},
pages = {277--285},
issn = {1471-4906},
doi = {10.1016/j.it.2009.03.008},
url = {https://www.sciencedirect.com/science/article/pii/S1471490609000787},
urldate = {2022-10-06},
abstract = {B lymphocytes provide the cellular basis of the humoral immune response. All stages of this process, from B-cell activation to formation of germinal centers and differentiation into memory B cells or plasma cells, are influenced by extrinsic signals and controlled by transcriptional regulation. Compared to naïve B cells, memory B cells display a distinct expression profile, which allows for their rapid secondary responses. Indisputably, many B-cell malignancies result from aberrations in the circuitry controlling B-cell function, particularly during the germinal centre (GC) reaction. Here, we review new insights into memory B-cell subtypes, recent literature on transcription factors regulating human B-cell differentiation and further evidence for B-cell lymphomagenesis emanating from errors during GC cell reactions.},
langid = {english}
}
@article{schmidtCirculatingTumorDNA,
title = {Circulating Tumor {{DNA}} Reflects Therapy Response in Colorectal Cancer},
author = {Schmidt, Kerstin and Diehl, Frank and Choti, Michael and Romans, Kathy and Kinzler, Kenneth and Diaz, Luis and Vogelstein, Bert},
journaltitle = {AACR Meeting Abstracts},
volume = {2008},
pages = {40},
issue = {3\_Molecular\_Diagnostics\_Meeting}
}
@article{schmitzBurkittLymphomaPathogenesis2012,
title = {Burkitt Lymphoma Pathogenesis and Therapeutic Targets from Structural and Functional Genomics},
author = {Schmitz, Roland and Young, Ryan M. and Ceribelli, Michele and Jhavar, Sameer and Xiao, Wenming and Zhang, Meili and Wright, George and Shaffer, Arthur L. and Hodson, Daniel J. and Buras, Eric and Liu, Xuelu and Powell, John and Yang, Yandan and Xu, Weihong and Zhao, Hong and Kohlhammer, Holger and Rosenwald, Andreas and Kluin, Philip and Müller-Hermelink, Hans Konrad and Ott, German and Gascoyne, Randy D. and Connors, Joseph M. and Rimsza, Lisa M. and Campo, Elias and Jaffe, Elaine S. and Delabie, Jan and Smeland, Erlend B. and Ogwang, Martin D. and Reynolds, Steven J. and Fisher, Richard I. and Braziel, Rita M. and Tubbs, Raymond R. and Cook, James R. and Weisenburger, Dennis D. and Chan, Wing C. and Pittaluga, Stefania and Wilson, Wyndham and Waldmann, Thomas A. and Rowe, Martin and Mbulaiteye, Sam M. and Rickinson, Alan B. and Staudt, Louis M.},
date = {2012-10-04},
journaltitle = {Nature},
shortjournal = {Nature},
volume = {490},
number = {7418},
eprint = {22885699},
eprinttype = {pmid},
pages = {116--120},
issn = {1476-4687},
doi = {10.1038/nature11378},
abstract = {Burkitt's lymphoma (BL) can often be cured by intensive chemotherapy, but the toxicity of such therapy precludes its use in the elderly and in patients with endemic BL in developing countries, necessitating new strategies. The normal germinal centre B cell is the presumed cell of origin for both BL and diffuse large B-cell lymphoma (DLBCL), yet gene expression analysis suggests that these malignancies may use different oncogenic pathways. BL is subdivided into a sporadic subtype that is diagnosed in developed countries, the Epstein-Barr-virus-associated endemic subtype, and an HIV-associated subtype, but it is unclear whether these subtypes use similar or divergent oncogenic mechanisms. Here we used high-throughput RNA sequencing and RNA interference screening to discover essential regulatory pathways in BL that cooperate with MYC, the defining oncogene of this cancer. In 70\% of sporadic BL cases, mutations affecting the transcription factor TCF3 (E2A) or its negative regulator ID3 fostered TCF3 dependency. TCF3 activated the pro-survival phosphatidylinositol-3-OH kinase pathway in BL, in part by augmenting tonic B-cell receptor signalling. In 38\% of sporadic BL cases, oncogenic CCND3 mutations produced highly stable cyclin D3 isoforms that drive cell cycle progression. These findings suggest opportunities to improve therapy for patients with BL.},
langid = {english},
pmcid = {PMC3609867},
keywords = {Basic Helix-Loop-Helix Transcription Factors,Burkitt Lymphoma,Cell Cycle,Cyclin D3,Cyclin-Dependent Kinase 6,Genes myc,Genomics,High-Throughput Nucleotide Sequencing,Humans,Inhibitor of Differentiation Proteins,Molecular Targeted Therapy,Neoplasm Proteins,Phosphatidylinositol 3-Kinases,Receptors Antigen B-Cell,RNA Interference,Signal Transduction}
}
@article{schmitzGeneticsPathogenesisDiffuse2018,
title = {Genetics and {{Pathogenesis}} of {{Diffuse Large B-Cell Lymphoma}}},
author = {Schmitz, Roland and Wright, George W. and Huang, Da Wei and Johnson, Calvin A. and Phelan, James D. and Wang, James Q. and Roulland, Sandrine and Kasbekar, Monica and Young, Ryan M. and Shaffer, Arthur L. and Hodson, Daniel J. and Xiao, Wenming and Yu, Xin and Yang, Yandan and Zhao, Hong and Xu, Weihong and Liu, Xuelu and Zhou, Bin and Du, Wei and Chan, Wing C. and Jaffe, Elaine S. and Gascoyne, Randy D. and Connors, Joseph M. and Campo, Elias and Lopez-Guillermo, Armando and Rosenwald, Andreas and Ott, German and Delabie, Jan and Rimsza, Lisa M. and Tay Kuang Wei, Kevin and Zelenetz, Andrew D. and Leonard, John P. and Bartlett, Nancy L. and Tran, Bao and Shetty, Jyoti and Zhao, Yongmei and Soppet, Dan R. and Pittaluga, Stefania and Wilson, Wyndham H. and Staudt, Louis M.},
date = {2018-04-12},
journaltitle = {The New England Journal of Medicine},
shortjournal = {N Engl J Med},
volume = {378},
number = {15},
eprint = {29641966},
eprinttype = {pmid},
pages = {1396--1407},
issn = {1533-4406},
doi = {10.1056/NEJMoa1801445},
abstract = {BACKGROUND: Diffuse large B-cell lymphomas (DLBCLs) are phenotypically and genetically heterogeneous. Gene-expression profiling has identified subgroups of DLBCL (activated B-cell-like [ABC], germinal-center B-cell-like [GCB], and unclassified) according to cell of origin that are associated with a differential response to chemotherapy and targeted agents. We sought to extend these findings by identifying genetic subtypes of DLBCL based on shared genomic abnormalities and to uncover therapeutic vulnerabilities based on tumor genetics. METHODS: We studied 574 DLBCL biopsy samples using exome and transcriptome sequencing, array-based DNA copy-number analysis, and targeted amplicon resequencing of 372 genes to identify genes with recurrent aberrations. We developed and implemented an algorithm to discover genetic subtypes based on the co-occurrence of genetic alterations. RESULTS: We identified four prominent genetic subtypes in DLBCL, termed MCD (based on the co-occurrence of MYD88L265P and CD79B mutations), BN2 (based on BCL6 fusions and NOTCH2 mutations), N1 (based on NOTCH1 mutations), and EZB (based on EZH2 mutations and BCL2 translocations). Genetic aberrations in multiple genes distinguished each genetic subtype from other DLBCLs. These subtypes differed phenotypically, as judged by differences in gene-expression signatures and responses to immunochemotherapy, with favorable survival in the BN2 and EZB subtypes and inferior outcomes in the MCD and N1 subtypes. Analysis of genetic pathways suggested that MCD and BN2 DLBCLs rely on "chronic active" B-cell receptor signaling that is amenable to therapeutic inhibition. CONCLUSIONS: We uncovered genetic subtypes of DLBCL with distinct genotypic, epigenetic, and clinical characteristics, providing a potential nosology for precision-medicine strategies in DLBCL. (Funded by the Intramural Research Program of the National Institutes of Health and others.).},
langid = {english},
pmcid = {PMC6010183},
keywords = {Antineoplastic Combined Chemotherapy Protocols,Biopsy,Epigenesis Genetic,Exome,Gene Expression Profiling,Genetic Heterogeneity,Genotype,Humans,Kaplan-Meier Estimate,Lymphoma Large B-Cell Diffuse,Mutation,Prognosis,Sequence Analysis DNA,Transcriptome}
}
@article{schmitzTNFAIP3A20Tumor2009,
title = {{{TNFAIP3}} ({{A20}}) Is a Tumor Suppressor Gene in {{Hodgkin}} Lymphoma and Primary Mediastinal {{B}} Cell Lymphoma},
author = {Schmitz, Roland and Hansmann, Martin-Leo and Bohle, Verena and Martin-Subero, Jose Ignacio and Hartmann, Sylvia and Mechtersheimer, Gunhild and Klapper, Wolfram and Vater, Inga and Giefing, Maciej and Gesk, Stefan and Stanelle, Jens and Siebert, Reiner and Küppers, Ralf},
date = {2009-05-11},
journaltitle = {The Journal of Experimental Medicine},
shortjournal = {J Exp Med},
volume = {206},
number = {5},
eprint = {19380639},
eprinttype = {pmid},
pages = {981--989},
issn = {1540-9538},
doi = {10.1084/jem.20090528},
abstract = {Proliferation and survival of Hodgkin and Reed/Sternberg (HRS) cells, the malignant cells of classical Hodgkin lymphoma (cHL), are dependent on constitutive activation of nuclear factor kappaB (NF-kappaB). NF-kappaB activation through various stimuli is negatively regulated by the zinc finger protein A20. To determine whether A20 contributes to the pathogenesis of cHL, we sequenced TNFAIP3, encoding A20, in HL cell lines and laser-microdissected HRS cells from cHL biopsies. We detected somatic mutations in 16 out of 36 cHLs (44\%), including missense mutations in 2 out of 16 Epstein-Barr virus-positive (EBV(+)) cHLs and a missense mutation, nonsense mutations, and frameshift-causing insertions or deletions in 14 out of 20 EBV(-) cHLs. In most mutated cases, both TNFAIP3 alleles were inactivated, including frequent chromosomal deletions of TNFAIP3. Reconstitution of wild-type TNFAIP3 in A20-deficient cHL cell lines revealed a significant decrease in transcripts of selected NF-kappaB target genes and caused cytotoxicity. Extending the mutation analysis to primary mediastinal B cell lymphoma (PMBL), another lymphoma with constitutive NF-kappaB activity, revealed destructive mutations in 5 out of 14 PMBLs (36\%). This report identifies TNFAIP3 (A20), a key regulator of NF-kappaB activity, as a novel tumor suppressor gene in cHL and PMBL. The significantly higher frequency of TNFAIP3 mutations in EBV(-) than EBV(+) cHL suggests complementing functions of TNFAIP3 inactivation and EBV infection in cHL pathogenesis.},
langid = {english},
pmcid = {PMC2715030},
keywords = {Cell Line Tumor,Chromosome Deletion,DNA Transposable Elements,DNA-Binding Proteins,Epstein-Barr Virus Infections,Frameshift Mutation,Genes Tumor Suppressor,Hodgkin Disease,Humans,Intracellular Signaling Peptides and Proteins,Lymphoma B-Cell,Mutation,Mutation Missense,Nuclear Proteins,Polymorphism Single Nucleotide,Transcription Genetic,Tumor Necrosis Factor alpha-Induced Protein 3}
}
@article{schneiderAlterationsCD58Gene2015,
title = {Alterations of the {{CD58}} Gene in Classical {{Hodgkin}} Lymphoma},
author = {Schneider, Markus and Schneider, Stefanie and Zühlke-Jenisch, Reina and Klapper, Wolfram and Sundström, Christer and Hartmann, Sylvia and Hansmann, Martin-Leo and Siebert, Reiner and Küppers, Ralf and Giefing, Maciej},
date = {2015-10},
journaltitle = {Genes, Chromosomes \& Cancer},
shortjournal = {Genes Chromosomes Cancer},
volume = {54},
number = {10},
eprint = {26194173},
eprinttype = {pmid},
pages = {638--645},
issn = {1098-2264},
doi = {10.1002/gcc.22276},
abstract = {Immune evasion plays a central role in the pathophysiology of classical Hodgkin lymphoma (cHL). As mutations of the CD58 gene contribute to immune evasion of diffuse large B cell lymphoma tumor cells, we studied whether alterations of the CD58 gene also occur in Hodgkin and Reed/Sternberg (HRS) cells of cHL. Single nucleotide polymorphism chip analysis revealed homozygous deletions within the CD58 gene in two cHL cell lines (SUP-HD1 and U-HO1). Sequencing of the CD58 gene in seven cHL cell lines disclosed in addition a homozygous splice site mutation in cell line KM-H2. None of the three mutated lines expressed CD58 protein on their surface. Thus, three of seven cHL cell lines analyzed harbor destructive CD58 mutations. Molecular analysis of isolated HRS cells from 10 primary cases of cHL; however, did not reveal any case with a CD58 mutation. A FICTION study indicated heterozygous deletions of CD58 in 3 of 13 cHL analyzed. Overall, we report frequent inactivating mutations of CD58 in cHL cell lines, but their rare occurrence in primary HRS cells. As the three cHL cell lines with CD58 mutations were all established from HRS cells located in pleural effusions, i.e., outside the normal lymph node microenvironment, in end-stages of the disease, CD58 inactivation in cHL might be predominantly prevalent to such situations.},
langid = {english},
keywords = {CD58 Antigens,Cell Line Tumor,Cells Cultured,Hodgkin Disease,Humans,Mutation,Tumor Escape}
}
@article{schollMutationsRegionFAS2007,
title = {Mutations within the 5' Region of {{FAS}}/{{CD95}} Gene in Nodal Diffuse Large {{B-cell}} Lymphoma},
author = {Scholl, Vanesa and Stefanoff, Claudio Gustavo and Hassan, Rocio and Spector, Nelson and Renault, Ilana Zalcberg},
date = {2007-05},
journaltitle = {Leukemia \& Lymphoma},
shortjournal = {Leuk Lymphoma},
volume = {48},
number = {5},
eprint = {17487740},
eprinttype = {pmid},
pages = {957--963},
issn = {1042-8194},
doi = {10.1080/10428190701230858},
abstract = {CD95 is a cell-surface receptor that mediates apoptosis. A possible association between CD95 mutations and extranodal diffuse large B-cell lymphomas (DLBCL) has been reported. To further elucidate this question, a mutation analysis within the 5' region and exon 9 of CD95 was performed in a series of 66 DLBCL patients, by polymerase chain reaction, single-strand conformational polymorphism, and sequencing in all cases. Four mutations, all within the 5' region, were detected in three cases of primary nodal DLBCL (6.3\% of primary DLBCL), probably originated as by-products of the somatic hypermutation process. No CD95 mutations in the two analyzed regions were detected in primary extranodal DLBCL, mediastinal large B-cell lymphoma (MLBCL), and DLBCL arising from indolent low-grade lymphomas. Because of our results, a review of published data with respect to the site of mutations was performed, which suggested a different distribution of mutations in nodal and extranodal DLBCL.},
langid = {english},
keywords = {Apoptosis,Base Sequence,Disease Progression,DNA Mutational Analysis,fas Receptor,Gene Expression Regulation Neoplastic,Humans,Lymphatic Metastasis,Lymphoma B-Cell,Lymphoma Large B-Cell Diffuse,Models Genetic,Molecular Sequence Data,Mutation,Polymerase Chain Reaction,Polymorphism Single-Stranded Conformational}
}
@article{scolesAntisenseOligonucleotidesPrimer2019,
title = {Antisense Oligonucleotides: {{A}} Primer},
shorttitle = {Antisense Oligonucleotides},
author = {Scoles, Daniel R. and Minikel, Eric V. and Pulst, Stefan M.},
date = {2019-04-01},
journaltitle = {Neurology Genetics},
volume = {5},
number = {2},
publisher = {Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology},
issn = {2376-7839},
doi = {10.1212/NXG.0000000000000323},
url = {https://ng.neurology.org/content/5/2/e323},
urldate = {2022-10-05},
abstract = {There are few disease-modifying therapeutics for neurodegenerative diseases, but successes on the development of antisense oligonucleotide (ASO) therapeutics for spinal muscular atrophy and Duchenne muscular dystrophy predict a robust future for ASOs in medicine. Indeed, existing pipelines for the development of ASO therapies for spinocerebellar ataxias, Huntington disease, Alzheimer disease, amyotrophic lateral sclerosis, Parkinson disease, and others, and increased focus by the pharmaceutical industry on ASO development, strengthen the outlook for using ASOs for neurodegenerative diseases. Perhaps the most significant advantage to ASO therapeutics over other small molecule approaches is that acquisition of the target sequence provides immediate knowledge of putative complementary oligonucleotide therapeutics. In this review, we describe the various types of ASOs, how they are used therapeutically, and the present efforts to develop new ASO therapies that will contribute to a forthcoming toolkit for treating multiple neurodegenerative diseases.},
langid = {english}
}
@article{scottDeterminingCelloforiginSubtypes2014,
title = {Determining Cell-of-Origin Subtypes of Diffuse Large {{B-cell}} Lymphoma Using Gene Expression in Formalin-Fixed Paraffin-Embedded Tissue.},
author = {Scott, David W and Wright, George W and Williams, P Mickey and Lih, Chih-Jian and Walsh, William and Jaffe, Elaine S and Rosenwald, Andreas and Campo, Elias and Chan, Wing C and Connors, Joseph M and Smeland, Erlend B and Mottok, Anja and Braziel, Rita M and Ott, German and Delabie, Jan and Tubbs, Raymond R and Cook, James R and Weisenburger, Dennis D and Greiner, Timothy C and Glinsmann-Gibson, Betty J and Fu, Kai and Staudt, Louis M and Gascoyne, Randy D and Rimsza, Lisa M},
date = {2014-02},
journaltitle = {Blood},
volume = {123},
number = {8},
pages = {1214--1217}
}
@article{scottHighgradeBcellLymphoma2018,
title = {High-Grade {{B-cell}} Lymphoma with {{MYC}} and {{BCL2}} and/or {{BCL6}} Rearrangements with Diffuse Large {{B-cell}} Lymphoma Morphology},
author = {Scott, David W. and King, Rebecca L. and Staiger, Annette M. and Ben-Neriah, Susana and Jiang, Aixiang and Horn, Heike and Mottok, Anja and Farinha, Pedro and Slack, Graham W. and Ennishi, Daisuke and Schmitz, Norbert and Pfreundschuh, Michael and Nowakowski, Grzegorz S. and Kahl, Brad S. and Connors, Joseph M. and Gascoyne, Randy D. and Ott, German and Macon, William R. and Rosenwald, Andreas},
date = {2018-05-03},
journaltitle = {Blood},
volume = {131},
number = {18},
eprint = {29475959},
eprinttype = {pmid},
pages = {2060--2064},
issn = {0006-4971, 1528-0020},
doi = {10.1182/blood-2017-12-820605},
url = {http://www.bloodjournal.org/content/131/18/2060},
urldate = {2019-07-08},
abstract = {Visual Abstract {$<$}img class="highwire-fragment fragment-image" alt="Figure1" src="http://www.bloodjournal.org/content/bloodjournal/131/18/2060/F1.medium.gif" width="440" height="394"/{$>$}Download figureOpen in new tabDownload powerpoint High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (HGBL-DH/TH) is a newly defined entity in the latest World Health Organization Classification. Accurate diagnosis would appear to mandate fluorescence in situ hybridization (FISH) for all tumors with diffuse large B-cell lymphoma (DLBCL) morphology. We present the results of FISH, cell-of-origin, and immunohistochemistry (IHC) testing from 1228 DLBCL biopsies from 3 clinical trials and a population-based registry. HGBL-DH/TH made up 7.9\% of the DLBCL, confined primarily to the germinal center B-cell–like (GCB; 13.3\%) compared with activated B-cell-like (ABC; 1.7\%) subtype (P {$<$} .001). HGBL-DH/TH with BCL2 rearrangement is a GCB phenomenon with no cases observed in 415 ABC DLBCL. A screening strategy restricting FISH testing to tumors of GCB subtype (by Lymph2Cx or Hans IHC) plus dual protein expression of MYC and BCL2 by IHC could limit testing to 11\% to 14\% of tumors, with a positive predictive value of 30\% to 37\%; however, this strategy would miss approximately one-quarter of tumors with HBGL-DH/TH with BCL2 rearrangement and one-third of all HGBL-DH/TH. These results provide accurate estimation of the proportion of HGBL-DH/TH among tumors with DLBCL morphology and allow determination of the impact of various methods available to screen DLBCL tumors for FISH testing.},
langid = {english}
}
@article{scottNewMolecularAssay2017,
title = {New {{Molecular Assay}} for the {{Proliferation Signature}} in {{Mantle Cell Lymphoma Applicable}} to {{Formalin-Fixed Paraffin-Embedded Biopsies}}},
author = {Scott, David W. and Abrisqueta, Pau and Wright, George W. and Slack, Graham W. and Mottok, Anja and Villa, Diego and Jares, Pedro and Rauert-Wunderlich, Hilka and Royo, Cristina and Clot, Guillem and Pinyol, Magda and Boyle, Merrill and Chan, Fong Chun and Braziel, Rita M. and Chan, Wing C. and Weisenburger, Dennis D. and Cook, James R. and Greiner, Timothy C. and Fu, Kai and Ott, German and Delabie, Jan and Smeland, Erlend B. and Holte, Harald and Jaffe, Elaine S. and Steidl, Christian and Connors, Joseph M. and Gascoyne, Randy D. and Rosenwald, Andreas and Staudt, Louis M. and Campo, Elias and Rimsza, Lisa M.},
date = {2017-03-14},
journaltitle = {Journal of Clinical Oncology},
shortjournal = {JCO},
volume = {35},
number = {15},
pages = {1668--1677},
issn = {0732-183X},
doi = {10.1200/JCO.2016.70.7901},
url = {https://ascopubs.org/doi/full/10.1200/JCO.2016.70.7901},
urldate = {2019-12-21},
abstract = {PurposeMantle cell lymphoma is an aggressive B-cell neoplasm that displays heterogeneous outcomes after treatment. In 2003, the Lymphoma/Leukemia Molecular Profiling Project described a powerful biomarker—the proliferation signature—using gene expression in fresh frozen material. Herein, we describe the training and validation of a new assay that measures the proliferation signature in RNA derived from routinely available formalin-fixed paraffin-embedded (FFPE) biopsies.MethodsForty-seven FFPE biopsies were used to train an assay on the NanoString platform, using microarray gene expression data of matched fresh frozen biopsies as a gold standard. The locked assay was applied to pretreatment FFPE lymph node biopsies from an independent cohort of 110 patients uniformly treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. Seventeen biopsies were tested across three laboratories to assess assay reproducibility.ResultsThe MCL35 assay, which contained a 17-gene proliferation signature, yielded gene expression of sufficient quality to assign an assay score and risk group in 108 (98\%) of 110 archival FFPE biopsies. The MCL35 assay assigned patients to high-risk (26\%), standard-risk (29\%), and low-risk (45\%) groups, with different lengths of overall survival (OS): a median of 1.1, 2.6, and 8.6 years, respectively (log-rank for trend, P {$<$} .001). In multivariable analysis, these risk groups and the Mantle Cell Lymphoma International Prognostic Index were independently associated with OS (P {$<$} .001 for both variables). Concordance of risk assignment across the three independent laboratories was 100\%.ConclusionThe newly developed and validated MCL35 assay for FFPE biopsies uses the proliferation signature to define groups of patients with significantly different OS independent of the Mantle Cell Lymphoma International Prognostic Index. Importantly, the analytic and clinical validity of this assay defines it as a reliable biomarker to support risk-adapted clinical trials.}
}
@article{scruccaMclustClusteringClassification2016,
title = {Mclust 5: {{Clustering}}, {{Classification}} and {{Density Estimation Using Gaussian Finite Mixture Models}}},
shorttitle = {Mclust 5},
author = {Scrucca, Luca and Fop, Michael and Murphy, T. Brendan and Raftery, Adrian E.},
date = {2016-08},
journaltitle = {The R Journal},
shortjournal = {R J},
volume = {8},
number = {1},
eprint = {27818791},
eprinttype = {pmid},
pages = {289--317},
issn = {2073-4859},
abstract = {Finite mixture models are being used increasingly to model a wide variety of random phenomena for clustering, classification and density estimation. mclust is a powerful and popular package which allows modelling of data as a Gaussian finite mixture with different covariance structures and different numbers of mixture components, for a variety of purposes of analysis. Recently, version 5 of the package has been made available on CRAN. This updated version adds new covariance structures, dimension reduction capabilities for visualisation, model selection criteria, initialisation strategies for the EM algorithm, and bootstrap-based inference, making it a full-featured R package for data analysis via finite mixture modelling.},
langid = {english},
pmcid = {PMC5096736}
}
@article{sedlazeckAccurateDetectionComplex2018,
title = {Accurate Detection of Complex Structural Variations Using Single Molecule Sequencing},
author = {Sedlazeck, Fritz J. and Rescheneder, Philipp and Smolka, Moritz and Fang, Han and Nattestad, Maria and family=Haeseler, given=Arndt, prefix=von, useprefix=true and Schatz, Michael C.},
date = {2018-06},
journaltitle = {Nature methods},
shortjournal = {Nat Methods},
volume = {15},
number = {6},
eprint = {29713083},
eprinttype = {pmid},
pages = {461--468},
issn = {1548-7091},
doi = {10.1038/s41592-018-0001-7},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5990442/},
urldate = {2022-02-07},
abstract = {Structural variations (SVs) are the largest source of genetic variation, but remain poorly understood because of limited genomics technology. Single molecule long-read sequencing from Pacific Biosciences and Oxford Nanopore has the potential to dramatically advance the field, although their high error rates challenge existing methods. Addressing this need, we introduce open-source methods for long-read alignment (NGMLR, https://github.com/philres/ngmlr) and SV identification (Sniffles, https://github.com/fritzsedlazeck/Sniffles) that enable unprecedented SV sensitivity and precision, including within repeat-rich regions and of complex nested events that can have significant impact on human disorders. Examining several datasets, including healthy and cancerous human genomes, we discover thousands of novel variants using long-reads and categorize systematic errors in short-read approaches. NGMLR and Sniffles are further able to automatically filter false events and operate on low amounts of coverage to address the cost factor that has hindered the application of long-reads in clinical and research settings.},
pmcid = {PMC5990442}
}
@article{sehnRevisedInternationalPrognostic,
title = {The Revised {{International Prognostic Index}} ({{R-IPI}}) Is a Better Predictor of Outcome than the Standard {{IPI}} for Patients with Diffuse Large {{B-cell}} Lymphoma Treated with {{R-CHOP}}.},
author = {Sehn, Laurie H and Berry, Brian and Chhanabhai, Mukesh and Fitzgerald, Catherine and Gill, Karamjit and Hoskins, Paul and Klasa, Richard and Savage, Kerry J and Shenkier, Tamara and Sutherland, Judy and Gascoyne, Randy D and Connors, Joseph M},
journaltitle = {Blood},
volume = {109},
number = {5},
pages = {1857--1861}
}
@article{seifertOriginPathogenesisCell2013,
title = {Origin and Pathogenesis of {{B}} Cell Lymphomas.},
author = {Seifert, M. and Scholtysik, R. and Küppers, R.},
date = {2013},
journaltitle = {Methods in molecular biology},
volume = {971},
pages = {1--25}
}
@article{shaMolecularHighGradeBCell2018,
title = {Molecular {{High-Grade B-Cell Lymphoma}}: {{Defining}} a {{Poor-Risk Group That Requires Different Approaches}} to {{Therapy}}},
shorttitle = {Molecular {{High-Grade B-Cell Lymphoma}}},
author = {Sha, Chulin and Barrans, Sharon and Cucco, Francesco and Bentley, Michael A. and Care, Matthew A. and Cummin, Thomas and Kennedy, Hannah and Thompson, Joe S. and Uddin, Rahman and Worrillow, Lisa and Chalkley, Rebecca and family=Hoppe, given=Moniek, prefix=van, useprefix=true and Ahmed, Sophia and Maishman, Tom and Caddy, Josh and Schuh, Anna and Mamot, Christoph and Burton, Catherine and Tooze, Reuben and Davies, Andrew and Du, Ming-Qing and Johnson, Peter W.M. and Westhead, David R.},
date = {2018-12-03},
journaltitle = {Journal of Clinical Oncology},
shortjournal = {J Clin Oncol},
volume = {37},
number = {3},
pages = {202--212},
issn = {0732-183X},
doi = {10.1200/JCO.18.01314},
url = {https://ascopubs.org/doi/full/10.1200/JCO.18.01314},
urldate = {2019-07-08},
abstract = {PurposeBiologic heterogeneity is a feature of diffuse large B-cell lymphoma (DLBCL), and the existence of a subgroup with poor prognosis and phenotypic proximity to Burkitt lymphoma is well known. Conventional cytogenetics identifies some patients with rearrangements of MYC and BCL2 and/or BCL6 (double-hit lymphomas) who are increasingly treated with more intensive chemotherapy, but a more biologically coherent and clinically useful definition of this group is required.Patients and MethodsWe defined a molecular high-grade (MHG) group by applying a gene expression–based classifier to 928 patients with DLBCL from a clinical trial that investigated the addition of bortezomib to standard rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. The prognostic significance of MHG was compared with existing biomarkers. We performed targeted sequencing of 70 genes in 400 patients and explored molecular pathology using gene expression signature databases. Findings were validated in an independent data set.ResultsThe MHG group comprised 83 patients (9\%), with 75 in the cell-of-origin germinal center B-cell-like group. MYC rearranged and double-hit groups were strongly over-represented in MHG but comprised only one half of the total. Gene expression analysis revealed a proliferative phenotype with a relationship to centroblasts. Progression-free survival rate at 36 months after R-CHOP in the MHG group was 37\% (95\% CI, 24\% to 55\%) compared with 72\% (95\% CI, 68\% to 77\%) for others, and an analysis of treatment effects suggested a possible positive effect of bortezomib. Double-hit lymphomas lacking the MHG signature showed no evidence of worse outcome than other germinal center B-cell-like cases.ConclusionMHG defines a biologically coherent high-grade B-cell lymphoma group with distinct molecular features and clinical outcomes that effectively doubles the size of the poor-prognosis, double-hit group. Patients with MHG may benefit from intensified chemotherapy or novel targeted therapies.}
}
@article{shannonGeneticStructureVillage2015,
title = {Genetic Structure in Village Dogs Reveals a {{Central Asian}} Domestication Origin},
author = {Shannon, Laura M. and Boyko, Ryan H. and Castelhano, Marta and Corey, Elizabeth and Hayward, Jessica J. and McLean, Corin and White, Michelle E. and Said, Mounir Abi and Anita, Baddley A. and Bondjengo, Nono Ikombe and Calero, Jorge and Galov, Ana and Hedimbi, Marius and Imam, Bulu and Khalap, Rajashree and Lally, Douglas and Masta, Andrew and Oliveira, Kyle C. and Pérez, Lucía and Randall, Julia and Tam, Nguyen Minh and Trujillo-Cornejo, Francisco J. and Valeriano, Carlos and Sutter, Nathan B. and Todhunter, Rory J. and Bustamante, Carlos D. and Boyko, Adam R.},
date = {2015-11-03},
journaltitle = {Proceedings of the National Academy of Sciences},
shortjournal = {PNAS},
volume = {112},
number = {44},
eprint = {26483491},
eprinttype = {pmid},
pages = {13639--13644},
issn = {0027-8424, 1091-6490},
doi = {10.1073/pnas.1516215112},
url = {http://www.pnas.org/content/112/44/13639},
urldate = {2018-10-29},
abstract = {Dogs were the first domesticated species, originating at least 15,000 y ago from Eurasian gray wolves. Dogs today consist primarily of two specialized groups—a diverse set of nearly 400 pure breeds and a far more populous group of free-ranging animals adapted to a human commensal lifestyle (village dogs). Village dogs are more genetically diverse and geographically widespread than purebred dogs making them vital for unraveling dog population history. Using a semicustom 185,805-marker genotyping array, we conducted a large-scale survey of autosomal, mitochondrial, and Y chromosome diversity in 4,676 purebred dogs from 161 breeds and 549 village dogs from 38 countries. Geographic structure shows both isolation and gene flow have shaped genetic diversity in village dog populations. Some populations (notably those in the Neotropics and the South Pacific) are almost completely derived from European stock, whereas others are clearly admixed between indigenous and European dogs. Importantly, many populations—including those of Vietnam, India, and Egypt—show minimal evidence of European admixture. These populations exhibit a clear gradient of short-range linkage disequilibrium consistent with a Central Asian domestication origin.},
langid = {english},
keywords = {admixture,domestication,haplotype diversity,introgression,linkage disequilibrium}
}
@article{shatkinEndsAffairCapping2000,
title = {The Ends of the Affair: {{Capping}} and Polyadenylation},
shorttitle = {The Ends of the Affair},
author = {Shatkin, Aaron J. and Manley, James L.},
date = {2000-10},
journaltitle = {Nature Structural Biology},
shortjournal = {Nat Struct Mol Biol},
volume = {7},
number = {10},
pages = {838--842},
publisher = {Nature Publishing Group},
issn = {1545-9985},
doi = {10.1038/79583},
url = {https://www.nature.com/articles/nsb1000_838},
urldate = {2022-10-06},
abstract = {Nearly all mRNAs are post-transcriptionally modified at their 5′ and 3′ ends, by capping and polyadenylation, respectively. These essential modifications are of course chemically quite distinct, as are the enzymatic complexes responsible for their synthesis. But recent studies have uncovered some similarities as well. For example, both involve entirely protein machinery, which is now the exception rather than the rule in RNA processing and modification reactions, and the two reactions share one important factor, namely RNA polymerase II. In this brief review, we describe progress in understanding the enzymes and factors that participate in these two processes, highlighting the evolutionary conservation, from yeast to humans, that has become apparent.},
issue = {10},
langid = {english},
keywords = {Biochemistry,Biological Microscopy,general,Life Sciences,Membrane Biology,Protein Structure}
}
@article{shaTransferringGenomicsClinic2015,
title = {Transferring Genomics to the Clinic: Distinguishing {{Burkitt}} and Diffuse Large {{B}} Cell Lymphomas},
shorttitle = {Transferring Genomics to the Clinic},
author = {Sha, Chulin and Barrans, Sharon and Care, Matthew A. and Cunningham, David and Tooze, Reuben M. and Jack, Andrew and Westhead, David R.},
date = {2015-07-01},
journaltitle = {Genome Medicine},
shortjournal = {Genome Med},
volume = {7},
number = {1},
eprint = {26207141},
eprinttype = {pmid},
issn = {1756-994X},
doi = {10.1186/s13073-015-0187-6},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4512160/},
urldate = {2020-02-05},
abstract = {Background Classifiers based on molecular criteria such as gene expression signatures have been developed to distinguish Burkitt lymphoma and diffuse large B cell lymphoma, which help to explore the intermediate cases where traditional diagnosis is difficult. Transfer of these research classifiers into a clinical setting is challenging because there are competing classifiers in the literature based on different methodology and gene sets with no clear best choice; classifiers based on one expression measurement platform may not transfer effectively to another; and, classifiers developed using fresh frozen samples may not work effectively with the commonly used and more convenient formalin fixed paraffin-embedded samples used in routine diagnosis. Methods Here we thoroughly compared two published high profile classifiers developed on data from different Affymetrix array platforms and fresh-frozen tissue, examining their transferability and concordance. Based on this analysis, a new Burkitt and diffuse large B cell lymphoma classifier (BDC) was developed and employed on Illumina DASL data from our own paraffin-embedded samples, allowing comparison with the diagnosis made in a central haematopathology laboratory and evaluation of clinical relevance. Results We show that both previous classifiers can be recapitulated using very much smaller gene sets than originally employed, and that the classification result is closely dependent on the Burkitt lymphoma criteria applied in the training set. The BDC classification on our data exhibits high agreement (\textasciitilde 95 \%) with the original diagnosis. A simple outcome comparison in the patients presenting intermediate features on conventional criteria suggests that the cases classified as Burkitt lymphoma by BDC have worse response to standard diffuse large B cell lymphoma treatment than those classified as diffuse large B cell lymphoma. Conclusions In this study, we comprehensively investigate two previous Burkitt lymphoma molecular classifiers, and implement a new gene expression classifier, BDC, that works effectively on paraffin-embedded samples and provides useful information for treatment decisions. The classifier is available as a free software package under the GNU public licence within the R statistical software environment through the link http://www.bioinformatics.leeds.ac.uk/labpages/softwares/ or on github https://github.com/Sharlene/BDC. Electronic supplementary material The online version of this article (doi:10.1186/s13073-015-0187-6) contains supplementary material, which is available to authorized users.},
pmcid = {PMC4512160}
}
@article{shenBCL2ProteinExpression2004,
title = {{{BCL2}} Protein Expression Parallels Its {{mRNA}} Level in Normal and Malignant {{B}} Cells},
author = {Shen, Yulei and Iqbal, Javeed and Huang, James Z. and Zhou, Guimei and Chan, Wing C.},
date = {2004-11-01},
journaltitle = {Blood},
shortjournal = {Blood},
volume = {104},
number = {9},
pages = {2936--2939},
issn = {0006-4971},
doi = {10.1182/blood-2004-01-0243},
url = {https://doi.org/10.1182/blood-2004-01-0243},
urldate = {2022-10-06},
abstract = {The regulation of B-cell lymphoma 2 (BCL2) protein expression in germinal center (GC) B cells has been controversial. Previous reports have indicated posttranscriptional regulation plays a dominant role. However, a number of recent studies contradicted these reports. Using real-time polymerase chain reaction (PCR) and Standardized Reverse Transcriptase-PCR (StaRT-PCR), we measured the level of mRNA expression in GC, mantle zone (MNZ), and marginal zone (MGZ) cells from laser capture microdissection. Both quantitative RT-PCR measurements of microdissected GC cells from tonsils showed that GC cells had low expression of BCL2 transcripts commensurate with the low protein expression level. These results are in agreement with microarray studies on fluorescence-activated cell sorter (FACS)-sorted cells and microdissected GC cells. We also examined BCL2 mRNA and protein expression on a series of 30 cases of diffuse large B-cell lymphoma (DLBCL) and found, in general, a good correlation. The results suggested that BCL2 protein expression is regulated at the transcriptional level in normal B cells and in the neoplastic cells in most B-cell lymphoproliferative disorders.}
}
@article{shenSensitiveTumourDetection2018,
title = {Sensitive Tumour Detection and Classification Using Plasma Cell-Free {{DNA}} Methylomes},
author = {Shen, Shu Yi and Singhania, Rajat and Fehringer, Gordon and Chakravarthy, Ankur and Roehrl, Michael H. A. and Chadwick, Dianne and Zuzarte, Philip C. and Borgida, Ayelet and Wang, Ting Ting and Li, Tiantian and Kis, Olena and Zhao, Zhen and Spreafico, Anna and Medina, Tiago da Silva and Wang, Yadon and Roulois, David and Ettayebi, Ilias and Chen, Zhuo and Chow, Signy and Murphy, Tracy and Arruda, Andrea and O'Kane, Grainne M. and Liu, Jessica and Mansour, Mark and McPherson, John D. and O'Brien, Catherine and Leighl, Natasha and Bedard, Philippe L. and Fleshner, Neil and Liu, Geoffrey and Minden, Mark D. and Gallinger, Steven and Goldenberg, Anna and Pugh, Trevor J. and Hoffman, Michael M. and Bratman, Scott V. and Hung, Rayjean J. and De Carvalho, Daniel D.},
date = {2018-11},
journaltitle = {Nature},
shortjournal = {Nature},
volume = {563},
number = {7732},
eprint = {30429608},
eprinttype = {pmid},
pages = {579--583},
issn = {1476-4687},
doi = {10.1038/s41586-018-0703-0},
abstract = {The use of liquid biopsies for cancer detection and management is rapidly gaining prominence1. Current methods for the detection of circulating tumour DNA involve sequencing somatic mutations using cell-free DNA, but the sensitivity of these methods may be low among patients with early-stage cancer given the limited number of recurrent mutations2-5. By contrast, large-scale epigenetic alterations-which are tissue- and cancer-type specific-are not similarly constrained6 and therefore potentially have greater ability to detect and classify cancers in patients with early-stage disease. Here we develop a sensitive, immunoprecipitation-based protocol to analyse the methylome of small quantities of circulating cell-free DNA, and demonstrate the ability to detect large-scale DNA methylation changes that are enriched for tumour-specific patterns. We also demonstrate robust performance in cancer detection and classification across an extensive collection of plasma samples from several tumour types. This work sets the stage to establish biomarkers for the minimally invasive detection, interception and classification of early-stage cancers based on plasma cell-free DNA methylation patterns.},
langid = {english},
keywords = {Adenocarcinoma,Animals,Biomarkers Tumor,Cell Line Tumor,Cell-Free Nucleic Acids,Colorectal Neoplasms,DNA Methylation,DNA Mutational Analysis,DNA Neoplasm,Early Detection of Cancer,Epigenesis Genetic,Female,Heterografts,Humans,Liquid Biopsy,Male,Mice,Mice Inbred NOD,Mice SCID,Neoplasm Transplantation,Neoplasms,Organ Specificity,Pancreatic Neoplasms}
}
@article{shenTATABindingProtein2000,
title = {The {{TATA}} Binding Protein, c-{{Myc}} and Survivin Genes Are Not Somatically Hypermutated, While {{Ig}} and {{BCL6}} Genes Are Hypermutated in Human Memory {{B}} Cells},
author = {Shen, Hong Ming and Michael, Nancy and Kim, Nayun and Storb, Ursula},
date = {2000-07-01},
journaltitle = {International Immunology},
shortjournal = {International Immunology},
volume = {12},
number = {7},
pages = {1085--1093},
issn = {0953-8178},
doi = {10.1093/intimm/12.7.1085},
url = {https://doi.org/10.1093/intimm/12.7.1085},
urldate = {2024-03-25},
abstract = {Immunoglobulin (Ig) genes are hypermutated in mature B cells after interaction with antigen and T cells in a germinal center reaction. We and others have recently shown that the human BCL6 gene is also hypermutated in human peripheral blood memory B cells and tonsils. A preliminary analysis of other non-Ig genes (c-Myc, S14 and AFP) suggested that they were not mutated in memory B cells. We have now performed an in-depth analysis of three non-Ig genes that are expressed in germinal center B cells in two human donors in whom BCL6 is highly mutated. It was found that the TATA binding protein (TBP), c-Myc and survivin genes are not hypermutated. This lack of targeting by the Ig hypermutation mechanism must be due to the lack of regulatory DNA elements, since the primary sequences of the three tested genes have at least as high intrinsic mutability indices as the BCL6 gene.}
}
@article{sherryDbSNPNCBIDatabase2001,
title = {{{dbSNP}}: The {{NCBI}} Database of Genetic Variation},
shorttitle = {{{dbSNP}}},
author = {Sherry, S. T. and Ward, M.-H. and Kholodov, M. and Baker, J. and Phan, L. and Smigielski, E. M. and Sirotkin, K.},
date = {2001-01-01},
journaltitle = {Nucleic Acids Research},
shortjournal = {Nucleic Acids Research},
volume = {29},
number = {1},
pages = {308--311},
issn = {0305-1048},
doi = {10.1093/nar/29.1.308},
url = {https://doi.org/10.1093/nar/29.1.308},
urldate = {2021-05-13},
abstract = {In response to a need for a general catalog of genome variation to address the large-scale sampling designs required by association studies, gene mapping and evolutionary biology, the National Center for Biotechnology Information (NCBI) has established the dbSNP database [S.T.Sherry, M.Ward and K.Sirotkin (1999) Genome Res., 9, 677–679]. Submissions to dbSNP will be integrated with other sources of information at NCBI such as GenBank, PubMed, LocusLink and the Human Genome Project data. The complete contents of dbSNP are available to the public at website: http://www.ncbi.nlm.nih.gov/SNP. The complete contents of dbSNP can also be downloaded in multiple formats via anonymous FTP at ftp://ncbi.nlm.nih.gov/snp/.}
}
@article{shiIL6inducedEnhancementCMyc2011,
title = {{{IL-6-induced Enhancement}} of c-{{Myc Translation}} in {{Multiple Myeloma Cells}}: {{CRITICAL ROLE OF CYTOPLASMIC LOCALIZATION OF THE RNA-BINDING PROTEIN hnRNP A1}} *},
shorttitle = {{{IL-6-induced Enhancement}} of c-{{Myc Translation}} in {{Multiple Myeloma Cells}}},
author = {Shi, Yijiang and Frost, Patrick and Hoang, Bao and Benavides, Angelica and Gera, Joseph and Lichtenstein, Alan},
date = {2011-01-07},
journaltitle = {Journal of Biological Chemistry},
shortjournal = {Journal of Biological Chemistry},
volume = {286},
number = {1},
eprint = {20974848},
eprinttype = {pmid},
pages = {67--78},
publisher = {Elsevier},
issn = {0021-9258, 1083-351X},
doi = {10.1074/jbc.M110.153221},
url = {https://www.jbc.org/article/S0021-9258(20)54197-5/abstract},
urldate = {2022-10-05},
abstract = {{$<$}p{$>$}Prior work indicates that IL-6 can stimulate c-Myc expression in multiple myeloma (MM) cells, which is independent of effects on transcription and due to enhanced translation mediated by an internal ribosome entry site in the 5′-UTR of the c-Myc RNA. The RNA-binding protein hnRNP A1 (A1) was also critical to IL-6-stimulated translation. Because A1 shuttles between nucleus and cytoplasm, we investigated whether the ability of IL-6 to enhance Myc translation was mediated by stimulation of A1 shuttling. In MM cell lines and primary specimens, IL-6 increased A1 cytoplasmic localization. In contrast, there was no effect on the total cellular levels of A1. Use of a dominant negative A1 construct, which prevents endogenous A1 from nucleus-to-cytoplasm transit, prevented the ability of IL-6 to enhance Myc internal ribosome entry site activity, Myc protein expression, and MM cell growth. IL-6-stimulated cytoplasmic localization was mediated by alterations in the C-terminal M9 peptide of A1, and this correlated with the ability of IL-6 to induce serine phosphorylation of this domain. A p38 kinase inhibitor prevented IL-6-induced A1 phosphorylation. Thus, IL-6 activates c-Myc translation in MM cells by inducing A1 phosphorylation and cytoplasmic localization in a p38-dependent fashion. These data suggest A1 as a potential therapeutic target in MM.{$<$}/p{$>$}},
langid = {english}
}
@article{shiIL6InducedStimulation2008,
title = {{{IL-6}}–{{Induced Stimulation}} of c-{{Myc Translation}} in {{Multiple Myeloma Cells Is Mediated}} by {{Myc Internal Ribosome Entry Site Function}} and the {{RNA-Binding Protein}}, {{hnRNP A1}}},
author = {Shi, Yijiang and Frost, Patrick J. and Hoang, Bao Q. and Benavides, Angelica and Sharma, Sanjai and Gera, Joseph F. and Lichtenstein, Alan K.},
date = {2008-12-15},
journaltitle = {Cancer Research},
shortjournal = {Cancer Research},
volume = {68},
number = {24},
pages = {10215--10222},
issn = {0008-5472},
doi = {10.1158/0008-5472.CAN-08-1066},
url = {https://doi.org/10.1158/0008-5472.CAN-08-1066},
urldate = {2022-10-05},
abstract = {Prior work indicates that c-myc translation is up-regulated in multiple myeloma cells. To test a role for interleukin (IL)-6 in myc translation, we studied the IL-6–responsive ANBL-6 and IL-6–autocrine U266 cell lines as well as primary patient samples. IL-6 increased c-myc translation, which was resistant to rapamycin, indicating a mechanism independent of mammalian target of rapamycin (mTOR) and cap-dependent translation. In contrast, the cytokine enhanced cap-independent translation via a stimulatory effect on the myc internal ribosome entry site (IRES). As known IRES-trans–activating factors (ITAF) were unaffected by IL-6, we used a yeast-three-hybrid screen to identify novel ITAFs and identified hnRNP A1 (A1) as a mediator of the IL-6 effect. A1 specifically interacted with the myc IRES in filter binding assays as well as EMSAs. Treatment of myeloma cells with IL-6 induced serine phosphorylation of A1 and increased its binding to the myc IRES in vivo in myeloma cells. Primary patient samples also showed binding between A1 and the IRES. RNA interference to knock down hnRNP A1 prevented an IL-6 increase in myc protein expression, myc IRES activity, and cell growth. These data point to hnRNP A1 as a critical regulator of c-myc translation and a potential therapeutic target in multiple myeloma. [Cancer Res 2008;68(24):10215–22]}
}
@article{shinBRAFV600EMAP2K12015,
title = {{{BRAF V600E}} and {{MAP2K1}} Mutations in Hairy Cell Leukemia and Splenic Marginal Zone Lymphoma Cases},
author = {Shin, Sang-Yong and Lee, Seung-Tae and Kim, Hee-Jin and Ki, Chang-Seok and Jung, Chul Won and Kim, Jong-Won and Kim, Sun-Hee},
date = {2015-03},
journaltitle = {Annals of Laboratory Medicine},
shortjournal = {Ann Lab Med},
volume = {35},
number = {2},
eprint = {25729732},
eprinttype = {pmid},
pages = {257--259},
issn = {2234-3814},
doi = {10.3343/alm.2015.35.2.257},
langid = {english},
pmcid = {PMC4330180},
keywords = {Adult,Aged,Antineoplastic Combined Chemotherapy Protocols,Cyclophosphamide,Doxorubicin,Female,Humans,Immunoglobulin Variable Region,Leukemia Hairy Cell,Lymphoma Non-Hodgkin,Male,MAP Kinase Kinase 1,Middle Aged,Mutation,Polymorphism Single Nucleotide,Prednisone,Pregnancy,Proto-Oncogene Proteins B-raf,Real-Time Polymerase Chain Reaction,Vincristine}
}
@article{shiPCBP1DepletionPromotes2018,
title = {{{PCBP1}} Depletion Promotes Tumorigenesis through Attenuation of {{p27Kip1 mRNA}} Stability and Translation},
author = {Shi, Hongshun and Li, Hui and Yuan, Ronghua and Guan, Wen and Zhang, Xiaomei and Zhang, Shaoyang and Zhang, Wenliang and Tong, Fang and Li, Li and Song, Zhihong and Wang, Changwei and Yang, Shulan and Wang, Haihe},
date = {2018-08-07},
journaltitle = {Journal of experimental \& clinical cancer research: CR},
shortjournal = {J Exp Clin Cancer Res},
volume = {37},
number = {1},
eprint = {30086790},
eprinttype = {pmid},
pages = {187},
issn = {1756-9966},
doi = {10.1186/s13046-018-0840-1},
abstract = {BACKGROUND: Poly C Binding Protein 1 (PCBP1) is an RNA-binding protein that binds and regulates translational activity of subsets of cellular mRNAs. Depletion of PCBP1 is implicated in various carcinomas, but the underlying mechanism in tumorigenesis remains elusive. METHODS: We performed a transcriptome-wide screen to identify novel bounding mRNA of PCBP1. The bind regions between PCBP1 with target mRNA were investigated by using point mutation and luciferase assay. Cell proliferation, cell cycle, tumorigenesis and cell apoptosis were also evaluated in ovary and colon cancer cell lines. The mechanism that PCBP1 affects p27 was analyzed by mRNA stability and ribosome profiling assays. We analyzed PCBP1 and p27 expression in ovary, colon and renal tumor samples and adjacent non-tumor tissues using RT-PCR, Western Blotting and immunohistochemistry. The prognostic significance of PCBP1 and p27 also analyzed using online databases. RESULTS: We identified cell cycle inhibitor p27Kip1 (p27) as a novel PCBP1-bound transcript. We then demonstrated that binding of PCBP1 to p27 3'UTR via its KH1 domain mainly stabilizes p27 mRNA, while enhances its translation to fuel p27 expression, prior to p27 protein degradation. The upregulated p27 consequently inhibits cell proliferation, cell cycle progression and tumorigenesis, whereas promotes cell apoptosis under paclitaxel treatment. Conversely, knockdown of PCBP1 in turn compromises p27 mRNA stability, leading to lower p27 level and tumorigenesis in vivo. Moreover, forced depletion of p27 counteracts the tumor suppressive ability of PCBP1 in the same PCBP1 over-expressing cells. Physiologically, we showed that decreases of both p27 mRNA and its protein expressions are well correlated to PCBP1 depletion in ovary, colon and renal tumor samples, independent of the p27 ubiquitin ligase Skp2 level. Correlation of PCBP1 with p27 is also found in the tamoxifen, doxorubincin and lapatinib resistant breast cancer cells of GEO database. CONCLUSION: Our results thereby indicate that loss of PCBP1 expression firstly attenuates p27 expression at post-transcriptional level, and subsequently promotes carcinogenesis. PCBP1 could be used as a diagnostic marker to cancer patients.},
langid = {english},
pmcid = {PMC6081911},
keywords = {3' Untranslated Regions,Animals,Apoptosis,Breast Neoplasms,Carcinogenesis,Cell Cycle,Cell Line Tumor,Cyclin-Dependent Kinase Inhibitor p27,DNA-Binding Proteins,Female,Heterogeneous-Nuclear Ribonucleoproteins,Heterografts,Humans,Mice,Mice Inbred BALB C,mRNA stability,Ovarian Neoplasms,p27,PCBP1,Phosphorylation,Protein Biosynthesis,RNA Messenger,RNA Stability,RNA-Binding Proteins,Up-Regulation}
}
@article{shlienCopyNumberVariations2009,
title = {Copy Number Variations and Cancer},
author = {Shlien, Adam and Malkin, David},
date = {2009-06-16},
journaltitle = {Genome Medicine},
shortjournal = {Genome Medicine},
volume = {1},
number = {6},
pages = {62},
issn = {1756-994X},
doi = {10.1186/gm62},
url = {https://doi.org/10.1186/gm62},
urldate = {2020-05-25},
abstract = {DNA copy number variations (CNVs) are an important component of genetic variation, affecting a greater fraction of the genome than single nucleotide polymorphisms (SNPs). The advent of high-resolution SNP arrays has made it possible to identify CNVs. Characterization of widespread constitutional (germline) CNVs has provided insight into their role in susceptibility to a wide spectrum of diseases, and somatic CNVs can be used to identify regions of the genome involved in disease phenotypes. The role of CNVs as risk factors for cancer is currently underappreciated. However, the genomic instability and structural dynamism that characterize cancer cells would seem to make this form of genetic variation particularly intriguing to study in cancer. Here, we provide a detailed overview of the current understanding of the CNVs that arise in the human genome and explore the emerging literature that reveals associations of both constitutional and somatic CNVs with a wide variety of human cancers.}
}
@article{shustikCorrelationsBCL6Rearrangement2010,
title = {Correlations between {{BCL6}} Rearrangement and Outcome in Patients with Diffuse Large {{B-cell}} Lymphoma Treated with {{CHOP}} or {{R-CHOP}}.},
author = {Shustik, Jesse and Han, Guangming and Farinha, Pedro and Johnson, Nathalie A and Ben-Neriah, Susana and Connors, Joseph M and Sehn, Laurie H and Horsman, Douglas E and Gascoyne, Randy D and Steidl, Christian},
date = {2010-01},
journaltitle = {Haematologica},
volume = {95},
number = {1},
pages = {96--101}
}
@article{simpsonDetectingDNACytosine2017,
title = {Detecting {{DNA}} Cytosine Methylation Using Nanopore Sequencing},
author = {Simpson, Jared T and Workman, Rachael E and family=Zuzarte, given=PC, given-i=PC and David, Matei and family=Dursi, given=LJ, given-i=LJ and Timp, Winston},
date = {2017},
journaltitle = {Nature Methods},
volume = {14},
number = {4},
eprint = {28218898},
eprinttype = {pmid},
pages = {407--410},
issn = {1548-7091},
doi = {10.1038/nmeth.4184},
url = {http://dx.doi.org/10.1038/nmeth.4184},
abstract = {In nanopore sequencing devices, electrolytic current signals are sensitive to base modifications, such as 5-methylcytosine (5-mC). Here we quantified the strength of this effect for the Oxford Nanopore Technologies MinION sequencer. By using synthetically methylated DNA, we were able to train a hidden Markov model to distinguish 5-mC from unmethylated cytosine. We applied our method to sequence the methylome of human DNA, without requiring special steps for library preparation.}
}
@article{sipahimalaniSystematicEvaluationAtaxia2007,
title = {A Systematic Evaluation of the Ataxia Telangiectasia Mutated Gene Does Not Show an Association with non‐{{Hodgkin}} Lymphoma},
author = {Sipahimalani, Payal and Spinelli, John J. and MacArthur, Amy C. and Lai, Agnes and Leach, Stephen R. and Janoo‐Gilani, Rozmin T. and Palmquist, Diana L. and Connors, Joseph M. and Gascoyne, Randy D. and Gallagher, Richard P. and Brooks‐Wilson, Angela R.},
date = {2007-07},
journaltitle = {International Journal of Cancer},
volume = {121},
number = {9},
eprint = {17640065},
eprinttype = {pmid},
pages = {1967--1975},
issn = {1097-0215},
doi = {10.1002/ijc.22888},
url = {http://dx.doi.org/10.1002/ijc.22888},
abstract = {The ataxia telangiectasia mutated (ATM) gene is critical for the detection and repair of DNA double-stranded breaks. Mutations in this gene cause the autosomal recessive syndrome ataxia telangiectasia (AT), an attribute of which is an increased risk of cancer, particularly lymphoma. We have undertaken a population-based case/control study to assess the influence of genetic variation in ATM on the risk of non-Hodgkin lymphoma (NHL). A number of the subtypes that constitute NHL have in common the occurrence of specific somatic translocations that contribute to lymphomagenesis. We hypothesize that ATM function is slightly attenuated by some variants, which could reduce double-stranded break repair capacity, contributing to the occurrence of translocations and subsequent lymphomas. We sequenced the promoter and all exons of ATM in the germline DNA of 86 NHL patients and identified 79 variants. Eighteen of these variants correspond to nonsynonymous amino acid differences, 6 of which were predicted to be deleterious to protein function; these variants were all rare. Eleven common variants make up 10 haplotypes that are specified by 7 tagSNPs. Linkage disequilibrium across the ATM gene is high but incomplete. TagSNPs and the 6 putatively deleterious variants were genotyped in 798 NHL cases and 793 controls. Our results indicate that common variants of ATM do not significantly contribute to the risk of NHL in the general population. However, some rare, functionally deleterious variants may contribute to an increased risk of development of rare subtypes of the disease. © 2007 Wiley-Liss, Inc.}
}
@article{skalniakMCPIP1ContributesToxicity2014,
title = {{{MCPIP1}} Contributes to the Toxicity of Proteasome Inhibitor {{MG-132}} in {{HeLa}} Cells by the Inhibition of {{NF-κB}}},
author = {Skalniak, Lukasz and Dziendziel, Monika and Jura, Jolanta},
date = {2014-07},
journaltitle = {Molecular and cellular biochemistry},
volume = {395},
number = {1-2},
pages = {253--263}
}
@article{skinniderBcl6Bcl2Protein,
title = {Bcl-6 and {{Bcl-2}} Protein Expression in Diffuse Large {{B-cell}} Lymphoma and Follicular Lymphoma: Correlation with 3q27 and 18q21 Chromosomal Abnormalities},
author = {Skinnider, B and Horsman, D and Dupuis, B and Gascoyne, R},
journaltitle = {Hum Pathol},
volume = {30},
number = {7},
pages = {803--808}
}
@article{smithDAZAP1RNAbindingProtein2011,
title = {{{DAZAP1}}, an {{RNA-binding}} Protein Required for Development and Spermatogenesis, Can Regulate {{mRNA}} Translation},
author = {Smith, Richard W. P. and Anderson, Ross C. and Smith, Joel W. S. and Brook, Matthew and Richardson, William A. and Gray, Nicola K.},
date = {2011-07},
journaltitle = {RNA (New York, N.Y.)},
shortjournal = {RNA},
volume = {17},
number = {7},
eprint = {21576381},
eprinttype = {pmid},
pages = {1282--1295},
issn = {1469-9001},
doi = {10.1261/rna.2717711},
abstract = {DAZ-associated protein 1 (DAZAP1) is an RNA-binding protein required for normal growth, development, and fertility in mice. However, its molecular functions have not been elucidated. Here we find that Xenopus laevis and human DAZAP1, which are each expressed as short and long forms, act as mRNA-specific activators of translation in a manner that is sensitive to the number of binding sites present within the 3' UTR. Domain mapping suggests that this conserved function is mainly associated with C-terminal regions of DAZAP1. Interestingly, we find that the expression of xDAZAP1 and its polysome association are developmentally controlled, the latter suggesting that the translational activator function of DAZAP1 is regulated. However, ERK phosphorylation of DAZAP1, which can alter protein interactions with its C terminus, does not play a role in regulating its ability to participate in translational complexes. Since relatively few mRNA-specific activators have been identified, we explored the mechanism by which DAZAP1 activates translation. By utilizing reporter mRNAs with internal ribosome entry sites, we establish that DAZAP1 stimulates translation initiation. Importantly, this activity is not dependent on the recognition of the 5' cap by initiation factors, showing that it functions downstream from this frequently regulated event, but is modulated by changes in the adenylation status of mRNAs. This suggests a function in the formation of "end-to-end" complexes, which are important for efficient initiation, which we show to be independent of a direct interaction with the bridging protein eIF4G.},
langid = {english},
pmcid = {PMC3138565},
keywords = {Amino Acid Sequence,Animals,Embryo Nonmammalian,Extracellular Signal-Regulated MAP Kinases,Gene Expression Regulation Developmental,Growth and Development,Humans,Male,Models Biological,Molecular Sequence Data,Oocytes,Phosphorylation,Protein Biosynthesis,RNA Messenger,RNA-Binding Proteins,Sequence Homology Amino Acid,Spermatogenesis,Xenopus laevis}
}
@article{smithPhosphodiesterasePDE4BLimits,
title = {The Phosphodiesterase {{PDE4B}} Limits {{cAMP-associated PI3K}}/{{AKT-dependent}} Apoptosis in Diffuse Large {{B-cell}} Lymphoma},
author = {Smith, P G},
journaltitle = {Blood},
volume = {105},
number = {1},
pages = {308--316}
}
@article{smithPrevalenceCharacterisationTRAF32020,
title = {The Prevalence and Characterisation of {{TRAF3}} and {{POT1}} Mutations in Canine {{B-cell}} Lymphoma},
author = {Smith, P. A. D. and Waugh, E. M. and Crichton, C. and Jarrett, R. F. and Morris, J. S.},
date = {2020-12-01},
journaltitle = {The Veterinary Journal},
shortjournal = {The Veterinary Journal},
volume = {266},
pages = {105575},
issn = {1090-0233},
doi = {10.1016/j.tvjl.2020.105575},
url = {https://www.sciencedirect.com/science/article/pii/S1090023320301520},
urldate = {2021-04-29},
abstract = {The genetic and mutational basis of canine lymphoma remains poorly understood. Several genes, including TRAF3 and POT1, are mutated in canine B-cell lymphoma (cBCL), and are likely involved in the pathogenesis of this disease. The purpose of this study was to assess the prevalence of TRAF3 and POT1 mutations in a cohort of dogs with cBCL, compared to dogs with non-cBCL diseases (including four dogs with T-cell lymphoma [cTCL]). Forty-nine dogs were included (n = 24 cBCL; n = 25 non-cBCL). Eleven dogs had matched non-tumour DNA assessed to determine if mutations were germline or somatic. All dogs had TRAF3 and POT1 assessed by Sanger sequencing. The prevalence of deleterious TRAF3 and POT1 mutations in cBCL was 36\% and 17\%, respectively. A deleterious TRAF3 mutation was suspected to be germline in 1/5 cases with matched non-tumour DNA available for comparison. Deleterious mutations were not found in specimens from the non-cBCL group. Several synonymous variants were identified in both genes in cBCL and non-cBCL samples, which likely represent polymorphisms. These results indicate TRAF3 and POT1 mutations are common in cBCL. Deleterious TRAF3 and POT1 mutations were only identified in dogs with cBCL, and not in dogs with non-cBCL diseases, suggesting they are important in the pathogenesis of cBCL. Future studies to investigate the prognostic and therapeutic implications of these mutations are required.},
langid = {english},
keywords = {Canine lymphoma,Genetics}
}
@article{soDiagnosticChallengesCase2013,
title = {Diagnostic Challenges in a Case of {{B}} Cell Lymphoma Unclassifiable with Features Intermediate between Diffuse Large {{B-cell}} Lymphoma and {{Burkitt}} Lymphoma.},
author = {So, Chi-Chiu and Yung, Ka-Hung and Chu, Man-Leng and Wan, Thomas S K},
date = {2013-10},
journaltitle = {International journal of hematology},
volume = {98},
number = {4},
pages = {478--482}
}
@inproceedings{soldiniNewlyDiscoveredMutations2013,
title = {The Newly Discovered Mutations in {{Burkitt}} ’ s Lymphoma May Constitute New Markers for Diagnosis , Prognosis and Predictive Value for Novel Therapeutic Targets ”},
author = {Soldini, D. and Campo, E.},
date = {2013}
}
@article{solinMultigeneExpressionAssay2013,
title = {A Multigene Expression Assay to Predict Local Recurrence Risk for Ductal Carcinoma in Situ of the Breast},
author = {Solin, Lawrence J. and Gray, Robert and Baehner, Frederick L. and Butler, Steven M. and Hughes, Lorie L. and Yoshizawa, Carl and Cherbavaz, Diana B. and Shak, Steven and Page, David L. and Sledge, George W. and Davidson, Nancy E. and Ingle, James N. and Perez, Edith A. and Wood, William C. and Sparano, Joseph A. and Badve, Sunil},
date = {2013-05-15},
journaltitle = {Journal of the National Cancer Institute},
shortjournal = {J. Natl. Cancer Inst.},
volume = {105},
number = {10},
eprint = {23641039},
eprinttype = {pmid},
pages = {701--710},
issn = {1460-2105},
doi = {10.1093/jnci/djt067},
abstract = {BACKGROUND: For women with ductal carcinoma in situ (DCIS) of the breast, the risk of developing an ipsilateral breast event (IBE; defined as local recurrence of DCIS or invasive carcinoma) after surgical excision without radiation is not well defined by clinical and pathologic characteristics. METHODS: The Oncotype DX breast cancer assay was performed for patients with DCIS treated with surgical excision without radiation in the Eastern Cooperative Oncology Group (ECOG) E5194 study. The association of the prospectively defined DCIS Score (calculated from seven cancer-related genes and five reference genes) with the risk of developing an IBE was analyzed using Cox regression. All statistical tests were two-sided. RESULTS: There were 327 patients with adequate tissue for analysis. The continuous DCIS Score was statistically significantly associated with the risk of developing an IBE (hazard ratio [HR] = 2.31, 95\% confidence interval [CI] = 1.15 to 4.49; P = .02) when adjusted for tamoxifen use (prespecified primary analysis) and with invasive IBE (unadjusted HR = 3.68, 95\% CI = 1.34 to 9.62; P = .01). For the prespecified DCIS risk groups of low, intermediate, and high, the 10-year risks of developing an IBE were 10.6\%, 26.7\%, and 25.9\%, respectively, and for an invasive IBE, 3.7\%, 12.3\%, and 19.2\%, respectively (both log rank P ≤ .006). In multivariable analyses, factors associated with IBE risk were DCIS Score, tumor size, and menopausal status (all P ≤ .02). CONCLUSIONS: The DCIS Score quantifies IBE risk and invasive IBE risk, complements traditional clinical and pathologic factors, and provides a new clinical tool to improve selecting individualized treatment for women with DCIS who meet the ECOG E5194 criteria.},
langid = {english},
pmcid = {PMC3653823},
keywords = {Adult,Aged,Biomarkers Tumor,Breast Neoplasms,Carcinoma Ductal Breast,Carcinoma Intraductal Noninfiltrating,Female,Gene Expression Profiling,Gene Expression Regulation Neoplastic,Humans,Kaplan-Meier Estimate,Mastectomy Segmental,Middle Aged,Neoplasm Grading,Neoplasm Recurrence Local,Neoplasm Staging,Predictive Value of Tests,Prognosis,Risk Assessment,Risk Factors}
}
@article{songBlimp1ProteinHans,
title = {Blimp-1 Protein and {{Hans}} Classification on Prognosis of Diffuse Large {{B-cell}} Lymphoma and Their Interrelation.},
author = {Song, Yan and Cao, Zhi and Li, Ling and Zhang, Hong-Tu and Zhang, Xun},
journaltitle = {Chinese journal of cancer},
volume = {29},
number = {9},
pages = {781--786}
}
@article{spinaGeneticsNodalMarginal2016,
title = {The Genetics of Nodal Marginal Zone Lymphoma},
author = {Spina, Valeria and Khiabanian, Hossein and Messina, Monica and Monti, Sara and Cascione, Luciano and Bruscaggin, Alessio and Spaccarotella, Elisa and Holmes, Antony B. and Arcaini, Luca and Lucioni, Marco and Tabbò, Fabrizio and Zairis, Sakellarios and Diop, Fary and Cerri, Michaela and Chiaretti, Sabina and Marasca, Roberto and Ponzoni, Maurilio and Deaglio, Silvia and Ramponi, Antonio and Tiacci, Enrico and Pasqualucci, Laura and Paulli, Marco and Falini, Brunangelo and Inghirami, Giorgio and Bertoni, Francesco and Foà, Robin and Rabadan, Raul and Gaidano, Gianluca and Rossi, Davide},
date = {2016-09-08},
journaltitle = {Blood},
shortjournal = {Blood},
volume = {128},
number = {10},
pages = {1362--1373},
issn = {0006-4971},
doi = {10.1182/blood-2016-02-696757},
pmcid = {PMC5016706},
abstract = {Nodal marginal zone lymphoma (NMZL) is a rare, indolent B-cell tumor that is distinguished from splenic marginal zone lymphoma (SMZL) by the different pattern of dissemination. NMZL still lacks distinct markers and remains orphan of specific cancer gene lesions. By combining whole-exome sequencing, targeted sequencing of tumor-related genes, whole-transcriptome sequencing, and high-resolution single nucleotide polymorphism array analysis, we aimed at disclosing the pathways that are molecularly deregulated in NMZL and we compare the molecular profile of NMZL with that of SMZL. These analyses identified a distinctive pattern of nonsilent somatic lesions in NMZL. In 35 NMZL patients, 41 genes were found recurrently affected in ≥3 (9\%) cases, including highly prevalent molecular lesions of MLL2 (also known as KMT2D; 34\%), PTPRD (20\%), NOTCH2 (20\%), and KLF2 (17\%). Mutations of PTPRD, a receptor-type protein tyrosine phosphatase regulating cell growth, were enriched in NMZL across mature B-cell tumors, functionally caused the loss of the phosphatase activity of PTPRD, and were associated with cell-cycle transcriptional program deregulation and increased proliferation index in NMZL. Although NMZL shared with SMZL a common mutation profile, NMZL harbored PTPRD lesions that were otherwise absent in SMZL. Collectively, these findings provide new insights into the genetics of NMZL, identify PTPRD lesions as a novel marker for this lymphoma across mature B-cell tumors, and support the distinction of NMZL as an independent clinicopathologic entity within the current lymphoma classification.}
}
@article{stansfeldUpdatedKielClassification1988,
title = {Updated {{Kiel}} Classification for Lymphomas},
author = {Stansfeld, A. G. and Diebold, J. and Noel, H. and Kapanci, Y. and Rilke, F. and Kelényi, G. and Sundstrom, C. and Lennert, K. and family=Unnik, given=J. A., prefix=van, useprefix=true and Mioduszewska, O.},
date = {1988-02-06},
journaltitle = {Lancet (London, England)},
shortjournal = {Lancet},
volume = {1},
number = {8580},
eprint = {2893097},
eprinttype = {pmid},
pages = {292--293},
issn = {0140-6736},
doi = {10.1016/s0140-6736(88)90367-4},
langid = {english},
keywords = {B-Lymphocytes,Humans,Lymphoma,Lymphoma Non-Hodgkin,T-Lymphocytes}
}
@article{steenLandscapeTumorCell2021,
title = {The Landscape of Tumor Cell States and Ecosystems in Diffuse Large {{B}} Cell Lymphoma},
author = {Steen, Chloé B. and Luca, Bogdan A. and Esfahani, Mohammad S. and Azizi, Armon and Sworder, Brian J. and Nabet, Barzin Y. and Kurtz, David M. and Liu, Chih Long and Khameneh, Farnaz and Advani, Ranjana H. and Natkunam, Yasodha and Myklebust, June H. and Diehn, Maximilian and Gentles, Andrew J. and Newman, Aaron M. and Alizadeh, Ash A.},
date = {2021-10-11},
journaltitle = {Cancer Cell},
shortjournal = {Cancer Cell},
volume = {39},
number = {10},
eprint = {34597589},
eprinttype = {pmid},
pages = {1422-1437.e10},
issn = {1878-3686},
doi = {10.1016/j.ccell.2021.08.011},
abstract = {Biological heterogeneity in diffuse large B cell lymphoma (DLBCL) is partly driven by cell-of-origin subtypes and associated genomic lesions, but also by diverse cell types and cell states in the tumor microenvironment (TME). However, dissecting these cell states and their clinical relevance at scale remains challenging. Here, we implemented EcoTyper, a machine-learning framework integrating transcriptome deconvolution and single-cell RNA sequencing, to characterize clinically relevant DLBCL cell states and ecosystems. Using this approach, we identified five cell states of malignant B cells that vary in prognostic associations and differentiation status. We also identified striking variation in cell states for 12 other lineages comprising the TME and forming cell state interactions in stereotyped ecosystems. While cell-of-origin subtypes have distinct TME composition, DLBCL ecosystems capture clinical heterogeneity within existing subtypes and extend beyond cell-of-origin and genotypic classes. These results resolve the DLBCL microenvironment at systems-level resolution and identify opportunities for therapeutic targeting (https://ecotyper.stanford.edu/lymphoma).},
langid = {english},
pmcid = {PMC9205168},
keywords = {CIBERSORTx,diffuse large B cell lymphoma,digital cytometry,DLBCL,Ecosystem,EcoTyper,expression deconvolution,Humans,lymphoma,Lymphoma Large B-Cell Diffuse,Prognosis,tumor ecosystems,tumor immunology,tumor microenvironment,Tumor Microenvironment}
}
@article{steenProfilingCellType2020,
title = {Profiling {{Cell Type Abundance}} and {{Expression}} in {{Bulk Tissues}} with {{CIBERSORTx}}},
author = {Steen, Chloé B. and Liu, Chih Long and Alizadeh, Ash A. and Newman, Aaron M.},
date = {2020},
journaltitle = {Methods in Molecular Biology (Clifton, N.J.)},
shortjournal = {Methods Mol Biol},
volume = {2117},
eprint = {31960376},
eprinttype = {pmid},
pages = {135--157},
issn = {1940-6029},
doi = {10.1007/978-1-0716-0301-7_7},
abstract = {CIBERSORTx is a suite of machine learning tools for the assessment of cellular abundance and cell type-specific gene expression patterns from bulk tissue transcriptome profiles. With this framework, single-cell or bulk-sorted RNA sequencing data can be used to learn molecular signatures of distinct cell types from a small collection of biospecimens. These signatures can then be repeatedly applied to characterize cellular heterogeneity from bulk tissue transcriptomes without physical cell isolation. In this chapter, we provide a detailed primer on CIBERSORTx and demonstrate its capabilities for high-throughput profiling of cell types and cellular states in normal and neoplastic tissues.},
langid = {english},
pmcid = {PMC7695353},
keywords = {Case-Control Studies,Cell Line Tumor,Cell Separation,Cellular heterogeneity,Computational Biology,Deconvolution,Digital cytometry,Gene expression,Gene Expression Profiling,Gene Expression Regulation Neoplastic,High-Throughput Nucleotide Sequencing,Humans,Machine Learning,Neoplasms,Organ Specificity,scRNA-seq,Single-Cell Analysis,Tumor microenvironment}
}
@article{steinhartPromisingPersonalizedTherapeutic,
title = {Promising Personalized Therapeutic Options for Diffuse Large {{B-cell}} Lymphoma Subtypes with Oncogene Addictions},
author = {Steinhart, J and Gartenhaus, R B},
journaltitle = {Clin Cancer Res}
}
@incollection{storeySAMThresholdingFalse2003,
title = {{{SAM Thresholding}} and {{False Discovery Rates}} for {{Detecting Differential Gene Expression}} in {{DNA Microarrays}}},
booktitle = {The {{Analysis}} of {{Gene Expression Data}}: {{Methods}} and {{Software}}},
author = {Storey, John D. and Tibshirani, Robert},
editor = {Parmigiani, Giovanni and Garrett, Elizabeth S. and Irizarry, Rafael A. and Zeger, Scott L.},
date = {2003},
series = {Statistics for {{Biology}} and {{Health}}},
pages = {272--290},
publisher = {Springer},
location = {New York, NY},
doi = {10.1007/0-387-21679-0_12},
url = {https://doi.org/10.1007/0-387-21679-0_12},
urldate = {2020-07-20},
abstract = {SAM is a computer package for correlating gene expression with an outcome parameter such as treatment, survival time, or diagnostic class. It thresholds an appropriate test statistic and reports the q-value of each test based on a set of sample permutations. SAM works as a Microsoft Excel add-in and has additional features for fold-change thresholding and block permutations. Here, we explain how the SAM methodology works in the context of a general approach to detecting differential gene expression in DNA microarrays. Some recently developed methodology for estimating false discovery rates and q-values has been included in the SAM software, which we summarize here.},
isbn = {978-0-387-21679-9},
langid = {english}
}
@article{StrongExpressionFOXP12004,
title = {Strong Expression of {{FOXP1}} Identifies a Distinct Subset of Diffuse Large {{B-cell}} Lymphoma ({{DLBCL}}) Patients with Poor Outcome},
date = {2004-10},
pages = {1--4}
}
@article{stuartSinglecellChromatinState2021,
title = {Single-Cell Chromatin State Analysis with {{Signac}}},
author = {Stuart, Tim and Srivastava, Avi and Madad, Shaista and Lareau, Caleb A. and Satija, Rahul},
date = {2021-11},
journaltitle = {Nature Methods},
shortjournal = {Nat Methods},
volume = {18},
number = {11},
eprint = {34725479},
eprinttype = {pmid},
pages = {1333--1341},
issn = {1548-7105},
doi = {10.1038/s41592-021-01282-5},
abstract = {The recent development of experimental methods for measuring chromatin state at single-cell resolution has created a need for computational tools capable of analyzing these datasets. Here we developed Signac, a comprehensive toolkit for the analysis of single-cell chromatin data. Signac enables an end-to-end analysis of single-cell chromatin data, including peak calling, quantification, quality control, dimension reduction, clustering, integration with single-cell gene expression datasets, DNA motif analysis and interactive visualization. Through its seamless compatibility with the Seurat package, Signac facilitates the analysis of diverse multimodal single-cell chromatin data, including datasets that co-assay DNA accessibility with gene expression, protein abundance and mitochondrial genotype. We demonstrate scaling of the Signac framework to analyze datasets containing over 700,000 cells.},
langid = {english},
keywords = {Bone Marrow Cells,Chromatin,Computational Biology,Gene Expression Profiling,Humans,Leukocytes Mononuclear,Mitochondria,Sequence Analysis DNA,Single-Cell Analysis,Software}
}
@article{sukBortezomibInhibitsBurkitt2015,
title = {Bortezomib Inhibits {{Burkitt}}'s Lymphoma Cell Proliferation by Downregulating Sumoylated {{hnRNP K}} and c-{{Myc}} Expression},
author = {Suk, Fat-Moon and Lin, Shyr-Yi and Lin, Ren-Jye and Hsine, Yung-Hsin and Liao, Yen-Ju and Fang, Sheng-Uei and Liang, Yu-Chih},
date = {2015-09-22},
journaltitle = {Oncotarget},
shortjournal = {Oncotarget},
volume = {6},
number = {28},
eprint = {26317903},
eprinttype = {pmid},
pages = {25988--26001},
issn = {1949-2553},
doi = {10.18632/oncotarget.4620},
abstract = {Bortezomib (Velcal) was the first proteasome inhibitor to be approved by the US Food and Drug Administration to treat patients with relapsed/refractory multiple myelomas. Previous studies have demonstrated that bortezomib inhibits tumor cell proliferation and induces apoptosis by blocking the nuclear factor (NF)-κB pathway. However, the exact mechanism by which bortezomib induces cancer cell apoptosis is still not well understood. In this study, we found that bortezomib significantly inhibited cell proliferation in both human Burkitt's lymphoma CA46 and Daudi cells. Through proteomic analysis, we found that bortezomib treatment changed the expression of various proteins in distinct functional categories including unfolding protein response (UPS), RNA processing, protein targeting and biosynthesis, apoptosis, and signal transduction. Among the proteins with altered expression, hnRNP K, hnRNP H, Hsp90α, Grp78, and Hsp7C were common to both Daudi and CA46 cells. Interestingly, bortezomib treatment downregulated the expression of high-molecular-weight (HMw) hnRNP K and c-Myc but upregulated the expression of low-molecular-weight (LMw) hnRNP K. Moreover, cell proliferation was significantly correlated with high expression of HMw hnRNP K and c-Myc. HMw and LMw hnRNP K were identified as sumoylated and desumoylated hnRNP K, respectively. Using transient transfection, we found that sumoylated hnRNP K increased c-Myc expression at the translational level and contributed to cell proliferation, and that Lys422 of hnRNP K is the candidate sumoylated residue. Our results suggest that besides inhibiting the ubiquitin-proteasome pathway, bortezomib may inhibit cell proliferation by downregulating sumoylated hnRNP K and c-Myc expression in Burkitt's lymphoma cells.},
langid = {english},
pmcid = {PMC4694880},
keywords = {Antineoplastic Agents,Bortezomib,Burkitt Lymphoma,Burkitt’s lymphoma,c-Myc,Cell Line Tumor,Cell Proliferation,Electrophoresis Gel Two-Dimensional,Endoplasmic Reticulum Chaperone BiP,Gene Expression Regulation Neoplastic,Heterogeneous-Nuclear Ribonucleoprotein K,hnRNP K,Humans,Immunoblotting,Lysine,Mutation,Proteomics,Proto-Oncogene Proteins c-myc,Spectrometry Mass Matrix-Assisted Laser Desorption-Ionization,sumoylation,Sumoylation}
}
@article{summersFrequencyBcl2IgH2001,
title = {Frequency of the {{Bcl-2}}/{{IgH}} Rearrangement in Normal Individuals: Implications for the Monitoring of Disease in Patients with Follicular Lymphoma},
shorttitle = {Frequency of the {{Bcl-2}}/{{IgH}} Rearrangement in Normal Individuals},
author = {Summers, K. E. and Goff, L. K. and Wilson, A. G. and Gupta, R. K. and Lister, T. A. and Fitzgibbon, J.},
date = {2001-01-15},
journaltitle = {Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology},
shortjournal = {J Clin Oncol},
volume = {19},
number = {2},
eprint = {11208834},
eprinttype = {pmid},
pages = {420--424},
issn = {0732-183X},
doi = {10.1200/JCO.2001.19.2.420},
abstract = {PURPOSE: To determine the incidence and frequency of the Bcl-2/IgH rearrangement in the peripheral blood of normal individuals to define the potential complication this may pose for the molecular monitoring of disease in patients with follicular lymphoma (FL). MATERIALS AND METHODS: The incidence and frequency of the major breakpoint cluster region rearrangement in DNA extracted from peripheral blood or lymphoblastoid cell lines from 481 normal individuals was determined using a TaqMan real-time polymerase chain reaction assay (PE Applied Biosystems, Foster City, CA). RESULTS: Twenty three percent of samples were positive for the Bcl-2/IgH rearrangement, with approximately 3\% of these at levels of more than 1 in 10(4) cells. CONCLUSION: The presence of circulating Bcl-2/IgH+ cells, other than those derived from the malignant clone, could confound the detection and quantitation of minimal residual disease in patients with FL, particularly at low levels of tumor burden.},
langid = {english},
keywords = {Adult,DNA,Gene Frequency,Gene Rearrangement,Genes bcl-2,Humans,Immunoglobulins,Lymphoma Follicular,Middle Aged,Neoplasm Residual,Oncogene Proteins Fusion,Polymerase Chain Reaction,Reference Values,Sequence Analysis DNA,Tumor Cells Cultured}
}
@article{sunCirculatingTumorCells2011,
title = {Circulating Tumor Cells: Advances in Detection Methods, Biological Issues, and Clinical Relevance.},
author = {Sun, Yun-Fan and Yang, Xin-Rong and Zhou, Jian and Qiu, Shuang-Jian and Fan, Jia and Xu, Yang},
date = {2011-08},
journaltitle = {Journal of cancer research and clinical oncology},
volume = {137},
number = {8},
pages = {1151--1173}
}
@article{sunProteinGeneExpression2016,
title = {Protein and Gene Expression Characteristics of Heterogeneous Nuclear Ribonucleoprotein {{H1}} in Esophageal Squamous Cell Carcinoma},
author = {Sun, Yu-Lin and Liu, Fei and Liu, Fang and Zhao, Xiao-Hang},
date = {2016-08-28},
journaltitle = {World Journal of Gastroenterology},
shortjournal = {World J Gastroenterol},
volume = {22},
number = {32},
eprint = {27621578},
eprinttype = {pmid},
pages = {7322--7331},
issn = {1007-9327},
doi = {10.3748/wjg.v22.i32.7322},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4997634/},
urldate = {2019-12-21},
abstract = {AIM To investigate the expression characteristics of heterogeneous nuclear ribonucleoprotein H1 (HNRNPH1) mRNA and protein in cell lines and tissues of esophageal squamous cell carcinoma (ESCC). METHODS Western blotting was used to assess the expression of HNRNPH1 protein in seven ESCC cell lines and 30 paired fresh tissue specimens. The subcellular localization of HNRNPH1 was determined by immunofluorescence in ESCC cells. The RNA sequencing data from 87 patients with ESCC were obtained from the cancer genome atlas (TCGA), and the expression and clinical characteristics analysis of different transcript variants of HNRNPH1 were evaluated in this dataset. In addition, immunohistochemistry was carried out to detect the expression of HNRNPH1 protein in 125 patients. RESULTS The expression of HNRNPH1 protein varied across different ESCC cell lines. It was exclusively restricted to the nucleus of the ESCC cells. There are two transcript variants of the HNRNPH1 gene. Variant 1 was constitutively expressed, and its expression did not change during tumorigenesis. In contrast, levels of variant 2 were low in non-tumorous tissues and were dramatically increased in ESCC (P = 0.0026). The high levels of variant 2 were associated with poorer differentiated tumors (P = 0.0287). Furthermore, in paired fresh tissue specimens, HNRNPH1 protein was overexpressed in 73.3\% (22/30) of neoplastic tissues. HNRNPH1 was significantly upregulated in ESCC, with strong staining in 43.2\% (54/125) of tumor tissues and 22.4\% (28/125) of matched non-cancerous tissues (P = 0.0005). Positive HNRNPH1 expression was significantly associated with poor tumor differentiation degree (P = 0.0337). CONCLUSION The different alternative transcript variants of HNRNPH1 exhibited different expression changes during tumorigenesis. Its mRNA and protein were overexpressed in ESCC and associated with poorer differentiation of tumor cells. These findings highlight the potential of HNRNPH1 in the therapy and diagnosis of ESCC.},
pmcid = {PMC4997634}
}
@article{svitkinControlTranslationMiRNADependent2013,
title = {Control of {{Translation}} and {{miRNA-Dependent Repression}} by a {{Novel Poly}}({{A}}) {{Binding Protein}}, {{hnRNP-Q}}},
author = {Svitkin, Yuri V. and Yanagiya, Akiko and Karetnikov, Alexey E. and Alain, Tommy and Fabian, Marc R. and Khoutorsky, Arkady and Perreault, Sandra and Topisirovic, Ivan and Sonenberg, Nahum},
date = {2013-05-21},
journaltitle = {PLOS Biology},
shortjournal = {PLOS Biology},
volume = {11},
number = {5},
pages = {e1001564},
publisher = {Public Library of Science},
issn = {1545-7885},
doi = {10.1371/journal.pbio.1001564},
url = {https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001564},
urldate = {2022-09-27},
abstract = {The heterogeneous nuclear ribonucleoprotein Q2 competitively binds mRNA poly(A) tails to regulate translational and miRNA-related functions of PABP.},
langid = {english},
keywords = {Cross-linking,Immunoprecipitation,Messenger RNA,Protein synthesis,Protein translation,Ribosomes,RNA extraction,Translation initiation}
}
@article{svitkinGeneralRNABinding1996,
title = {General {{RNA}} Binding Proteins Render Translation Cap Dependent},
author = {Svitkin, Y. V. and Ovchinnikov, L. P. and Dreyfuss, G. and Sonenberg, N.},
date = {1996-12-16},
journaltitle = {The EMBO journal},
shortjournal = {EMBO J},
volume = {15},
number = {24},
eprint = {9003790},
eprinttype = {pmid},
pages = {7147--7155},
issn = {0261-4189},
abstract = {Translation in rabbit reticulocyte lysate is relatively independent of the presence of the mRNA m7G cap structure and the cap binding protein, eIF-4E. In addition, initiation occurs frequently at spurious internal sites. Here we show that a critical parameter which contributes to cap-dependent translation is the amount of general RNA binding proteins in the extract. Addition of several general RNA binding proteins, such as hnRNP A1, La autoantigen, pyrimidine tract binding protein (hnRNP I/PTB) and the major core protein of cytoplasmic mRNP (p50), rendered translation in a rabbit reticulocyte lysate cap dependent. These proteins drastically inhibited the translation of an uncapped mRNA, but had no effect on translation of a capped mRNA. Based on these and other results, we suggest that one function of general mRNA binding proteins in the cytoplasm is to promote ribosome binding by a 5' end, cap-mediated mechanism, and prevent spurious initiations at aberrant translation start sites.},
langid = {english},
pmcid = {PMC452541},
keywords = {Animals,Eukaryotic Initiation Factor-4E,Peptide Initiation Factors,Protein Biosynthesis,Rabbits,Repressor Proteins,RNA Messenger,RNA-Binding Proteins}
}
@article{swerdlowWorldTurnsEvolving2020,
title = {As the World Turns, Evolving Lymphoma Classifications-Past, Present and Future},
author = {Swerdlow, Steven H. and Cook, James R.},
date = {2020-01},
journaltitle = {Human Pathology},
shortjournal = {Hum Pathol},
volume = {95},
eprint = {31493426},
eprinttype = {pmid},
pages = {55--77},
issn = {1532-8392},
doi = {10.1016/j.humpath.2019.08.019},
abstract = {The last century and a half has seen first the recognition of lymphomas, and then the publication of one lymphoma classification after another often together with highly critical comments about preceding classifications or a welcome that was less than warm. The introduction of HUMAN PATHOLOGY in 1970 came just before one of the very acrimonious periods in lymphoma classification, as we were learning more about the normal immune system and with the proposed functional lymphoma classifications of Lukes/Collins and Kiel in 1974 relating the lymphomas to their normal B-cell or T-cell 'counterparts'. Those difficult times were followed by the regressive strictly morphologic NCI Working Formulation in 1982, with the REAL classification in 1994 putting us back on a rational path, once again grouping the lymphoid neoplasms first into those of B-cell and T- and putative NK-cell origin, and then using multiple parameters to define specific entities. Planning for the first modern WHO lymphoma classification began soon afterward, with concordance and collegiality leading to the 2001 WHO classification, which then evolved with publication of the 2008 and 2016 WHO classifications. While this review looks at these important past developments which have gotten us to where we are today, it also concentrates on where we are now, what has been learned since the most recent WHO classification and 'Blue Book' were published and on some of the unanswered questions that remain as we look to the future.},
langid = {english},
keywords = {Biomarkers Tumor,Classification,Diffusion of Innovation,History 20th Century,History 21st Century,Humans,Kiel,Lukes/Collins,Lymphoma,Pathology,Rappaport,REAL,Terminology as Topic,WHO}
}
@article{takimotoSpecificBindingHeterogeneous1993,
title = {Specific Binding of Heterogeneous Ribonucleoprotein Particle Protein {{K}} to the Human C-Myc Promoter, in Vitro},
author = {Takimoto, M. and Tomonaga, T. and Matunis, M. and Avigan, M. and Krutzsch, H. and Dreyfuss, G. and Levens, D.},
date = {1993-08-25},
journaltitle = {The Journal of Biological Chemistry},
shortjournal = {J Biol Chem},
volume = {268},
number = {24},
eprint = {8349701},
eprinttype = {pmid},
pages = {18249--18258},
issn = {0021-9258},
abstract = {A homopurine/homopyrimidine-like sequence is found 100-150 base pairs upstream of the human c-myc promoter P1. This element, termed the CT-element, has been shown to augment expression from P1, and it serves as a positive transcriptional element when coupled to a heterologous promoter in vivo and in vitro. Synthetic oligonucleotides comprising this element were used to form DNA-protein complexes in electrophoretic mobility shift assays. By using conventional and affinity methods, 61- and 34-kDa proteins were shown to be associated with these complexes. Amino acid sequence analysis and immunological methods have identified these proteins as heterogeneous ribonucleoprotein particle (hnRNP) proteins K and A1. Surprisingly, hnRNP protein K binds to the pyrimidine-rich strand of the CT-element in a sequence-specific manner as well as to the double-stranded molecule. Cotransfection of vectors encoding hnRNP protein K in the sense or anti-sense orientations with reporter plasmids driven by wild-type or mutant CT-elements demonstrates that hnRNP protein K augments gene expression in a cis-element-dependent manner. Taken together, these results suggest that hnRNP protein K may play a role in the transcriptional regulation of the human c-myc gene.},
langid = {english},
keywords = {Amino Acid Sequence,Base Sequence,Cell Nucleus,Electrophoresis Polyacrylamide Gel,Genes myc,Genetic Vectors,HeLa Cells,Heterogeneous Nuclear Ribonucleoprotein A1,Heterogeneous-Nuclear Ribonucleoprotein Group A-B,Heterogeneous-Nuclear Ribonucleoproteins,Humans,Immunoblotting,Molecular Sequence Data,Molecular Weight,Oligodeoxyribonucleotides,Oligonucleotides Antisense,Peptide Fragments,Promoter Regions Genetic,Protein Binding,Ribonucleoproteins,RNA-Binding Proteins,Transfection}
}
@article{tamboreroOncodriveCISMethodReveal2013,
title = {Oncodrive-{{CIS}}: {{A Method}} to {{Reveal Likely Driver Genes Based}} on the {{Impact}} of {{Their Copy Number Changes}} on {{Expression}}},
author = {Tamborero, David and López-Bigas, Nuria and Gonzalez-Perez, Abel},
date = {2013-02},
journaltitle = {PloS one},
volume = {8},
number = {2},
pages = {e55489}
}
@article{tamboreroOncodriveCLUSTExploitingPositional2013,
title = {{{OncodriveCLUST}}: Exploiting the Positional Clustering of Somatic Mutations to Identify Cancer Genes},
shorttitle = {{{OncodriveCLUST}}},
author = {Tamborero, David and Gonzalez-Perez, Abel and Lopez-Bigas, Nuria},
date = {2013-09-15},
journaltitle = {Bioinformatics (Oxford, England)},
shortjournal = {Bioinformatics},
volume = {29},
number = {18},
eprint = {23884480},
eprinttype = {pmid},
pages = {2238--2244},
issn = {1367-4811},
doi = {10.1093/bioinformatics/btt395},
abstract = {MOTIVATION: Gain-of-function mutations often cluster in specific protein regions, a signal that those mutations provide an adaptive advantage to cancer cells and consequently are positively selected during clonal evolution of tumours. We sought to determine the overall extent of this feature in cancer and the possibility to use this feature to identify drivers. RESULTS: We have developed OncodriveCLUST, a method to identify genes with a significant bias towards mutation clustering within the protein sequence. This method constructs the background model by assessing coding-silent mutations, which are assumed not to be under positive selection and thus may reflect the baseline tendency of somatic mutations to be clustered. OncodriveCLUST analysis of the Catalogue of Somatic Mutations in Cancer retrieved a list of genes enriched by the Cancer Gene Census, prioritizing those with dominant phenotypes but also highlighting some recessive cancer genes, which showed wider but still delimited mutation clusters. Assessment of datasets from The Cancer Genome Atlas demonstrated that OncodriveCLUST selected cancer genes that were nevertheless missed by methods based on frequency and functional impact criteria. This stressed the benefit of combining approaches based on complementary principles to identify driver mutations. We propose OncodriveCLUST as an effective tool for that purpose. AVAILABILITY: OncodriveCLUST has been implemented as a Python script and is freely available from http://bg.upf.edu/oncodriveclust CONTACT: nuria.lopez@upf.edu or abel.gonzalez@upf.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.},
langid = {english},
keywords = {Cluster Analysis,Genes Neoplasm,Genomics,Humans,Mutation,Neoplasm Proteins,Sequence Analysis Protein,Software}
}
@article{tamIbrutinibVenetoclaxTreatment2018,
title = {Ibrutinib plus {{Venetoclax}} for the {{Treatment}} of {{Mantle-Cell Lymphoma}}},
author = {Tam, Constantine S. and Anderson, Mary Ann and Pott, Christiane and Agarwal, Rishu and Handunnetti, Sasanka and Hicks, Rodney J. and Burbury, Kate and Turner, Gillian and Di Iulio, Juliana and Bressel, Mathias and Westerman, David and Lade, Stephen and Dreyling, Martin and Dawson, Sarah-Jane and Dawson, Mark A. and Seymour, John F. and Roberts, Andrew W.},
date = {2018-03-29},
journaltitle = {The New England Journal of Medicine},
shortjournal = {N. Engl. J. Med.},
volume = {378},
number = {13},
eprint = {29590547},
eprinttype = {pmid},
pages = {1211--1223},
issn = {1533-4406},
doi = {10.1056/NEJMoa1715519},
abstract = {BACKGROUND: Both the BTK inhibitor ibrutinib and the BCL2 inhibitor venetoclax are active as monotherapy in the treatment of mantle-cell lymphoma. Complete response rates of 21\% have been observed for each agent when administered as long-term continuous therapy. Preclinical models predict synergy in combination. METHODS: We conducted a single-group, phase 2 study of daily oral ibrutinib and venetoclax in patients, as compared with historical controls. Patients commenced ibrutinib monotherapy at a dose of 560 mg per day. After 4 weeks, venetoclax was added in stepwise, weekly increasing doses to 400 mg per day. Both drugs were continued until progression or an unacceptable level of adverse events. The primary end point was the rate of complete response at week 16. Minimal residual disease (MRD) was assessed by flow cytometry in bone marrow and by allele-specific oligonucleotide-polymerase chain reaction (ASO-PCR) in blood. RESULTS: The study included 24 patients with relapsed or refractory mantle-cell lymphoma (23 patients) or previously untreated mantle-cell lymphoma (1 patient). Patients were 47 to 81 years of age, and the number of previous treatments ranged from none to six. Half the patients had aberrations of TP53, and 75\% had a high-risk prognostic score. The complete response rate according to computed tomography at week 16 was 42\%, which was higher than the historical result of 9\% at this time point with ibrutinib monotherapy (P{$<$}0.001). The rate of complete response as assessed by positron-emission tomography was 62\% at week 16 and 71\% overall. MRD clearance was confirmed by flow cytometry in 67\% of the patients and by ASO-PCR in 38\%. In a time-to-event analysis, 78\% of the patients with a response were estimated to have an ongoing response at 15 months. The tumor lysis syndrome occurred in 2 patients. Common side effects were generally low grade and included diarrhea (in 83\% of the patients), fatigue (in 75\%), and nausea or vomiting (in 71\%). CONCLUSIONS: In this study involving historical controls, dual targeting of BTK and BCL2 with ibrutinib and venetoclax was consistent with improved outcomes in patients with mantle-cell lymphoma who had been predicted to have poor outcomes with current therapy. (Funded by Janssen and others; AIM ClinicalTrials.gov number, NCT02471391 .).},
langid = {english},
keywords = {Administration Oral,Agammaglobulinaemia Tyrosine Kinase,Aged,Aged 80 and over,Antineoplastic Combined Chemotherapy Protocols,Bone Marrow Examination,Bridged Bicyclo Compounds Heterocyclic,Disease-Free Survival,Female,Historically Controlled Study,Humans,Intention to Treat Analysis,Lymph Nodes,Lymphoma Mantle-Cell,Male,Middle Aged,Mutation,Neoplasm Residual,Prognosis,Protein Kinase Inhibitors,Protein-Tyrosine Kinases,Proto-Oncogene Proteins c-bcl-2,Pyrazoles,Pyrimidines,Sulfonamides,Survival Rate}
}
@article{tamMutationalAnalysisPRDM12006,
title = {Mutational Analysis of {{PRDM1}} Indicates a Tumor-Suppressor Role in Diffuse Large {{B-cell}} Lymphomas},
author = {Tam, W},
date = {2006-05},
journaltitle = {Blood},
volume = {107},
number = {10},
pages = {4090--4100}
}
@article{tanakaFrequentIncidenceSomatic1992,
title = {Frequent Incidence of Somatic Mutations in Translocated {{BCL2}} Oncogenes of Non-{{Hodgkin}}'s Lymphomas},
author = {Tanaka, S. and Louie, D. C. and Kant, J. A. and Reed, J. C.},
date = {1992-01-01},
journaltitle = {Blood},
shortjournal = {Blood},
volume = {79},
number = {1},
eprint = {1339299},
eprinttype = {pmid},
pages = {229--237},
issn = {0006-4971},
doi = {10.1182/blood.V79.1.229.229},
abstract = {The majority of non-Hodgkin's B-cell lymphomas contain a t(14;18) translocation that places the bc12 gene into juxtaposition with the transcriptically active Ig heavy-chain locus, thus deregulating the expression of this proto-oncogene. The bc12 gene product is a membrane-associated mitochondrial protein that regulates cell survival through unknown mechanisms. Although overproduction of the normal protein appears sufficient for conferring a selective growth or survival advantage to B cells, point mutations that alter the coding region of translocated bc12 genes have been described previously by others in a lymphoma cell line. However, it is not known whether somatic mutations that alter BCL2 proteins occur in vivo or whether they result from chemotherapy or arise through other mechanisms. For these reasons, we obtained DNA from the t(14;18)-containing tumors of five patients who had not undergone treatment for their disease, and used a polymerase chain reaction (PCR)-mismatch technique for rapid identification of point mutations in a portion of the bc12 open reading frame (ORF) corresponding to the first 131 aminoacids (aa) of the 239 aa p26 BCL2 protein. DNAs from two t(14;18)-containing cell lines were also analyzed. Point mutations in this region of the bc12 gene ORF were detected in three of five patients' tumors and in both cell lines. PCR-mismatch analysis of bc12 in cell lines and non-Hodgkin's lymphoma cases that lacked the t(14;18) translocation was negative, thus establishing the specificity of these results. DNA sequencing determined that these mutations are predicted to produce aa substitutions in the BCL2 proteins of two of the primary tumors and one of the cell lines. Interestingly, two of the patients contained an identical C----T transition that resulted in a nonconservative aa substitution (proline----serine) at position 59 of the BCL2 protein. Further analysis excluded the possibility that these mutations represented hereditary polymorphisms or PCR artifacts. A cluster of four point mutations within the translocation + bc12 allele of one patient had hallmarks of the somatic hypermutation mechanism that is associated with Ig genes and that contributes to antibody diversity. Because of the region of the bcl2 gene analyzed in these t(14;18) translocations is located nearly 300 kbp from the Ig heavy-chain locus, our data suggest that the Ig gene somatic hypermutation mechanism can act over extreme distances of DNA. It remains to be established whether these somatic mutations that alter BCL2 proteins influence the pathobiology of nonHodgkin's lymphomas.},
langid = {english},
keywords = {Base Sequence,Chromosomes Human Pair 14,Chromosomes Human Pair 18,DNA Neoplasm,Humans,Lymphoma Non-Hodgkin,Molecular Sequence Data,Mutation,Polymerase Chain Reaction,Proto-Oncogene Mas,Proto-Oncogene Proteins,Proto-Oncogene Proteins c-bcl-2,Translocation Genetic,Tumor Cells Cultured}
}
@article{tangHnRNPA2B1PromotesColon2021,
title = {{{hnRNPA2B1 Promotes Colon Cancer Progression}} via the {{MAPK Pathway}}},
author = {Tang, Jingzhi and Chen, Zhimin and Wang, Qi and Hao, Weijie and Gao, Wei-Qiang and Xu, Huiming},
date = {2021},
journaltitle = {Frontiers in Genetics},
volume = {12},
issn = {1664-8021},
url = {https://www.frontiersin.org/articles/10.3389/fgene.2021.666451},
urldate = {2022-10-04},
abstract = {HNRNPA2B1, an RNA-binding protein, plays a key role in primary microRNA processing, alternative splicing, mRNA metabolism and transport. Interestingly, hnRNPA2B1 also works as an N6-methyladenosine (m6A) reader and is critical during tumorigenesis of various tissue types. However, its role in colon cancer is still unclear. In this study, we aimed to elucidate the biological functions of hnRNPA2B1 and to explore its underlying mechanisms in colon cancer. We examined the expression of hnRNPA2B1 in Oncomine and TCGA databases. Then verified the findings in colon cancer cells and clinical samples with western blotting and immunohistochemistry (IHC). We used CRISPR/Cas9 directed gene editing to knockout hnRNPA2B1 expression in human colon cancer cell line SW480 and HCT-116 and carried out both in vivo and in vitro experiments. The results were further confirmed by RNA-seq analyses. We found that hnRNPA2B1 significantly promoted colon cancer cell proliferation both in vitro and in vivo, while knockout of hnRNPA2B1 induced apoptosis and cell cycle arrest in SW480. RNA-seq analyses revealed that the ERK/MAPK pathway was activated by hnRNPA2B1 upregulation. In addition, both hnRNPA2B1 and MAPK pathway were activated in clinical colon cancer specimens and positively correlated. Mechanistically, hnRNPA2B1 appeared to be an upstream regulator of the ERK/MAPK pathway and inhibition of MAPK signaling blocked the effects of hnRNPA2B1. Taken together, our data demonstrated that the RNA-binding protein hnRNPA2B1 promotes cell proliferation and regulates cell cycle and apoptosis of human colon cancer by activating the ERK/MAPK signaling, which may provide a new insight into the development of hnRNPA2B1 as a potential therapeutic target for treatment of colon cancer.}
}
@article{tangIDogIntegratedResource2019,
title = {{{iDog}}: An Integrated Resource for Domestic Dogs and Wild Canids},
shorttitle = {{{iDog}}},
author = {Tang, Bixia and Zhou, Qing and Dong, Lili and Li, Wulue and Zhang, Xiangquan and Lan, Li and Zhai, Shuang and Xiao, Jingfa and Zhang, Zhang and Bao, Yiming and Zhang, Ya-Ping and Wang, Guo-Dong and Zhao, Wenming},
date = {2019-01-08},
journaltitle = {Nucleic Acids Research},
shortjournal = {Nucleic Acids Research},
volume = {47},
number = {D1},
pages = {D793-D800},
issn = {0305-1048},
doi = {10.1093/nar/gky1041},
url = {https://doi.org/10.1093/nar/gky1041},
urldate = {2021-05-13},
abstract = {The domestic dog (Canis lupus familiaris) is indisputably one of man's best friends. It is also a fundamental model for many heritable human diseases. Here, we present iDog (http://bigd.big.ac.cn/idog), the first integrated resource dedicated to domestic dogs and wild canids. It incorporates a variety of omics data, including genome sequences assemblies for dhole and wolf, genomic variations extracted from hundreds of dog/wolf whole genomes, phenotype/disease traits curated from dog research communities and public resources, gene expression profiles derived from published RNA-Seq data, gene ontology for functional annotation, homolog gene information for multiple organisms and disease-related literature. Additionally, iDog integrates sequence alignment tools for data analyses and a genome browser for data visualization. iDog will not only benefit the global dog research community, but also provide access to a user-friendly consolidation of dog information to a large number of dog enthusiasts.}
}
@article{taniOverexpressionHeterogeneousNuclear2002,
title = {Overexpression of Heterogeneous Nuclear Ribonucleoprotein {{B1}} in Lymphoproliferative Disorders: {{High}} Expression in Cells of Follicular Center Origin},
shorttitle = {Overexpression of Heterogeneous Nuclear Ribonucleoprotein {{B1}} in Lymphoproliferative Disorders},
author = {Tani, Hiroki and Ohshima, Koichi and Haraoka, Seiji and Hamasaki, Makoto and Kamma, Hiroshi and Ikeda, Seiyo and Kikuchi, Masahiro},
date = {2002-11-01},
journaltitle = {International Journal of Oncology},
volume = {21},
number = {5},
pages = {957--963},
publisher = {Spandidos Publications},
issn = {1019-6439},
doi = {10.3892/ijo.21.5.957},
url = {https://www.spandidos-publications.com/10.3892/ijo.21.5.957},
urldate = {2022-10-04},
abstract = {It is reported that overexpression of hnRNP A2 and B1 proteins is useful for detecting early cancers, and that B1, a splicing minor isoform of A2, is more specific than A2. The B1 expression is still undetermined in human lymphoid tissues. We quantitatively studied the B1 expression in 85 lymph node specimens, comprising reactive lymphoid hyperplasia (RLH; n=8), B-cell lymphoma (n=23), T-cell lymphoma (n=22), and metastatic carcinoma (n=32). Immunostaining and immunoblotting analyses with an anti-B1 monoclonal antibody, 2B2 were performed, and the two sets of results correlated with each other (p{$<$}0.05). In RLH specimens, B1 expression rate was significantly higher in follicular centers (FC; 44\%) than in mantle zone (MZ; 15\%) and paracortex (16\%) (p{$<$}0.01). B1 expression was statistically higher in B-cell lymphoma than in T-cell lymphoma (p{$<$}0.01). In B-cell lymphomas, B1 expression rates were 51\% in diffuse large B-cell lymphoma (DLBL; n=5) and 45\% in follicular lymphoma (FL; n=16), and they were almost the same as that of the FC. Especially in DLBLs, CD10+ FC-origin lymphomas expressed greater amount of B1 than CD10- non-FC-origin lymphomas. B1 expression rate was low in mantle cell lymphoma (MCL; n=2) and similar to that of MZ in RLH. These results suggest that B1 expression is associated with differentiation in lymphoid tissue rather than transformation. B1 expression increases during the process of B-cell differentiation in the FC, and that high B1 expression is maintained in B-cell lymphomagenesis, especially in cells of FC-origin DLBL.}
}
@article{taniReducedExpressionHeterogeneous2003,
title = {Reduced Expression of Heterogeneous Nuclear Ribonucleoprotein {{B1}} in Adult {{T-cell}} Lymphoma/Leukemia},
author = {Tani, Hiroki and Ohshima, Koichi and Haraoka, Seiji and Hamasaki, Makoto and Kamma, Hiroshi and Ikeda, Seiyo and Kikuchi, Masahiro},
date = {2003-03-01},
journaltitle = {International Journal of Oncology},
volume = {22},
number = {3},
pages = {529--534},
publisher = {Spandidos Publications},
issn = {1019-6439},
doi = {10.3892/ijo.22.3.529},
url = {https://www.spandidos-publications.com/10.3892/ijo.22.3.529},
urldate = {2022-10-04},
abstract = {It is considered that hnRNP B1 expresses similarly in the various types of tumor cells. Recently, we demonstrated high B1 expression in B-cell lymphoma and carcinoma. To evaluate the difference of B1 expression between B and T-cell lymphoma, we immunologically studied the B1 expression in 22 cases with nodal T-cell lymphoma, comprising adult T-cell leukemia/lymphoma (ATLL; n=15) and angioimmunoblastic T-cell lymphoma (AILD; n=7), using an anti-hnRNP B1 monoclonal antibody, 2B2. In ATLL cases, scattered large transformed lymphoma cells demonstrated strong B1 expression, while the medium-sized lymphoma cells were negative. On the one hand, lymphoma cells in AILD diffusely expressed B1. The mean B1 expression rate in ATLL was 22\%, which was significantly lower than that in AILDs (45\%), B-cell lymphomas (44\%), and metastatic carcinomas (53\%) (p{$<$}0.01). Our result might suggest that process of hnRNP B1 expression in ATLL differs from those in other lymphoid neoplasms and carcinoma.}
}
@article{tarabichiPracticalGuideCancer2021,
title = {A Practical Guide to Cancer Subclonal Reconstruction from {{DNA}} Sequencing},
author = {Tarabichi, Maxime and Salcedo, Adriana and Deshwar, Amit G. and Ni Leathlobhair, Máire and Wintersinger, Jeff and Wedge, David C. and Van Loo, Peter and Morris, Quaid D. and Boutros, Paul C.},
date = {2021-02},
journaltitle = {Nature Methods},
shortjournal = {Nat Methods},
volume = {18},
number = {2},
eprint = {33398189},
eprinttype = {pmid},
pages = {144--155},
issn = {1548-7105},
doi = {10.1038/s41592-020-01013-2},
abstract = {Subclonal reconstruction from bulk tumor DNA sequencing has become a pillar of cancer evolution studies, providing insight into the clonality and relative ordering of mutations and mutational processes. We provide an outline of the complex computational approaches used for subclonal reconstruction from single and multiple tumor samples. We identify the underlying assumptions and uncertainties in each step and suggest best practices for analysis and quality assessment. This guide provides a pragmatic resource for the growing user community of subclonal reconstruction methods.},
langid = {english},
pmcid = {PMC7867630},
keywords = {Algorithms,DNA Neoplasm,Humans,Neoplasms,Polymorphism Single Nucleotide,Sequence Analysis DNA}
}
@article{tarellaProlongedSurvivalPoorrisk2007,
title = {Prolonged Survival in Poor-Risk Diffuse Large {{B-cell}} Lymphoma Following Front-Line Treatment with Rituximab-Supplemented, Early-Intensified Chemotherapy with Multiple Autologous Hematopoietic Stem Cell Support: A Multicenter Study by {{GITIL}} ({{Gruppo Italiano Terapie Innovative}} Nei {{Linfomi}})},
author = {Tarella, C and Zanni, M and Di Nicola, M and Patti, C and Calvi, R and Pescarollo, A and Zoli, V and Fornari, A and Novero, D and Cabras, A and Stella, M and Comino, A and Remotti, D and Ponzoni, M and Caracciolo, D and Ladetto, M and Magni, M and Devizzi, L and Rosato, R and Boccadoro, M and Bregni, M and Corradini, P and Gallamini, A and Majolino, I and Mirto, S and Gianni, A M and family=Linfomi, given=Gruppo Italiano Terapie Innovative, prefix=nei, useprefix=false},
date = {2007-08},
journaltitle = {Leukemia},
volume = {21},
number = {8},
pages = {1802--1811}
}
@article{taylorGenomeNorthAmerican2018,
title = {The {{Genome}} of the {{North American Brown Bear}} or {{Grizzly}}: {{Ursus}} Arctos Ssp. Horribilis},
shorttitle = {The {{Genome}} of the {{North American Brown Bear}} or {{Grizzly}}},
author = {Taylor, Gregory A. and Kirk, Heather and Coombe, Lauren and Jackman, Shaun D. and Chu, Justin and Tse, Kane and Cheng, Dean and Chuah, Eric and Pandoh, Pawan and Carlsen, Rebecca and Zhao, Yongjun and Mungall, Andrew J. and Moore, Richard and Birol, Inanc and Franke, Maria and Marra, Marco A. and Dutton, Christopher and Jones, Steven J. M.},
date = {2018-11-30},
journaltitle = {Genes},
shortjournal = {Genes (Basel)},
volume = {9},
number = {12},
eprint = {30513700},
eprinttype = {pmid},
pages = {E598},
issn = {2073-4425},
doi = {10.3390/genes9120598},
abstract = {The grizzly bear (Ursus arctos ssp. horribilis) represents the largest population of brown bears in North America. Its genome was sequenced using a microfluidic partitioning library construction technique, and these data were supplemented with sequencing from a nanopore-based long read platform. The final assembly was 2.33 Gb with a scaffold N50 of 36.7 Mb, and the genome is of comparable size to that of its close relative the polar bear (2.30 Gb). An analysis using 4104 highly conserved mammalian genes indicated that 96.1\% were found to be complete within the assembly. An automated annotation of the genome identified 19,848 protein coding genes. Our study shows that the combination of the two sequencing modalities that we used is sufficient for the construction of highly contiguous reference quality mammalian genomes. The assembled genome sequence and the supporting raw sequence reads are available from the NCBI (National Center for Biotechnology Information) under the bioproject identifier PRJNA493656, and the assembly described in this paper is version QXTK01000000.},
langid = {english},
pmcid = {PMC6315469},
keywords = {genome,grizzly bear,microfluidic partitioning,nanopore,Ursus arctos ssp. Horribilis}
}
@article{taylorPromotingCoherentMinimum2008,
title = {Promoting Coherent Minimum Reporting Guidelines for Biological and Biomedical Investigations: The {{MIBBI}} Project},
shorttitle = {Promoting Coherent Minimum Reporting Guidelines for Biological and Biomedical Investigations},
author = {Taylor, Chris F. and Field, Dawn and Sansone, Susanna-Assunta and Aerts, Jan and Apweiler, Rolf and Ashburner, Michael and Ball, Catherine A. and Binz, Pierre-Alain and Bogue, Molly and Booth, Tim and Brazma, Alvis and Brinkman, Ryan R. and Michael Clark, Adam and Deutsch, Eric W. and Fiehn, Oliver and Fostel, Jennifer and Ghazal, Peter and Gibson, Frank and Gray, Tanya and Grimes, Graeme and Hancock, John M. and Hardy, Nigel W. and Hermjakob, Henning and Julian, Randall K. and Kane, Matthew and Kettner, Carsten and Kinsinger, Christopher and Kolker, Eugene and Kuiper, Martin and Novère, Nicolas Le and Leebens-Mack, Jim and Lewis, Suzanna E. and Lord, Phillip and Mallon, Ann-Marie and Marthandan, Nishanth and Masuya, Hiroshi and McNally, Ruth and Mehrle, Alexander and Morrison, Norman and Orchard, Sandra and Quackenbush, John and Reecy, James M. and Robertson, Donald G. and Rocca-Serra, Philippe and Rodriguez, Henry and Rosenfelder, Heiko and Santoyo-Lopez, Javier and Scheuermann, Richard H. and Schober, Daniel and Smith, Barry and Snape, Jason and Stoeckert, Christian J. and Tipton, Keith and Sterk, Peter and Untergasser, Andreas and Vandesompele, Jo and Wiemann, Stefan},
date = {2008-08},
journaltitle = {Nature Biotechnology},
shortjournal = {Nat Biotechnol},
volume = {26},
number = {8},
pages = {889--896},
publisher = {Nature Publishing Group},
issn = {1546-1696},
doi = {10.1038/nbt.1411},
url = {https://www.nature.com/articles/nbt.1411},
urldate = {2022-05-19},
abstract = {The Minimum Information for Biological and Biomedical Investigations (MIBBI) project aims to foster the coordinated development of minimum-information checklists and provide a resource for those exploring the range of extant checklists.},
issue = {8},
langid = {english},
keywords = {Agriculture,Bioinformatics,Biomedical Engineering/Biotechnology,Biomedicine,Biotechnology,general,Life Sciences}
}
@article{teraaImpactSF3B1Mutations2015,
title = {The Impact of {{SF3B1}} Mutations in {{CLL}} on the {{DNA-damage}} Response},
author = {Te Raa, G. D. and Derks, I. a. M. and Navrkalova, V. and Skowronska, A. and Moerland, P. D. and family=Laar, given=J., prefix=van, useprefix=true and Oldreive, C. and Monsuur, H. and Trbusek, M. and Malcikova, J. and Lodén, M. and Geisler, C. H. and Hüllein, J. and Jethwa, A. and Zenz, T. and Pospisilova, S. and Stankovic, T. and family=Oers, given=M. H. J., prefix=van, useprefix=true and Kater, A. P. and Eldering, E.},
date = {2015-05},
journaltitle = {Leukemia},
shortjournal = {Leukemia},
volume = {29},
number = {5},
eprint = {25371178},
eprinttype = {pmid},
pages = {1133--1142},
issn = {1476-5551},
doi = {10.1038/leu.2014.318},
abstract = {Mutations or deletions in TP53 or ATM are well-known determinants of poor prognosis in chronic lymphocytic leukemia (CLL), but only account for approximately 40\% of chemo-resistant patients. Genome-wide sequencing has uncovered novel mutations in the splicing factor sf3b1, that were in part associated with ATM aberrations, suggesting functional synergy. We first performed detailed genetic analyses in a CLL cohort (n=110) containing ATM, SF3B1 and TP53 gene defects. Next, we applied a newly developed multiplex assay for p53/ATM target gene induction and measured apoptotic responses to DNA damage. Interestingly, SF3B1 mutated samples without concurrent ATM and TP53 aberrations (sole SF3B1) displayed partially defective ATM/p53 transcriptional and apoptotic responses to various DNA-damaging regimens. In contrast, NOTCH1 or K/N-RAS mutated CLL displayed normal responses in p53/ATM target gene induction and apoptosis. In sole SF3B1 mutated cases, ATM kinase function remained intact, and γH2AX formation, a marker for DNA damage, was increased at baseline and upon irradiation. Our data demonstrate that single mutations in sf3b1 are associated with increased DNA damage and/or an aberrant response to DNA damage. Together, our observations may offer an explanation for the poor prognosis associated with SF3B1 mutations.},
langid = {english},
keywords = {Apoptosis,Ataxia Telangiectasia Mutated Proteins,Cohort Studies,DNA Damage,DNA Mutational Analysis,Doxorubicin,Flow Cytometry,Gene Deletion,Gene Expression Regulation Leukemic,Genome Human,Histones,Humans,Imidazoles,Leukemia Lymphocytic Chronic B-Cell,Mutation,Phosphoproteins,Piperazines,Prognosis,Receptor Notch1,Ribonucleoprotein U2 Small Nuclear,RNA Splicing Factors,Tumor Suppressor Protein p53,Vidarabine}
}
@article{teschendorffConsensusPrognosticGene2006,
title = {A Consensus Prognostic Gene Expression Classifier for {{ER}} Positive Breast Cancer},
author = {Teschendorff, Andrew E. and Naderi, Ali and Barbosa-Morais, Nuno L. and Pinder, Sarah E. and Ellis, Ian O. and Aparicio, Sam and Brenton, James D. and Caldas, Carlos},
date = {2006},
journaltitle = {Genome Biology},
shortjournal = {Genome Biol.},
volume = {7},
number = {10},
eprint = {17076897},
eprinttype = {pmid},
pages = {R101},
issn = {1474-760X},
doi = {10.1186/gb-2006-7-10-r101},
abstract = {BACKGROUND: A consensus prognostic gene expression classifier is still elusive in heterogeneous diseases such as breast cancer. RESULTS: Here we perform a combined analysis of three major breast cancer microarray data sets to hone in on a universally valid prognostic molecular classifier in estrogen receptor (ER) positive tumors. Using a recently developed robust measure of prognostic separation, we further validate the prognostic classifier in three external independent cohorts, confirming the validity of our molecular classifier in a total of 877 ER positive samples. Furthermore, we find that molecular classifiers may not outperform classical prognostic indices but that they can be used in hybrid molecular-pathological classification schemes to improve prognostic separation. CONCLUSION: The prognostic molecular classifier presented here is the first to be valid in over 877 ER positive breast cancer samples and across three different microarray platforms. Larger multi-institutional studies will be needed to fully determine the added prognostic value of molecular classifiers when combined with standard prognostic factors.},
langid = {english},
pmcid = {PMC1794561},
keywords = {Breast Neoplasms,Cohort Studies,Female,Gene Expression Profiling,Genetic Markers,Humans,Oligonucleotide Array Sequence Analysis,Prognosis,Receptors Estrogen,Reproducibility of Results}
}
@article{testoniGainsMYCLocus,
title = {Gains of {{MYC}} Locus and Outcome in Patients with Diffuse Large {{B-cell}} Lymphoma Treated with {{R-CHOP}}.},
author = {Testoni, Monica and Kwee, Ivo and Greiner, Timothy C and Montes-Moreno, Santiago and Vose, Julie and Chan, Wing C and Chiappella, Annalisa and Baldini, Luca and Ferreri, Andrés J M and Gaidano, Gianluca and Mian, Michael and Zucca, Emanuele and Bertoni, Francesco},
journaltitle = {Br J Haematol},
volume = {155},
number = {2},
pages = {274--277}
}
@article{thierryClinicalValidationDetection,
title = {Clinical Validation of the Detection of {{KRAS}} and {{BRAF}} Mutations from Circulating Tumor {{DNA}}},
author = {Thierry, Alain R and Mouliere, Florent and El Messaoudi, Safia and Mollevi, Caroline and Lopez-Crapez, Evelyne and Rolet, Fanny and Gillet, Brigitte and Gongora, Celine and Dechelotte, Pierre and Robert, Bruno and Del Rio, Maguy and Lamy, Pierre-Jean and Bibeau, Frederic and Nouaille, Michelle and Loriot, Virginie and Jarrousse, Anne-Sophie and Molina, Franck and Mathonnet, Muriel and Pezet, Denis and Ychou, Marc},
journaltitle = {Nature Medicine},
pages = {1--7}
}
@article{thomasGeneticSubgroupsInform2023,
title = {Genetic Subgroups Inform on Pathobiology in Adult and Pediatric {{Burkitt}} Lymphoma},
author = {Thomas, Nicole and Dreval, Kostiantyn and Gerhard, Daniela S. and Hilton, Laura K. and Abramson, Jeremy S. and Ambinder, Richard F. and Barta, Stefan and Bartlett, Nancy L. and Bethony, Jeffrey and Bhatia, Kishor and Bowen, Jay and Bryan, Anthony C. and Cesarman, Ethel and Casper, Corey and Chadburn, Amy and Cruz, Manuela and Dittmer, Dirk P. and Dyer, Maureen A. and Farinha, Pedro and Gastier-Foster, Julie M. and Gerrie, Alina S. and Grande, Bruno M. and Greiner, Timothy and Griner, Nicholas B. and Gross, Thomas G. and Harris, Nancy L. and Irvin, John D. and Jaffe, Elaine S. and Henry, David and Huppi, Rebecca and Leal, Fabio E. and Lee, Michael S. and Martin, Jean Paul and Martin, Marie-Reine and Mbulaiteye, Sam M. and Mitsuyasu, Ronald and Morris, Vivian and Mullighan, Charles G. and Mungall, Andrew J. and Mungall, Karen and Mutyaba, Innocent and Nokta, Mostafa and Namirembe, Constance and Noy, Ariela and Ogwang, Martin D. and Omoding, Abraham and Orem, Jackson and Ott, German and Petrello, Hilary and Pittaluga, Stefania and Phelan, James D. and Ramos, Juan Carlos and Ratner, Lee and Reynolds, Steven J. and Rubinstein, Paul G. and Sissolak, Gerhard and Slack, Graham and Soudi, Shaghayegh and Swerdlow, Steven H. and Traverse-Glehen, Alexandra and Wilson, Wyndham H. and Wong, Jasper and Yarchoan, Robert and ZenKlusen, Jean C. and Marra, Marco A. and Staudt, Louis M. and Scott, David W. and Morin, Ryan D.},
date = {2023-02-23},
journaltitle = {Blood},
shortjournal = {Blood},
volume = {141},
number = {8},
pages = {904--916},
issn = {0006-4971},
doi = {10.1182/blood.2022016534},
pmcid = {PMC10023728},
abstract = {Burkitt lymphoma (BL) accounts for most pediatric non-Hodgkin lymphomas, being less common but significantly more lethal when diagnosed in adults. Much of the knowledge of the genetics of BL thus far has originated from the study of pediatric BL (pBL), leaving its relationship to adult BL (aBL) and other adult lymphomas not fully explored. We sought to more thoroughly identify the somatic changes that underlie lymphomagenesis in aBL and any molecular features that associate with clinical disparities within and between pBL and aBL. Through comprehensive whole-genome sequencing of 230 BL and 295 diffuse large B-cell lymphoma (DLBCL) tumors, we identified additional significantly mutated genes, including more genetic features that associate with tumor Epstein-Barr virus status, and unraveled new distinct subgroupings within BL and DLBCL with 3 predominantly comprising BLs: DGG-BL (DDX3X, GNA13, and GNAI2), IC-BL (ID3 and CCND3), and Q53-BL (quiet TP53). Each BL subgroup is characterized by combinations of common driver and noncoding mutations caused by aberrant somatic hypermutation. The largest subgroups of BL cases, IC-BL and DGG-BL, are further characterized by distinct biological and gene expression differences. IC-BL and DGG-BL and their prototypical genetic features (ID3 and TP53) had significant associations with patient outcomes that were different among aBL and pBL cohorts. These findings highlight shared pathogenesis between aBL and pBL, and establish genetic subtypes within BL that serve to delineate tumors with distinct molecular features, providing a new framework for epidemiologic, diagnostic, and therapeutic strategies.},
keywords = {Morinlab}
}
@article{tiacciAnalyzingPrimaryHodgkin2012,
title = {Analyzing Primary {{Hodgkin}} and {{Reed-Sternberg}} Cells to Capture the Molecular and Cellular Pathogenesis of Classical {{Hodgkin}} Lymphoma},
author = {Tiacci, Enrico and Döring, Claudia and Brune, Verena and family=Noesel, given=Carel J. M., prefix=van, useprefix=true and Klapper, Wolfram and Mechtersheimer, Gunhild and Falini, Brunangelo and Küppers, Ralf and Hansmann, Martin-Leo},
date = {2012-11-29},
journaltitle = {Blood},
shortjournal = {Blood},
volume = {120},
number = {23},
eprint = {22955914},
eprinttype = {pmid},
pages = {4609--4620},
issn = {1528-0020},
doi = {10.1182/blood-2012-05-428896},
abstract = {The pathogenesis of classical Hodgkin lymphoma (cHL), the most common lymphoma in the young, is still enigmatic, largely because its Hodgkin and Reed-Sternberg (HRS) tumor cells are rare in the involved lymph node and therefore difficult to analyze. Here, by overcoming this technical challenge and performing, for the first time, a genome-wide transcriptional analysis of microdissected HRS cells compared with other B-cell lymphomas, cHL lines, and normal B-cell subsets, we show that they differ extensively from the usually studied cHL cell lines, that the lost B-cell identity of cHLs is not linked to the acquisition of a plasma cell-like gene expression program, and that Epstein-Barr virus infection of HRS cells has a minor transcriptional influence on the established cHL clone. Moreover, although cHL appears a distinct lymphoma entity overall, HRS cells of its histologic subtypes diverged in their similarity to other related lymphomas. Unexpectedly, we identified 2 molecular subgroups of cHL associated with differential strengths of the transcription factor activity of the NOTCH1, MYC, and IRF4 proto-oncogenes. Finally, HRS cells display deregulated expression of several genes potentially highly relevant to lymphoma pathogenesis, including silencing of the apoptosis-inducer BIK and of INPP5D, an inhibitor of the PI3K-driven oncogenic pathway.},
langid = {english},
keywords = {Adult,Apoptosis Regulatory Proteins,B-Lymphocytes,Cell Line Tumor,Cells Cultured,Cluster Analysis,Gene Expression Profiling,Gene Expression Regulation Neoplastic,Hodgkin Disease,Humans,Immunohistochemistry,Inositol Polyphosphate 5-Phosphatases,Lymphoma B-Cell,Membrane Proteins,Mitochondrial Proteins,Oligonucleotide Array Sequence Analysis,Phosphatidylinositol-345-Trisphosphate 5-Phosphatases,Phosphoric Monoester Hydrolases,Reed-Sternberg Cells,Tumor Cells Cultured,Tumor Microenvironment}
}
@article{tiacciBRAFMutationsHairycell2011,
title = {{{BRAF}} Mutations in Hairy-Cell Leukemia},
author = {Tiacci, Enrico and Trifonov, Vladimir and Schiavoni, Gianluca and Holmes, Antony and Kern, Wolfgang and Martelli, Maria Paola and Pucciarini, Alessandra and Bigerna, Barbara and Pacini, Roberta and Wells, Victoria A. and Sportoletti, Paolo and Pettirossi, Valentina and Mannucci, Roberta and Elliott, Oliver and Liso, Arcangelo and Ambrosetti, Achille and Pulsoni, Alessandro and Forconi, Francesco and Trentin, Livio and Semenzato, Gianpietro and Inghirami, Giorgio and Capponi, Monia and Di Raimondo, Francesco and Patti, Caterina and Arcaini, Luca and Musto, Pellegrino and Pileri, Stefano and Haferlach, Claudia and Schnittger, Susanne and Pizzolo, Giovanni and Foà, Robin and Farinelli, Laurent and Haferlach, Torsten and Pasqualucci, Laura and Rabadan, Raul and Falini, Brunangelo},
date = {2011-06-16},
journaltitle = {The New England Journal of Medicine},
shortjournal = {N Engl J Med},
volume = {364},
number = {24},
eprint = {21663470},
eprinttype = {pmid},
pages = {2305--2315},
issn = {1533-4406},
doi = {10.1056/NEJMoa1014209},
abstract = {BACKGROUND: Hairy-cell leukemia (HCL) is a well-defined clinicopathological entity whose underlying genetic lesion is still obscure. METHODS: We searched for HCL-associated mutations by performing massively parallel sequencing of the whole exome of leukemic and matched normal cells purified from the peripheral blood of an index patient with HCL. Findings were validated by Sanger sequencing in 47 additional patients with HCL. RESULTS: Whole-exome sequencing identified five missense somatic clonal mutations that were confirmed on Sanger sequencing, including a heterozygous mutation in BRAF that results in the BRAF V600E variant protein. Since BRAF V600E is oncogenic in other tumors, further analyses were focused on this genetic lesion. The same BRAF mutation was noted in all the other 47 patients with HCL who were evaluated by means of Sanger sequencing. None of the 195 patients with other peripheral B-cell lymphomas or leukemias who were evaluated carried the BRAF V600E variant, including 38 patients with splenic marginal-zone lymphomas or unclassifiable splenic lymphomas or leukemias. In immunohistologic and Western blot studies, HCL cells expressed phosphorylated MEK and ERK (the downstream targets of the BRAF kinase), indicating a constitutive activation of the RAF-MEK-ERK mitogen-activated protein kinase pathway in HCL. In vitro incubation of BRAF-mutated primary leukemic hairy cells from 5 patients with PLX-4720, a specific inhibitor of active BRAF, led to a marked decrease in phosphorylated ERK and MEK. CONCLUSIONS; The BRAF V600E mutation was present in all patients with HCL who were evaluated. This finding may have implications for the pathogenesis, diagnosis, and targeted therapy of HCL. (Funded by Associazione Italiana per la Ricerca sul Cancro and others.).},
langid = {english},
pmcid = {PMC3689585},
keywords = {Adult,Aged,Extracellular Signal-Regulated MAP Kinases,Female,Humans,Leukemia Hairy Cell,Lymphoma B-Cell,Male,MAP Kinase Kinase Kinases,Middle Aged,Mutation,Proto-Oncogene Proteins B-raf,Sequence Analysis DNA}
}
@article{tiacciPervasiveMutationsJAKSTAT2018,
title = {Pervasive Mutations of {{JAK-STAT}} Pathway Genes in Classical {{Hodgkin}} Lymphoma},
author = {Tiacci, Enrico and Ladewig, Erik and Schiavoni, Gianluca and Penson, Alex and Fortini, Elisabetta and Pettirossi, Valentina and Wang, Yuchun and Rosseto, Ariele and Venanzi, Alessandra and Vlasevska, Sofija and Pacini, Roberta and Piattoni, Simonetta and Tabarrini, Alessia and Pucciarini, Alessandra and Bigerna, Barbara and Santi, Alessia and Gianni, Alessandro M. and Viviani, Simonetta and Cabras, Antonello and Ascani, Stefano and Crescenzi, Barbara and Mecucci, Cristina and Pasqualucci, Laura and Rabadan, Raul and Falini, Brunangelo},
date = {2018-05-31},
journaltitle = {Blood},
shortjournal = {Blood},
volume = {131},
number = {22},
eprint = {29650799},
eprinttype = {pmid},
pages = {2454--2465},
issn = {1528-0020},
doi = {10.1182/blood-2017-11-814913},
abstract = {Dissecting the pathogenesis of classical Hodgkin lymphoma (cHL), a common cancer in young adults, remains challenging because of the rarity of tumor cells in involved tissues (usually {$<$}5\%). Here, we analyzed the coding genome of cHL by microdissecting tumor and normal cells from 34 patient biopsies for a total of ∼50\,000 singly isolated lymphoma cells. We uncovered several recurrently mutated genes, namely, STAT6 (32\% of cases), GNA13 (24\%), XPO1 (18\%), and ITPKB (16\%), and document the functional role of mutant STAT6 in sustaining tumor cell viability. Mutations of STAT6 genetically and functionally cooperated with disruption of SOCS1, a JAK-STAT pathway inhibitor, to promote cHL growth. Overall, 87\% of cases showed dysregulation of the JAK-STAT pathway by genetic alterations in multiple genes (also including STAT3, STAT5B, JAK1, JAK2, and PTPN1), attesting to the pivotal role of this pathway in cHL pathogenesis and highlighting its potential as a new therapeutic target in this disease.},
langid = {english},
pmcid = {PMC6634958},
keywords = {Cell Line Tumor,DNA Mutational Analysis,Gene Expression Regulation Neoplastic,Hodgkin Disease,Humans,Janus Kinases,Mutation,Signal Transduction,STAT Transcription Factors}
}
@article{tillyPolatuzumabVedotinPreviously2022,
title = {Polatuzumab {{Vedotin}} in {{Previously Untreated Diffuse Large B-Cell Lymphoma}}},
author = {Tilly, Hervé and Morschhauser, Franck and Sehn, Laurie H. and Friedberg, Jonathan W. and Trněný, Marek and Sharman, Jeff P. and Herbaux, Charles and Burke, John M. and Matasar, Matthew and Rai, Shinya and Izutsu, Koji and Mehta-Shah, Neha and Oberic, Lucie and Chauchet, Adrien and Jurczak, Wojciech and Song, Yuqin and Greil, Richard and Mykhalska, Larysa and Bergua-Burgués, Juan M. and Cheung, Matthew C. and Pinto, Antonio and Shin, Ho-Jin and Hapgood, Greg and Munhoz, Eduardo and Abrisqueta, Pau and Gau, Jyh-Pyng and Hirata, Jamie and Jiang, Yanwen and Yan, Mark and Lee, Calvin and Flowers, Christopher R. and Salles, Gilles},
date = {2022-01-27},
journaltitle = {The New England Journal of Medicine},
shortjournal = {N Engl J Med},
volume = {386},
number = {4},
eprint = {34904799},
eprinttype = {pmid},
pages = {351--363},
issn = {1533-4406},
doi = {10.1056/NEJMoa2115304},
abstract = {BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is typically treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). However, only 60\% of patients are cured with R-CHOP. Polatuzumab vedotin is an antibody-drug conjugate targeting CD79b, which is ubiquitously expressed on the surface of malignant B cells. METHODS: We conducted a double-blind, placebo-controlled, international phase 3 trial to evaluate a modified regimen of R-CHOP (pola-R-CHP), in which vincristine was replaced with polatuzumab vedotin, as compared with standard R-CHOP, in patients with previously untreated intermediate-risk or high-risk DLBCL. Patients 18 to 80 years of age were randomly assigned in a 1:1 ratio to receive six cycles of either pola-R-CHP or R-CHOP, plus two cycles of rituximab alone. The primary end point was investigator-assessed progression-free survival. Secondary end points included overall survival and safety. RESULTS: Overall, 879 patients underwent randomization: 440 were assigned to the pola-R-CHP group and 439 to the R-CHOP group. After a median follow-up of 28.2 months, the percentage of patients surviving without progression was significantly higher in the pola-R-CHP group than in the R-CHOP group (76.7\% [95\% confidence interval (CI), 72.7 to 80.8] vs. 70.2\% [95\% CI, 65.8 to 74.6] at 2 years; stratified hazard ratio for progression, relapse, or death, 0.73 by Cox regression; 95\% CI, 0.57 to 0.95; P\,=\,0.02). Overall survival at 2 years did not differ significantly between the groups (88.7\% [95\% CI, 85.7 to 91.6] in the pola-R-CHP group and 88.6\% [95\% CI, 85.6 to 91.6] in the R-CHOP group; hazard ratio for death, 0.94; 95\% CI, 0.65 to 1.37; P\,=\,0.75). The safety profile was similar in the two groups. CONCLUSIONS: Among patients with previously untreated intermediate-risk or high-risk DLBCL, the risk of disease progression, relapse, or death was lower among those who received pola-R-CHP than among those who received R-CHOP. (Funded by F. Hoffmann-La Roche/Genentech; POLARIX ClinicalTrials.gov number, NCT03274492.).},
langid = {english},
keywords = {Adult,Aged,Antibodies Monoclonal,Antineoplastic Combined Chemotherapy Protocols,Cyclophosphamide,Double-Blind Method,Doxorubicin,Female,Humans,Immunoconjugates,Lymphoma Large B-Cell Diffuse,Male,Middle Aged,Prednisone,Progression-Free Survival,Rituximab,Vincristine}
}
@article{tohStretchyBinaryClassification2018,
title = {Stretchy Binary Classification},
author = {Toh, Kar-Ann and Lin, Zhiping and Sun, Lei and Li, Zhengguo},
date = {2018-01},
journaltitle = {Neural Networks: The Official Journal of the International Neural Network Society},
shortjournal = {Neural Netw},
volume = {97},
eprint = {29096204},
eprinttype = {pmid},
pages = {74--91},
issn = {1879-2782},
doi = {10.1016/j.neunet.2017.09.015},
abstract = {In this article, we introduce an analytic formulation for compressive binary classification. The formulation seeks to solve the least ℓp-norm of the parameter vector subject to a classification error constraint. An analytic and stretchable estimation is conjectured where the estimation can be viewed as an extension of the pseudoinverse with left and right constructions. Our variance analysis indicates that the estimation based on the left pseudoinverse is unbiased and the estimation based on the right pseudoinverse is biased. Sparseness can be obtained for the biased estimation under certain mild conditions. The proposed estimation is investigated numerically using both synthetic and real-world data.},
langid = {english},
keywords = {Algorithms,Arabidopsis,Benchmarking,Breast Neoplasms,Classification,Computer Simulation,Data Compression,Databases Genetic,Female,Fuzzy Logic,Gene Expression,Humans,Leukemia,Linear Models,Parameter learning,Pattern classification,Pattern Recognition Automated,Reproducibility of Results,Sparse estimation,User-Computer Interface}
}
@article{totzkeNovelMemberIkappaB2006,
title = {A Novel Member of the {{IkappaB}} Family, Human {{IkappaB-zeta}}, Inhibits Transactivation of P65 and Its {{DNA}} Binding.},
author = {Totzke, Gudrun and Essmann, Frank and Pohlmann, Stephan and Lindenblatt, Charlotte and Jänicke, Reiner U and Schulze-Osthoff, Klaus},
date = {2006-05},
journaltitle = {J Biol Chem},
volume = {281},
number = {18},
pages = {12645--12654}
}
@article{trinhAnalysisFOXO1Mutations,
title = {Analysis of {{FOXO1}} Mutations in Diffuse Large {{B-cell}} Lymphoma.},
author = {Trinh, Diane L and Scott, David W and Morin, Ryan D and Mendez-Lago, Maria and An, Jianghong and Jones, Steven J M and Mungall, Andrew J and Zhao, Yongjun and Schein, Jacqueline and Steidl, Christian and Connors, Joseph M and Gascoyne, Randy D and Marra, Marco A},
journaltitle = {Blood},
volume = {121},
number = {18},
year = {2013},
pages = {3666--3674},
pmcid = {PMC3643765}
}
@article{troenNOTCH2MutationsMarginal2008,
title = {{{NOTCH2}} Mutations in Marginal Zone Lymphoma},
author = {Trøen, Gunhild and Wlodarska, Iwona and Warsame, Abdirashid and Hernández Llodrà, Silvia and De Wolf-Peeters, Christiane and Delabie, Jan},
date = {2008-07},
journaltitle = {Haematologica},
shortjournal = {Haematologica},
volume = {93},
number = {7},
eprint = {18508802},
eprinttype = {pmid},
pages = {1107--1109},
issn = {1592-8721},
doi = {10.3324/haematol.11635},
langid = {english},
keywords = {B-Lymphocytes,Base Sequence,Dimerization,DNA Complementary,Gene Deletion,Gene Expression Regulation Neoplastic,Humans,In Situ Hybridization Fluorescence,Ligands,Lymphoma B-Cell Marginal Zone,Molecular Sequence Data,Mutation,Protein Structure Tertiary,Receptor Notch2,Sequence Analysis DNA}
}
@article{turunenHnRNPH1H2U12013,
title = {{{HnRNPH1}}/{{H2}}, {{U1 snRNP}}, and {{U11 snRNP}} Cooperate to Regulate the Stability of the {{U11-48K}} Pre-{{mRNA}}},
author = {Turunen, Janne J. and Verma, Bhupendra and Nyman, Tuula A. and Frilander, Mikko J.},
date = {2013-03},
journaltitle = {RNA (New York, N.Y.)},
shortjournal = {RNA},
volume = {19},
number = {3},
eprint = {23335637},
eprinttype = {pmid},
pages = {380--389},
issn = {1469-9001},
doi = {10.1261/rna.036715.112},
abstract = {Alternative splicing (AS) is a major contributor to proteome diversity, but it also regulates gene expression by introducing premature termination codons (PTCs) that destabilize transcripts, typically via the nonsense-mediated decay (NMD) pathway. Such AS events often take place within long, conserved sequence elements, particularly in genes encoding various RNA binding proteins. AS-NMD is often activated by the protein encoded by the same gene, leading to a self-regulating feedback loop that maintains constant protein levels. However, cross-regulation between different RNA binding proteins is also common, giving rise to finely tuned regulatory networks. Recently, we described a feedback mechanism regulating two protein components of the U12-dependent spliceosome (U11-48K and U11/U12-65K) through a highly conserved sequence element. These elements contain a U11 snRNP-binding splicing enhancer (USSE), which, through the U11 snRNP, activates an upstream U2-type 3'ss, resulting in the degradation of the U11-48K mRNA by AS-NMD. Through phylogenetic analysis, we now identify a G-rich sequence element that is conserved in fishes as well as mammals. We show that this element binds hnRNPF/H proteins in vitro. Knockdown of hnRNPH1/H2 or mutations in the G-run both lead to enhanced activation of the 3'ss in vivo, suggesting that hnRNPH1/H2 proteins counteract the 3'ss activation. Furthermore, we provide evidence that U1 binding immediately downstream from the G-run similarly counteracts the U11-mediated activation of the alternative 3'ss. Thus, our results elucidate the mechanism in which snRNPs from both spliceosomes together with hnRNPH1/H2 proteins regulate the recognition and activation of the highly conserved alternative splice sites within the U11-48K pre-mRNA.},
langid = {english},
pmcid = {PMC3677248},
keywords = {Amino Acid Sequence,Animals,Binding Sites,HEK293 Cells,HeLa Cells,Humans,Ribonucleoprotein U1 Small Nuclear,Ribonucleoproteins Small Nuclear,RNA Heterogeneous Nuclear,RNA Precursors,RNA Splicing,RNA Stability,Spliceosomes}
}
@article{tzankovPrognosticImmunophenotypicBiomarker2010,
title = {Prognostic Immunophenotypic Biomarker Studies in Diffuse Large {{B}} Cell Lymphoma with Special Emphasis on Rational Determination of Cut-off Scores.},
author = {Tzankov, Alexandar and Zlobec, Inti and Went, Philip and Robl, Hannes and Hoeller, Sylvia and Dirnhofer, Stephan},
date = {2010-02},
journaltitle = {Leuk lymphoma},
volume = {51},
number = {2},
pages = {199--212}
}
@article{ullrichDynamicChangesIntron2020,
title = {Dynamic Changes in Intron Retention Are Tightly Associated with Regulation of Splicing Factors and Proliferative Activity during {{B-cell}} Development},
author = {Ullrich, Sebastian and Guigó, Roderic},
date = {2020-02-20},
journaltitle = {Nucleic Acids Research},
shortjournal = {Nucleic Acids Research},
volume = {48},
number = {3},
pages = {1327--1340},
issn = {0305-1048},
doi = {10.1093/nar/gkz1180},
url = {https://doi.org/10.1093/nar/gkz1180},
urldate = {2022-10-03},
abstract = {Intron retention (IR) has been proposed to modulate the delay between transcription and translation. Here, we provide an exhaustive characterization of IR in differentiated white blood cells from both the myeloid and lymphoid lineage where we observed highest levels of IR in monocytes and B-cells, in addition to previously reported granulocytes. During B-cell differentiation, we found an increase in IR from the bone marrow precursors to cells residing in secondary lymphoid organs. B-cells that undergo affinity maturation to become antibody producing plasma cells steadily decrease retention. In general, we found an inverse relationship between global IR levels and both the proliferative state of cells, and the global levels of expression of splicing factors. IR dynamics during B-cell differentiation appear to be conserved between human and mouse, suggesting that IR plays an important biological role, evolutionary conserved, during blood cell differentiation. By correlating the expression of non-core splicing factors with global IR levels, and analyzing RNA binding protein knockdown and eCLIP data, we identify a few splicing factors likely playing an evolutionary conserved role in IR regulation. Our work provides new insights into the role of IR during hematopoiesis, and on the main factors involved in regulating IR.}
}
@article{urenHighthroughputAnalysesHnRNP2016,
title = {High-Throughput Analyses of {{hnRNP H1}} Dissects Its Multi-Functional Aspect},
author = {Uren, Philip J. and Bahrami-Samani, Emad and family=Araujo, given=Patricia Rosa, prefix=de, useprefix=true and Vogel, Christine and Qiao, Mei and Burns, Suzanne C. and Smith, Andrew D. and Penalva, Luiz O. F.},
date = {2016},
journaltitle = {RNA biology},
shortjournal = {RNA Biol},
volume = {13},
number = {4},
eprint = {26760575},
eprinttype = {pmid},
pages = {400--411},
issn = {1555-8584},
doi = {10.1080/15476286.2015.1138030},
abstract = {hnRNPs are polyvalent RNA binding proteins that have been implicated in a range of regulatory roles including splicing, mRNA decay, translation, and miRNA metabolism. A variety of genome wide studies have taken advantage of methods like CLIP and RIP to identify the targets and binding sites of RNA binding proteins. However, due to the complex nature of RNA-binding proteins, these studies are incomplete without assays that characterize the impact of RBP binding on mRNA target expression. Here we used a suite of high-throughput approaches (RIP-Seq, iCLIP, RNA-Seq and shotgun proteomics) to provide a comprehensive view of hnRNP H1s ensemble of targets and its role in splicing, mRNA decay, and translation. The combination of RIP-Seq and iCLIP allowed us to identify a set of 1,086 high confidence target transcripts. Binding site motif analysis of these targets suggests the TGGG tetramer as a prevalent component of hnRNP H1 binding motif, with particular enrichment around intronic hnRNP H1 sites. Our analysis of the target transcripts and binding sites indicates that hnRNP H1s involvement in splicing is 2-fold: it directly affects a substantial number of splicing events, but also regulates the expression of major components of the splicing machinery and other RBPs with known roles in splicing regulation. The identified mRNA targets displayed function enrichment in MAPK signaling and ubiquitin mediated proteolysis, which might be main routes by which hnRNP H1 promotes tumorigenesis.},
langid = {english},
pmcid = {PMC4841607},
keywords = {Binding Sites,HeLa Cells,Heterogeneous-Nuclear Ribonucleoprotein Group F-H,High-Throughput Nucleotide Sequencing,hnRNP H1,Humans,iCLIP,Integrated analysis,Proteomics,RIP-seq,RNA Splicing,RNA-binding proteins,RNA-seq}
}
@article{urenSiteIdentificationHighthroughput2012,
title = {Site Identification in High-Throughput {{RNA-protein}} Interaction Data},
author = {Uren, Philip J. and Bahrami-Samani, Emad and Burns, Suzanne C. and Qiao, Mei and Karginov, Fedor V. and Hodges, Emily and Hannon, Gregory J. and Sanford, Jeremy R. and Penalva, Luiz O. F. and Smith, Andrew D.},
date = {2012-12-01},
journaltitle = {Bioinformatics (Oxford, England)},
shortjournal = {Bioinformatics},
volume = {28},
number = {23},
eprint = {23024010},
eprinttype = {pmid},
pages = {3013--3020},
issn = {1367-4811},
doi = {10.1093/bioinformatics/bts569},
abstract = {MOTIVATION: Post-transcriptional and co-transcriptional regulation is a crucial link between genotype and phenotype. The central players are the RNA-binding proteins, and experimental technologies [such as cross-linking with immunoprecipitation- (CLIP-) and RIP-seq] for probing their activities have advanced rapidly over the course of the past decade. Statistically robust, flexible computational methods for binding site identification from high-throughput immunoprecipitation assays are largely lacking however. RESULTS: We introduce a method for site identification which provides four key advantages over previous methods: (i) it can be applied on all variations of CLIP and RIP-seq technologies, (ii) it accurately models the underlying read-count distributions, (iii) it allows external covariates, such as transcript abundance (which we demonstrate is highly correlated with read count) to inform the site identification process and (iv) it allows for direct comparison of site usage across cell types or conditions. AVAILABILITY AND IMPLEMENTATION: We have implemented our method in a software tool called Piranha. Source code and binaries, licensed under the GNU General Public License (version 3) are freely available for download from http://smithlab.usc.edu. CONTACT: andrewds@usc.edu SUPPLEMENTARY INFORMATION: Supplementary data available at Bioinformatics online.},
langid = {english},
pmcid = {PMC3509493},
keywords = {Base Sequence,Binding Sites,Computational Biology,HEK293 Cells,HeLa Cells,High-Throughput Nucleotide Sequencing,Humans,RNA,RNA-Binding Proteins,Sequence Analysis RNA,Software}
}
@article{vaandragerRecombinasemediatedTranspositionBCL2gene2000,
title = {V({{D}}){{J}} Recombinase-Mediated Transposition of the {{BCL2gene}} to the {{IGH}} Locus in Follicular Lymphoma},
author = {Vaandrager, Jan-Willem and Schuuring, Ed and Philippo, Katja and Kluin, Philip M.},
date = {2000-09-01},
journaltitle = {Blood},
shortjournal = {Blood},
volume = {96},
number = {5},
pages = {1947--1952},
issn = {0006-4971},
doi = {10.1182/blood.V96.5.1947},
url = {https://www.sciencedirect.com/science/article/pii/S0006497120544753},
urldate = {2023-10-17},
abstract = {Using DNA fiber fluorescence in-situ hybridization (FISH) and 3-color interphase FISH, 2 cases of follicular lymphoma were identified in which the BCL2 gene was excised from 18q21 and inserted into the immunoglobulin heavy chain (IGH) locus at 14q32. Both the insertion breakpoint at 14q32 and the deletion breakpoint at 18q21 were cloned using inverse polymerase chain reaction. Sequence analysis showed that the JH sequences were juxtaposed to the 5′-side of BCL2, and the DH sequences were juxtaposed to the 3′-side of BCL2. There were breakpoints at both the JH and DH recombination signal sequences, and N-nucleotides were present at all breakpoint junctions. At theBCL2 locus, the 3′-breakpoints in both cases were localized at exactly the same nucleotide position, 6.2 kilobase downstream of the major breakpoint region, directly adjacent to a complete cryptic recombination signal sequence (RSS) consisting of a heptamer, a nonamer, and a 23–base pair (bp) spacer. The BCL25′-breakpoints were approximately 600 bp upstream of the gene, within the CA repeats. Although less evident than for the BCL23′-breakpoints, cryptic RSSs were also identified at these breakpoints, with a 12-bp spacer. On the basis of structural characteristics of these rearrangements, a model is proposed in which the BCL2 gene is deleted from its locus by recombination activation gene-1/-2 (RAG-1/-2)–mediated excision. The gene is subsequently inserted into the recombiningIGH locus, a process involving the formation of hybrid joints between the IGH coding ends and theBCL2 signal ends.}
}
@article{valliClassificationCanineMalignant2011,
title = {Classification of {{Canine Malignant Lymphomas According}} to the {{World Health Organization Criteria}}},
author = {Valli, V. E. and Myint, M. San and Barthel, A. and Bienzle, D. and Caswell, J. and Colbatzky, F. and Durham, A. and Ehrhart, E. J. and Johnson, Y. and Jones, C. and Kiupel, M. and Labelle, P. and Lester, S. and Miller, M. and Moore, P. and Moroff, S. and Roccabianca, P. and Ramos-Vara, J. and Ross, A. and Scase, T. and Tvedten, H. and Vernau, W.},
date = {2011-01-01},
journaltitle = {Veterinary Pathology},
shortjournal = {Vet Pathol},
volume = {48},
number = {1},
pages = {198--211},
publisher = {SAGE Publications Inc},
issn = {0300-9858},
doi = {10.1177/0300985810379428},
url = {https://doi.org/10.1177/0300985810379428},
urldate = {2021-05-13},
abstract = {A study was carried out to test the accuracy and consistency of veterinary pathologists, not specialists in hematopathology, in applying the World Health Organization (WHO) system of classification of canine lymphomas. This study represents an initiative of the ACVP Oncology Committee, and the classification has been endorsed by the World Small Animal Veterinary Association (WASVA). Tissue biopsies from cases of canine lymphoma were received from veterinary oncologists, and a study by pathologists given only signalment was carried out on 300 cases. Twenty pathologists reviewed these 300 cases with each required to choose a diagnosis from a list of 43 B and T cell lymphomas. Three of the 20 were hematopathologists who determined the consensus diagnosis for each case. The 17 who formed the test group were experienced but not specialists in hematopathology, and most were diplomates of the American or European Colleges of Veterinary Pathology. The overall accuracy of the 17 pathologists on the 300 cases was 83\%. When the analysis was limited to the 6 most common diagnoses, containing 80\% of all cases, accuracy rose to 87\%. In a test of reproducibility enabled by reintroducing 5\% of cases entered under a different identity, the overall agreement between the first and second diagnosis ranged from 40 to 87\%. The statistical review included 43,000 data points for each of the 20 pathologists.},
langid = {english},
keywords = {Animals,dog,Dog Diseases,Dogs,Lymph Nodes,Lymphoma,Observer Variation,oncology,Pathology Veterinary,Veterinarians,World Health Organization}
}
@article{valloisActivatingMutationsGenes2016,
title = {Activating Mutations in Genes Related to {{TCR}} Signaling in Angioimmunoblastic and Other Follicular Helper {{T-cell}}–Derived Lymphomas},
author = {Vallois, David and Dobay, Maria Pamela D. and Morin, Ryan D. and Lemonnier, François and Missiaglia, Edoardo and Juilland, Mélanie and Iwaszkiewicz, Justyna and Fataccioli, Virginie and Bisig, Bettina and Roberti, Annalisa and Grewal, Jasleen and Bruneau, Julie and Fabiani, Bettina and Martin, Antoine and Bonnet, Christophe and Michielin, Olivier and Jais, Jean-Philippe and Figeac, Martin and Bernard, Olivier A. and Delorenzi, Mauro and Haioun, Corinne and Tournilhac, Olivier and Thome, Margot and Gascoyne, Randy D. and Gaulard, Philippe and De Leval, Laurence},
date = {2016-09-15},
journaltitle = {Blood},
volume = {128},
number = {11},
pages = {1490--1502},
issn = {0006-4971, 1528-0020},
doi = {10.1182/blood-2016-02-698977},
url = {https://ashpublications.org/blood/article/128/11/1490/35240/Activating-mutations-in-genes-related-to-TCR},
urldate = {2023-10-26},
abstract = {Key Points A high frequency of diverse activating mutations in costimulatory/TCR-related signaling genes occurs in AITL and other TFH-derived PTCL. Deregulated TCR activation may play a role in the pathogenesis of TFH-derived PTCL, paving the way for developing novel targeted therapies.},
langid = {english}
}
@article{vandenbrandRecurrentMutationsGenes2017,
title = {Recurrent Mutations in Genes Involved in Nuclear Factor-{{κB}} Signalling in Nodal Marginal Zone Lymphoma-Diagnostic and Therapeutic Implications},
author = {family=Brand, given=Michiel, prefix=van den, useprefix=true and Rijntjes, Jos and Hebeda, Konnie M. and Menting, Laura and Bregitha, Carolyn V. and Stevens, Wendy B. C. and family=Velden, given=Walter J. F. M., prefix=van der, useprefix=true and Tops, Bastiaan B. J. and family=Krieken, given=J. Han J. M., prefix=van, useprefix=true and Groenen, Patricia J. T. A.},
date = {2017-01},
journaltitle = {Histopathology},
shortjournal = {Histopathology},
volume = {70},
number = {2},
eprint = {27297871},
eprinttype = {pmid},
pages = {174--184},
issn = {1365-2559},
doi = {10.1111/his.13015},
abstract = {AIMS: To investigate the spectrum of mutations in 20 genes involved in B-cell receptor and/or Toll-like receptor signalling resulting in activation of nuclear factor-κB (NF-κB) in 20 nodal marginal zone lymphomas (NMZLs), 20 follicular lymphomas (FLs), and 11 cases of B-cell lymphoma, unclassifiable (BCL-u). METHODS AND RESULTS: Nodal marginal zone lymphomas were diagnosed according to strict criteria, including the expression of at least one putative marginal zone marker (MNDA and/or IRTA1). Cases that showed features of NMZL but did not fulfil all criteria were included as BCL-u. All FLs were required to have a BCL2 rearrangement. Mutations were found in: nine NMZLs, with recurrent mutations in TNFAIP3 and CD79B; 12 FLs, with recurrent mutations in TNFRSF14, TNFAIP3, and CARD11; and five cases of BCL-u, with recurrent mutations in TNFRSF14. TNFRSF14 mutations were present in FL and BCL-u, but not in any of the NMZLs. In the BCL-u group, TNFRSF14 mutations clustered with a FL immunophenotype. CONCLUSIONS: These results suggest that TNFRSF14 mutations point towards a diagnosis of FL, and can be used in the sometimes difficult distinction between NMZL and FL, but to apply this in diagnostics would require confirmation in an independent cohort. In addition, the presence or absence of specific mutations in pathways converging on NF-κB could be important for decisions regarding targeted treatment.},
langid = {english},
keywords = {Aged,Biomarkers Tumor,diagnosis,Diagnosis Differential,Disease-Free Survival,Female,follicular lymphoma,High-Throughput Nucleotide Sequencing,Humans,Immunohistochemistry,Kaplan-Meier Estimate,Lymphoma B-Cell Marginal Zone,Lymphoma Follicular,Male,Middle Aged,Mutation,NF-kappa B,nodal marginal zone lymphoma,non-Hodgkin lymphoma,nuclear factor-κB,Receptors Tumor Necrosis Factor Member 14,Signal Transduction,TNFAIP3,TNFRSF14}
}
@article{vaughanInhibitoryFcgRIIbCD32b2014,
title = {Inhibitory {{FcγRIIb}} ({{CD32b}}) Becomes Activated by Therapeutic {{mAb}} in Both Cis and Trans and Drives Internalization According to Antibody Specificity},
author = {Vaughan, Andrew T and Iriyama, Chisako and Beers, Stephen A and Chan, Claude H T and Lim, Sean H and Williams, Emily L and Shah, Vallari and Roghanian, Ali and Frendéus, Bjorn and Glennie, Martin J and Cragg, Mark S},
date = {2014-01},
journaltitle = {Blood},
volume = {123},
number = {5},
pages = {669--677}
}
@article{veisBcl2deficientMiceDemonstrate1993,
title = {Bcl-2-Deficient Mice Demonstrate Fulminant Lymphoid Apoptosis, Polycystic Kidneys, and Hypopigmented Hair},
author = {Veis, Deborah J. and Sorenson, Christine M. and Shutter, John R. and Korsmeyer, Stanley J.},
date = {1993-10-22},
journaltitle = {Cell},
shortjournal = {Cell},
volume = {75},
number = {2},
pages = {229--240},
issn = {0092-8674},
doi = {10.1016/0092-8674(93)80065-M},
url = {https://www.sciencedirect.com/science/article/pii/009286749380065M},
urldate = {2022-10-06},
abstract = {bcl-2 —/— mice complete embryonic development, but display growth retardation and early mortality postnatally. Hematopoiesis including lymphocyte differentiation is initially normal, but thymus and spleen undergo massive apoptotic involution. Thymocytes require an apoptotic signal to manifest accelerated cell death. Renal failure results from severe polycystic kidney disease characterized by dilated proximal and distal tubular segments and hyperproliferation of epithelium and interstitium. bcl-2 —/— mice turn gray with the second hair follicle cycle, implicating a defect in redox-regulated melanin synthesis. The abnormalities in these loss of function mice argue that Bcl-2 is a death repressor molecule functioning in an antioxidant pathway.},
langid = {english}
}
@article{vela-chavezCyclinD1Positive2011,
title = {Cyclin {{D1}} Positive Diffuse Large {{B-cell}} Lymphoma Is a Post-Germinal Center-Type Lymphoma without Alterations in the {{CCND1}} Gene Locus.},
author = {Vela-Chávez, Teresa and Adam, Patrick and Kremer, Marcus and Bink, Karin and Bacon, Christopher M and Menon, Geetha and Ferry, Judith A and Fend, Falko and Jaffe, Elaine S and Quintanilla-Martínez, Leticia},
date = {2011-03},
journaltitle = {Leuk lymphoma},
volume = {52},
number = {3},
pages = {458--466}
}
@article{venablesMultipleSpecificMRNA2008,
title = {Multiple and {{Specific mRNA Processing Targets}} for the {{Major Human hnRNP Proteins}}},
author = {Venables, Julian P. and Koh, Chu-Shin and Froehlich, Ulrike and Lapointe, Elvy and Couture, Sonia and Inkel, Lyna and Bramard, Anne and Paquet, Éric R. and Watier, Valérie and Durand, Mathieu and Lucier, Jean-François and Gervais-Bird, Julien and Tremblay, Karine and Prinos, Panagiotis and Klinck, Roscoe and Elela, Sherif Abou and Chabot, Benoit},
date = {2008-10},
journaltitle = {Molecular and Cellular Biology},
volume = {28},
number = {19},
pages = {6033--6043},
publisher = {American Society for Microbiology},
doi = {10.1128/MCB.00726-08},
url = {https://journals.asm.org/doi/full/10.1128/MCB.00726-08},
urldate = {2022-09-27}
}
@article{venkataramananDDX3XDDX3YAre2021,
title = {{{DDX3X}} and {{DDX3Y}} Are Redundant in Protein Synthesis},
author = {Venkataramanan, Srivats and Gadek, Margaret and Calviello, Lorenzo and Wilkins, Kevin and Floor, Stephen},
date = {2021-09-17},
journaltitle = {RNA},
shortjournal = {RNA},
eprint = {34535544},
eprinttype = {pmid},
pages = {rna.078926.121},
publisher = {Cold Spring Harbor Lab},
issn = {1355-8382, 1469-9001},
doi = {10.1261/rna.078926.121},
url = {http://rnajournal.cshlp.org/content/early/2021/09/17/rna.078926.121},
urldate = {2021-09-23},
abstract = {DDX3 is a DEAD-box RNA helicase that regulates translation and is encoded by the X- and Y-linked paralogs DDX3X and DDX3Y. While DDX3X is ubiquitously expressed in human tissues and essential for viability, DDX3Y is male-specific and shows lower and more variable expression than DDX3X in somatic tissues. Heterozygous genetic lesions in DDX3X mediate a class of developmental disorders called DDX3X syndrome, while loss of DDX3Y is implicated in male infertility. One possible explanation for female-bias in DDX3X syndrome is that DDX3Y encodes a polypeptide with different biochemical activity. In this study, we use ribosome profiling and in vitro translation to demonstrate that the X- and Y-linked paralogs of DDX3 play functionally redundant roles in translation. We find that transcripts that are sensitive to DDX3X depletion or mutation are rescued by complementation with DDX3Y. Our data indicate that DDX3X and DDX3Y proteins can functionally complement each other in the context of mRNA translation in human cells. DDX3Y is not expressed in a large fraction of the central nervous system. These findings suggest that expression differences, not differences in paralog-dependent protein synthesis, underlie the sex-bias of DDX3X-associated diseases.},
langid = {english},
keywords = {DEAD-box proteins,RNA,sex differences,translational control}
}
@article{veraldiHnRNPInfluencesBinding2001,
title = {{{hnRNP F Influences Binding}} of a 64-{{Kilodalton Subunit}} of {{Cleavage Stimulation Factor}} to {{mRNA Precursors}} in {{Mouse B Cells}}},
author = {Veraldi, Kristen L. and Arhin, George K. and Martincic, Kathleen and Chung-Ganster, Ling-Hsiu and Wilusz, Jeffrey and Milcarek, Christine},
date = {2001-02-15},
journaltitle = {Molecular and Cellular Biology},
volume = {21},
number = {4},
pages = {1228--1238},
publisher = {American Society for Microbiology},
doi = {10.1128/MCB.21.4.1228-1238.2001},
url = {https://journals.asm.org/doi/full/10.1128/MCB.21.4.1228-1238.2001},
urldate = {2022-10-03}
}
@article{viganoSomaticIL4RMutations2018,
title = {Somatic {{IL4R}} Mutations in Primary Mediastinal Large {{B-cell}} Lymphoma Lead to Constitutive {{JAK-STAT}} Signaling Activation},
author = {Viganò, Elena and Gunawardana, Jay and Mottok, Anja and Van Tol, Tessa and Mak, Katina and Chan, Fong Chun and Chong, Lauren and Chavez, Elizabeth and Woolcock, Bruce and Takata, Katsuyoshi and Twa, David and Shulha, Hennady P. and Telenius, Adèle and Kutovaya, Olga and Hung, Stacy S. and Healy, Shannon and Ben-Neriah, Susana and Leroy, Karen and Gaulard, Philippe and Diepstra, Arjan and Kridel, Robert and Savage, Kerry J. and Rimsza, Lisa and Gascoyne, Randy and Steidl, Christian},
date = {2018-05-03},
journaltitle = {Blood},
shortjournal = {Blood},
volume = {131},
number = {18},
eprint = {29467182},
eprinttype = {pmid},
pages = {2036--2046},
issn = {1528-0020},
doi = {10.1182/blood-2017-09-808907},
abstract = {Primary mediastinal large B-cell lymphoma (PMBCL) is a distinct subtype of diffuse large B-cell lymphoma thought to arise from thymic medullary B cells. Gene mutations underlying the molecular pathogenesis of the disease are incompletely characterized. Here, we describe novel somatic IL4R mutations in 15 of 62 primary cases of PMBCL (24.2\%) and in all PMBCL-derived cell lines tested. The majority of mutations (11/21; 52\%) were hotspot single nucleotide variants in exon 8, leading to an I242N amino acid change in the transmembrane domain. Functional analyses establish this mutation as gain of function leading to constitutive activation of the JAK-STAT pathway and upregulation of downstream cytokine expression profiles and B cell-specific antigens. Moreover, expression of I242N mutant IL4R in a mouse xenotransplantation model conferred growth advantage in vivo. The pattern of concurrent mutations within the JAK-STAT signaling pathway suggests additive/synergistic effects of these gene mutations contributing to lymphomagenesis. Our data establish IL4R mutations as novel driver alterations and provide a strong preclinical rationale for therapeutic targeting of JAK-STAT signaling in PMBCL.},
langid = {english},
keywords = {Animals,Cell Line Tumor,Disease Models Animal,Female,Humans,Interleukin-4 Receptor alpha Subunit,Janus Kinases,Lymphoma Large B-Cell Diffuse,Mediastinal Neoplasms,Mice,Mutation,Phosphorylation,Signal Transduction,STAT Transcription Factors}
}
@article{vonhachtIdentificationCharacterizationRNA2014,
title = {Identification and Characterization of {{RNA}} Guanine-Quadruplex Binding Proteins},
author = {family=Hacht, given=Annekathrin, prefix=von, useprefix=true and Seifert, Oliver and Menger, Marcus and Schütze, Tatjana and Arora, Amit and Konthur, Zoltán and Neubauer, Peter and Wagner, Anke and Weise, Christoph and Kurreck, Jens},
date = {2014-06},
journaltitle = {Nucleic Acids Research},
shortjournal = {Nucleic Acids Res},
volume = {42},
number = {10},
eprint = {24771345},
eprinttype = {pmid},
pages = {6630--6644},
issn = {1362-4962},
doi = {10.1093/nar/gku290},
abstract = {Guanine quadruplex (G-quadruplex) motifs in the 5' untranslated region (5'-UTR) of mRNAs were recently shown to influence the efficiency of translation. In the present study, we investigate the interaction between cellular proteins and the G-quadruplexes located in two mRNAs (MMP16 and ARPC2). Formation of the G-quadruplexes was confirmed by biophysical characterization and the inhibitory activity on translation was shown by luciferase reporter assays. In experiments with whole cell extracts from different eukaryotic cell lines, G-quadruplex-binding proteins were isolated by pull-down assays and subsequently identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry. The binding partners of the RNA G-quadruplexes we discovered included several heterogeneous nuclear ribonucleoproteins, ribosomal proteins, and splicing factors, as well as other proteins that have previously not been described to interact with nucleic acids. While most of the proteins were specific for either of the investigated G-quadruplexes, some of them bound to both motifs. Selected candidate proteins were subsequently produced by recombinant expression and dissociation constants for the interaction between the proteins and RNA G-quadruplexes in the low nanomolar range were determined by surface plasmon resonance spectroscopy. The present study may thus help to increase our understanding of the mechanisms by which G-quadruplexes regulate translation.},
langid = {english},
pmcid = {PMC4041461},
keywords = {5' Untranslated Regions,Actin-Related Protein 2,G-Quadruplexes,HEK293 Cells,HeLa Cells,Humans,Matrix Metalloproteinase 16,Protein Biosynthesis,RNA-Binding Proteins}
}
@article{voseMantleCellLymphoma2017,
title = {Mantle Cell Lymphoma: 2017 Update on Diagnosis, Risk-Stratification, and Clinical Management},
shorttitle = {Mantle Cell Lymphoma},
author = {Vose, Julie M.},
date = {2017},
journaltitle = {American Journal of Hematology},
volume = {92},
number = {8},
pages = {806--813},
issn = {1096-8652},
doi = {10.1002/ajh.24797},
url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/ajh.24797},
urldate = {2019-12-21},
abstract = {Disease Overview Mantle cell lymphoma (MCL) is a non-Hodgkin lymphoma characterized by involvement of the lymph nodes, spleen, blood and bone marrow with a short remission duration to standard therapies and a median overall survival (OS) of 4-5 years. Diagnosis Diagnosis is based on lymph node, bone marrow, or tissue morphology of centrocytic lymphocytes, small cell type, or blastoid variant cells. A chromosomal translocation t (11:14) is the molecular hallmark of MCL, resulting in the overexpression of cyclin D1. Cyclin D1 is detected by immunohistochemistry in 98\% of cases. The absence of SOX-11 or a low Ki-67 may correlate with a more indolent form of MCL. The differential diagnosis of MCL includes small lymphocytic lymphoma, marginal zone lymphoma, and follicular lymphoma. Risk Stratification The MCL International Prognostic Index (MIPI) is the prognostic model most often used and incorporates ECOG performance status, age, leukocyte count, and lactic dehydrogenase. A modification of the MIPI also adds the Ki-67 proliferative index if available. The median OS for the low-risk group was not reached (5-year OS of 60\%). The median OS for the intermediate risk group was 51 months and 29 months for the high risk group. Risk-Adapted Therapy For selected indolent, low MIPI MCL patients, initial observation may be appropriate therapy. For younger patients with intermediate or high risk MIPI MCL, aggressive therapy with a cytotoxic Regimen followed by autologous stem cell transplantation should be considered. Rituximab maintenance after autologous stem cell transplantation has also improved the progression-free and overall survival. For older symptomatic MCL patients with intermediate or high risk MIPI, combination chemotherapy with R-CHOP, R-Bendamustine, or a clinical trial should be considered. In addition, rituximab maintenance therapy may prolong the progression-free survival. At the time of relapse, agents directed at activated pathways in MCL cells such as bortezomib (NFkB inhibitor), lenalidamide (anti-angiogenesis) and Ibruitinib (Bruton's Tyrosine Kinase [BTK] inhibitor) have demonstrated excellent clinical activity in MCL patients. Autologous or allogeneic stem cell transplantation can also be considered in young patients. Clinical trials with novel agents are always a consideration for MCL patients.},
langid = {english}
}
@article{wagenerCrypticInsertionMYC2019,
title = {Cryptic Insertion of {{MYC}} Exons 2 and 3 into the {{IGH}} Locus Detected by Whole Genome Sequencing in a Case of {{MYC-negative Burkitt}} Lymphoma [Published Online Ahead of Print {{May}} 2019]},
author = {Wagener, Rabea and Bens, Susanne and Toprak, Umut H. and Seufert, Julian and López, Cristina and Scholz, Ingrid and Herbrueggen, Heidi and Oschlies, Ilske and Stilgenbauer, Stephan and Schlesner, Matthias and Klapper, Wolfram and Burkhardt, Birgit and Siebert, Reiner},
date = {2019-05-09},
journaltitle = {Haematologica},
shortjournal = {Haematologica},
volume = {10.3324/haematol.2018.208140},
eprint = {31073073},
eprinttype = {pmid},
issn = {1592-8721},
doi = {10.3324/haematol.2018.208140},
langid = {english},
keywords = {Aggressive Non-Hodgkin's Lymphoma,Cytogenetics and Molecular Genetics,IG-MYC translocation}
}
@article{wagenerPCBP1GeneEncoding2015,
title = {The {{{\emph{PCBP1}}}} Gene Encoding Poly(Rc) Binding Protein i Is Recurrently Mutated in {{Burkitt}} Lymphoma: {{{\emph{PCBP1}}}} {{MUTATIONS IN BURKITT LYMPHOMA}}},
shorttitle = {The {{{\emph{PCBP1}}}} Gene Encoding Poly(Rc) Binding Protein i Is Recurrently Mutated in {{Burkitt}} Lymphoma},
author = {Wagener, Rabea and Aukema, Sietse M. and Schlesner, Matthias and Haake, Andrea and Burkhardt, Birgit and Claviez, Alexander and Drexler, Hans G. and Hummel, Michael and Kreuz, Markus and Loeffler, Markus and Rosolowski, Maciej and López, Cristina and Möller, Peter and Richter, Julia and Rohde, Marius and Betts, Matthew J. and Russell, Robert B. and Bernhart, Stephan H. and Hoffmann, Steve and Rosenstiel, Philip and Schilhabel, Markus and Szczepanowski, Monika and Trümper, Lorenz and Klapper, Wolfram and Siebert, Reiner and {on behalf of the ICGC MMML-Seq-Project and the “Molecular Mechanisms in Malignant Lymphomas” Network Project of the Deutsche Krebshilfe}},
date = {2015-09},
journaltitle = {Genes, Chromosomes and Cancer},
shortjournal = {Genes Chromosomes Cancer},
volume = {54},
number = {9},
pages = {555--564},
issn = {10452257},
doi = {10.1002/gcc.22268},
url = {https://onlinelibrary.wiley.com/doi/10.1002/gcc.22268},
urldate = {2022-09-25},
langid = {english}
}
@article{wallaceDetectionBcl2142006,
title = {Detection of the Bcl-2 t(14;18) {{Translocation}} and {{Proto-Oncogene Expression}} in {{Primary Intraocular Lymphoma}}},
author = {Wallace, Dana J. and Shen, DeFen and Reed, George F. and Miyanaga, Masaru and Mochizuki, Manabu and Sen, H. Nida and Dahr, Samuel S. and Buggage, Ronald R. and Nussenblatt, Robert B. and Chan, Chi-Chao},
date = {2006-07-01},
journaltitle = {Investigative Ophthalmology \& Visual Science},
shortjournal = {Investigative Ophthalmology \& Visual Science},
volume = {47},
number = {7},
pages = {2750--2756},
issn = {1552-5783},
doi = {10.1167/iovs.05-1312},
url = {https://doi.org/10.1167/iovs.05-1312},
urldate = {2022-10-04},
abstract = {purpose. Primary intraocular lymphoma (PIOL) is a diffuse large B cell lymphoma that initially infiltrates the retina, vitreous, or optic nerve head, with or without central nervous system involvement. This study examined the expression of the bcl-2 t(14;18) translocation, the bcl-10 gene, and high expression of bcl-6 mRNA in PIOL cells. methods. Microdissection and PCR analysis were used to examine vitreous specimens in patients with PIOL for the presence of bcl-2 t(14;18) translocations, the bcl-10 gene, and expression of bcl-6 mRNA. A medical record review was also conducted to determine whether the bcl-2 t(14;18) translocation correlated with prognosis. results. Forty of 72 (55\%) PIOL patients expressed the bcl-2 t(14;18) translocation at the major breakpoint region. Fifteen of 68 (22\%) patients expressed the translocation at the minor cluster region. The bcl-10 gene was detected in 6 of 26 (23\%) patients, whereas 4 of 4 (100\%) PIOL patients expressed higher levels of bcl-6 mRNA compared with inflammatory lymphocytes. An analysis of clinical outcome in 23 PIOL patients revealed no significant association between bcl-2 t(14;18) translocations and survival or relapse. However, patients with the translocation were significantly younger. conclusions. PIOL has unique molecular patterns of bcl-2, bcl-10, and bcl-6 when compared with other systemic lymphomas. This study lays the foundation for future studies aimed at exploring the genotypic classification of PIOL based on the quantitative molecular framework of gene expression profiling, with the goal of providing useful adjuncts to the pathologic diagnosis of this complex disease.}
}
@article{wallCellularStressOrchestrates2020,
title = {Cellular Stress Orchestrates the Localization of {{hnRNP H}} to Stress Granules},
author = {Wall, Michael L. and Bera, Amit and Wong, Florence K. and Lewis, Stephen M.},
date = {2020-09-01},
journaltitle = {Experimental Cell Research},
shortjournal = {Experimental Cell Research},
volume = {394},
number = {1},
pages = {112111},
issn = {0014-4827},
doi = {10.1016/j.yexcr.2020.112111},
url = {https://www.sciencedirect.com/science/article/pii/S0014482720303578},
urldate = {2023-01-09},
abstract = {Heterogeneous nuclear ribonucleoprotein (hnRNP) H is a member of hnRNP H/F protein subfamily of hnRNPs that regulate the maturation and post-transcriptional processing of pre-mRNA. As a component of an mRNA export complex, hnRNP H shuttles mature mRNA from the nucleus to the cytoplasm. Although hnRNP H is primarily a nuclear protein, it can accumulate in the cytoplasm in certain tissues and cell types; however, the physiological relevance of hnRNP H cytoplasmic accumulation is unknown. Here we show that under cellular stress hnRNP H accumulates in the cytoplasm and is required for efficient recovery from cellular stress. Moreover, we find that cytoplasmic hnRNP H localizes to stress granules and that the RRM3 domain of hnRNP H is necessary for this localization. Together, our results demonstrate that hnRNP H accumulates in the cytoplasm under cellular stress and is recruited to stress granules.},
langid = {english},
keywords = {Cellular stress,hnRNP H,Osmotic stress,RNA-Binding protein,Stress granule}
}
@article{wangEmergingRolesHnRNPK2020,
title = {The Emerging Roles of {{hnRNPK}}},
author = {Wang, Ziyi and Qiu, Heng and He, Jianbo and Liu, Langxia and Xue, Wei and Fox, Archa and Tickner, Jennifer and Xu, Jiake},
date = {2020},
journaltitle = {Journal of Cellular Physiology},
volume = {235},
number = {3},
pages = {1995--2008},
issn = {1097-4652},
doi = {10.1002/jcp.29186},
url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/jcp.29186},
urldate = {2022-09-22},
abstract = {Heterogeneous nuclear ribonucleoprotein K (hnRNPK) is an DNA/RNA-binding protein and regulates a wide range of biological processes and disease pathogenesis. It contains 3 K-homologous (KH) domains, which are conserved in other RNA-binding proteins, mediate nucleic acid binding activity, and function as an enhancer or repressor of gene transcription. Phosphorylation of the protein alters its regulatory function, which also enables the protein to serve as a docking platform for the signal transduction proteins. In terms of the function of hnRNPK, it is central to many cellular events, including long noncoding RNA (lncRNA) regulation, cancer development and bone homoeostasis. Many studies have identified hnRNPK as an oncogene, where it is overexpressed in cancer tissues compared with the nonneoplastic tissues and its expression level is related to the prognosis of different types of host malignancies. However, hnRNPK has also been identified as a tumour suppressor, as it is important for the activation of the p53/p21 pathway. Recently, the protein is also found to be exclusively related to the regulation of paraspeckles and lncRNAs such as Neat1, Lncenc1 and Xist. Interestingly, hnRNPK has been found to associate with the Kabuki-like syndrome and Au-Kline syndrome with prominent skeletal abnormalities. In vitro study revealed that the hnRNPK protein is essential for the formation of osteoclast, in line with its importance in the skeletal system.},
langid = {english},
keywords = {cancer,cell signal transduction,gene expression regulation,hnRNPK,lncRNA,skeletal remodelling}
}
@article{wangGlobalProfilingAlternative2012,
title = {Global Profiling of Alternative Splicing Events and Gene Expression Regulated by {{hnRNPH}}/{{F}}},
author = {Wang, Erming and Aslanzadeh, Vahid and Papa, Filomena and Zhu, Haiyan and family=Grange, given=Pierre, prefix=de la, useprefix=true and Cambi, Franca},
date = {2012},
journaltitle = {PloS One},
shortjournal = {PLoS ONE},
volume = {7},
number = {12},
eprint = {23284676},
eprinttype = {pmid},
pages = {e51266},
issn = {1932-6203},
doi = {10.1371/journal.pone.0051266},
abstract = {In this study, we have investigated the global impact of heterogeneous nuclear Ribonuclear Protein (hnRNP) H/F-mediated regulation of splicing events and gene expression in oligodendrocytes. We have performed a genome-wide transcriptomic analysis at the gene and exon levels in Oli-neu cells treated with siRNA that targets hnRNPH/F compared to untreated cells using Affymetrix Exon Array. Gene expression levels and regulated exons were identified with the GenoSplice EASANA algorithm. Bioinformatics analyses were performed to determine the structural properties of G tracts that correlate with the function of hnRNPH/F as enhancers vs. repressors of exon inclusion. Different types of alternatively spliced events are regulated by hnRNPH/F. Intronic G tracts density, length and proximity to the 5' splice site correlate with the hnRNPH/F enhancer function. Additionally, 6\% of genes are differently expressed upon knock down of hnRNPH/F. Genes that regulate the transition of oligodendrocyte progenitor cells to oligodendrocytes are differentially expressed in hnRNPH/F depleted Oli-neu cells, resulting in a decrease of negative regulators and an increase of differentiation-inducing regulators. The changes were confirmed in developing oligodendrocytes in vivo. This is the first genome wide analysis of splicing events and gene expression regulated by hnRNPH/F in oligodendrocytes and the first report that hnRNPH/F regulate genes that are involved in the transition from oligodendrocyte progenitor cells to oligodendrocytes.},
langid = {english},
pmcid = {PMC3524136},
keywords = {Alternative Splicing,Animals,Cell Differentiation,Exons,Gene Expression Profiling,Gene Expression Regulation,Genomics,Heterogeneous-Nuclear Ribonucleoprotein Group F-H,Mice,Oligodendroglia,Stem Cells}
}
@article{wangLateRelapsesPatients2019,
title = {Late {{Relapses}} in {{Patients With Diffuse Large B-Cell Lymphoma Treated With Immunochemotherapy}}},
author = {Wang, Yucai and Farooq, Umar and Link, Brian K. and Larson, Melissa C. and King, Rebecca L. and Maurer, Matthew J. and Allmer, Cristine and Hefazi, Mehrdad and Thompson, Carrie A. and Micallef, Ivana N. and Johnston, Patrick B. and Habermann, Thomas M. and Witzig, Thomas E. and Ansell, Stephen M. and Cerhan, James R. and Nowakowski, Grzegorz S.},
date = {2019-07-20},
journaltitle = {Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology},
shortjournal = {J Clin Oncol},
volume = {37},
number = {21},
eprint = {31170029},
eprinttype = {pmid},
pages = {1819--1827},
issn = {1527-7755},
doi = {10.1200/JCO.19.00014},
abstract = {PURPOSE: In patients with diffuse large B-cell lymphoma (DLBCL), most relapses occur within the first 2 years of diagnosis. We sought to define the rate and outcome of late relapses that occurred after achieving event-free survival at 24 months (EFS24). METHODS: We prospectively followed 1,324 patients with newly diagnosed DLBCL from 2002 to 2015 and treated with immunochemotherapy. Cumulative incidences of late DLBCL and indolent lymphoma relapses were analyzed as competing events. Postrelapse survival was defined as time from first relapse to death from any cause. RESULTS: In 847 patients who achieved EFS24, the cumulative incidence of late relapse was 6.9\% at 3 years, 9.3\% at 5 years, and 10.3\% at 8 years after EFS24. The incidence of DLBCL relapse was similar in patients with DLBCL alone at diagnosis (6.3\% at 5 years), compared with patients with concurrent indolent lymphoma at diagnosis (5.2\%; P = .46). However, the rate of indolent lymphoma relapse was higher in patients with concurrent indolent lymphoma (7.4\% v 2.1\% at 5 years; P {$<$} .01). In patients with DLBCL alone, the rate of DLBCL relapse was similar in the germinal center B-cell-like (GCB) (4.1\% at 5 years) and non-GCB (4.0\%; P = .71) subtypes, whereas the rate of indolent lymphoma relapse was higher in patients with the GCB subtype (3.9\% v 0.0\% at 5 years; P = .02). Postrelapse survival was inferior for patients who relapsed with DLBCL than for those who relapsed with indolent lymphoma (median 29.9 months v unreached; P {$<$} .01). CONCLUSION: Patients with DLBCL with a concurrent indolent lymphoma and those with the GCB subtype had a higher rate of late relapse, owing to increased relapses with indolent lymphoma. Patients who relapsed with DLBCL had a worse prognosis than those who relapsed with indolent lymphoma.},
langid = {english},
pmcid = {PMC7001527},
keywords = {Adult,Aged,Aged 80 and over,Female,Humans,Immunotherapy,Lymphoma Large B-Cell Diffuse,Male,Middle Aged,Neoplasm Recurrence Local,Progression-Free Survival,Prospective Studies}
}
@article{wangNovelPreclinicalModel2019,
title = {A Novel Preclinical Model of Cholangiocarcinoma Based on Human Aberrant {{FBXW7}} Expression.},
author = {Wang, Jingxiao and Wang, Haichuan and Peters, Michele and Ding, Ning and Ribback, Silvia and Utpatel, Kirsten and Evert, Matthias and Cigliano, Antonio and Dombrowski, Frank and Song, Xinhua and Cossu, Antonio and Xu, Meng and Che, Li and Gordan, John Dozier and Calvisi, Diego and Chen, Xin},
date = {2019-05-20},
journaltitle = {Journal of Clinical Oncology},
shortjournal = {JCO},
volume = {37},
pages = {e15624-e15624},
publisher = {Wolters Kluwer},
issn = {0732-183X},
doi = {10.1200/JCO.2019.37.15_suppl.e15624},
url = {https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.15_suppl.e15624},
urldate = {2021-09-24},
abstract = {e15624 Background: Pre-clinical models that mimic human genetic events occurring in intrahepatic cholangiocarcinoma (iCCA) are limited. The ubiquitin ligase F-box and WD repeat domain-containing 7 (FBXW7) is recognized as a tumor suppressor in many cancer types. Methods: Firstly, we determined the FBXW7 mutation frequency (n = 120) and mRNA expression (n = 87) in a collection of human iCCA. Based on the preliminary findings in human data, we generated a mouse model by hydrodynamic tail vein injection of activated/myristylated (myr-)AKT with Fbxw7ΔF, a dominant negative form of Fbxw7. Subsequently, we investigated the role of established targets of Fbxw7, namely Notch2, Yap, and c-Myc in this novel mouse model and in human CCA cell lines. Results: FBXW7 mRNA expression is almost ubiquitously downregulated (71/82; 86.6\%) in human iCCA specimens, while only 0.8\% of samples showed FBXW7 somatic mutations. In vivo, co-expression of AKT and Fbxw7ΔF triggered the development of iCCA lesions and mice were euthanized by 15 weeks post-injection due to high tumor burden. At the molecular level, a strong induction of FBXW7 canonical targets, including Yap, Notch2, and c-Myc oncoproteins, was detected. However, only c-Myc was consistently confirmed as a FBXW7 target in human CCA cell lines. Interestingly, selected ablation of c-Myc completely impaired iCCA formation in AKT/Fbxw7ΔF mice, whereas deletion of either Yap or Notch2 delayed cholangiocarcinogenesis in the same model. Furthermore, in human iCCA specimens, a strong, inverse correlation between the expression levels of FBXW7 and c-Myc was observed. Conclusions: Downregulation of FBXW7 is almost ubiquitous in human iCCA and cooperates with AKT to induce cholangiocarcinogenesis in mice. This pre-clinical mouse model could be used to test novel therapeutics targeting c-Myc, Notch2, and/or Yap.},
issue = {15\_suppl}
}
@article{wangOutSouthernEast2016,
title = {Out of Southern {{East Asia}}: The Natural History of Domestic Dogs across the World},
shorttitle = {Out of Southern {{East Asia}}},
author = {Wang, Guo-Dong and Zhai, Weiwei and Yang, He-Chuan and Wang, Lu and Zhong, Li and Liu, Yan-Hu and Fan, Ruo-Xi and Yin, Ting-Ting and Zhu, Chun-Ling and Poyarkov, Andrei D. and Irwin, David M. and Hytönen, Marjo K. and Lohi, Hannes and Wu, Chung-I. and Savolainen, Peter and Zhang, Ya-Ping},
date = {2016-01},
journaltitle = {Cell Research},
volume = {26},
number = {1},
pages = {21--33},
issn = {1748-7838},
doi = {10.1038/cr.2015.147},
url = {https://www.nature.com/articles/cr2015147},
urldate = {2018-10-25},
abstract = {The origin and evolution of the domestic dog remains a controversial question for the scientific community, with basic aspects such as the place and date of origin, and the number of times dogs were domesticated, open to dispute. Using whole genome sequences from a total of 58 canids (12 gray wolves, 27 primitive dogs from Asia and Africa, and a collection of 19 diverse breeds from across the world), we find that dogs from southern East Asia have significantly higher genetic diversity compared to other populations, and are the most basal group relating to gray wolves, indicating an ancient origin of domestic dogs in southern East Asia 33 000 years ago. Around 15 000 years ago, a subset of ancestral dogs started migrating to the Middle East, Africa and Europe, arriving in Europe at about 10 000 years ago. One of the out of Asia lineages also migrated back to the east, creating a series of admixed populations with the endemic Asian lineages in northern China before migrating to the New World. For the first time, our study unravels an extraordinary journey that the domestic dog has traveled on earth.},
langid = {english}
}
@article{wangPCBP1SuppressesTranslation2010,
title = {{{PCBP1}} Suppresses the Translation of Metastasis-Associated {{PRL-3}} Phosphatase},
author = {Wang, Haihe and Vardy, Leah A. and Tan, Cheng Peow and Loo, Jia Min and Guo, Ke and Li, Jie and Lim, Seng Gee and Zhou, Jianbiao and Chng, Wee Joo and Ng, Siok Bian and Li, Hui Xiang and Zeng, Qi},
date = {2010-07-13},
journaltitle = {Cancer Cell},
shortjournal = {Cancer Cell},
volume = {18},
number = {1},
eprint = {20609352},
eprinttype = {pmid},
pages = {52--62},
issn = {1878-3686},
doi = {10.1016/j.ccr.2010.04.028},
abstract = {Overexpression of phosphatase of regenerating liver (PRL)-3 is associated with the progression of diverse human cancers. We show that the overexpression of PRL-3 protein is not directly associated with its transcript levels, indicating the existence of an underlying posttranscriptional regulation. The 5' untranslanted region (UTR) of PRL-3 mRNA possesses triple GCCCAG motifs capable of suppressing mRNA translation through interaction with PolyC-RNA-binding protein 1 (PCBP1), which retards PRL-3 mRNA transcript incorporation into polyribosomes. Overexpression of PCBP1 inhibits PRL-3 expression and inactivates AKT, whereas knockdown of PCBP1 causes upregulation of PRL-3 protein levels, activation of AKT, and promotion of tumorigenesis. An inverse correlation between protein levels of PRL-3 and PCBP1 in human primary cancers supports the clinical relevance.},
langid = {english},
keywords = {5' Untranslated Regions,Animals,Blotting Western,Cell Line Tumor,DNA-Binding Proteins,Electrophoretic Mobility Shift Assay,Gene Expression Regulation Neoplastic,Heterogeneous-Nuclear Ribonucleoproteins,Humans,Immunoenzyme Techniques,Luciferases,Lymphatic Metastasis,Mice,Mice Nude,Neoplasm Metastasis,Neoplasm Proteins,Neoplasms,Polyribosomes,Promoter Regions Genetic,Protein Biosynthesis,Protein Tyrosine Phosphatases,Proto-Oncogene Proteins c-akt,Reverse Transcriptase Polymerase Chain Reaction,RNA Messenger,RNA Small Interfering,RNA-Binding Proteins,Spectrometry Mass Matrix-Assisted Laser Desorption-Ionization,Tissue Array Analysis,Xenograft Model Antitumor Assays}
}
@article{wangSF3B1OtherNovel2011,
title = {{{SF3B1}} and Other Novel Cancer Genes in Chronic Lymphocytic Leukemia},
author = {Wang, Lili and Lawrence, Michael S. and Wan, Youzhong and Stojanov, Petar and Sougnez, Carrie and Stevenson, Kristen and Werner, Lillian and Sivachenko, Andrey and DeLuca, David S. and Zhang, Li and Zhang, Wandi and Vartanov, Alexander R. and Fernandes, Stacey M. and Goldstein, Natalie R. and Folco, Eric G. and Cibulskis, Kristian and Tesar, Bethany and Sievers, Quinlan L. and Shefler, Erica and Gabriel, Stacey and Hacohen, Nir and Reed, Robin and Meyerson, Matthew and Golub, Todd R. and Lander, Eric S. and Neuberg, Donna and Brown, Jennifer R. and Getz, Gad and Wu, Catherine J.},
date = {2011-12-29},
journaltitle = {The New England Journal of Medicine},
shortjournal = {N. Engl. J. Med.},
volume = {365},
number = {26},
eprint = {22150006},
eprinttype = {pmid},
pages = {2497--2506},
issn = {1533-4406},
doi = {10.1056/NEJMoa1109016},
abstract = {BACKGROUND: The somatic genetic basis of chronic lymphocytic leukemia, a common and clinically heterogeneous leukemia occurring in adults, remains poorly understood. METHODS: We obtained DNA samples from leukemia cells in 91 patients with chronic lymphocytic leukemia and performed massively parallel sequencing of 88 whole exomes and whole genomes, together with sequencing of matched germline DNA, to characterize the spectrum of somatic mutations in this disease. RESULTS: Nine genes that are mutated at significant frequencies were identified, including four with established roles in chronic lymphocytic leukemia (TP53 in 15\% of patients, ATM in 9\%, MYD88 in 10\%, and NOTCH1 in 4\%) and five with unestablished roles (SF3B1, ZMYM3, MAPK1, FBXW7, and DDX3X). SF3B1, which functions at the catalytic core of the spliceosome, was the second most frequently mutated gene (with mutations occurring in 15\% of patients). SF3B1 mutations occurred primarily in tumors with deletions in chromosome 11q, which are associated with a poor prognosis in patients with chronic lymphocytic leukemia. We further discovered that tumor samples with mutations in SF3B1 had alterations in pre-messenger RNA (mRNA) splicing. CONCLUSIONS: Our study defines the landscape of somatic mutations in chronic lymphocytic leukemia and highlights pre-mRNA splicing as a critical cellular process contributing to chronic lymphocytic leukemia.},
langid = {english},
pmcid = {PMC3685413},
keywords = {Adult,Chromosome Deletion,Chromosomes Human Pair 11,DNA Neoplasm,Exome,Gene Library,High-Throughput Nucleotide Sequencing,Humans,Leukemia Lymphocytic Chronic B-Cell,Mutation,Mutation Missense,RNA Splicing,Spliceosomes}
}
@article{wangSinglecellProfilingReveals2022,
title = {Single-Cell Profiling Reveals a Memory {{B}} Cell-like Subtype of Follicular Lymphoma with Increased Transformation Risk},
author = {Wang, Xuehai and Nissen, Michael and Gracias, Deanne and Kusakabe, Manabu and Simkin, Guillermo and Jiang, Aixiang and Duns, Gerben and Sarkozy, Clementine and Hilton, Laura and Chavez, Elizabeth A. and Segat, Gabriela C. and Wong, Rachel and Kim, Jubin and Aoki, Tomohiro and Islam, Rashedul and May, Christina and Hung, Stacy and Tyshchenko, Kate and Brinkman, Ryan R. and Hirst, Martin and Karsan, Aly and Freeman, Ciara and Sehn, Laurie H. and Morin, Ryan D. and Roth, Andrew J. and Savage, Kerry J. and Craig, Jeffrey W. and Shah, Sohrab P. and Steidl, Christian and Scott, David W. and Weng, Andrew P.},
date = {2022-11-09},
journaltitle = {Nature Communications},
shortjournal = {Nat Commun},
volume = {13},
number = {1},
eprint = {36351924},
eprinttype = {pmid},
pages = {6772},
issn = {2041-1723},
doi = {10.1038/s41467-022-34408-0},
abstract = {Follicular lymphoma (FL) is an indolent cancer of mature B-cells but with ongoing risk of transformation to more aggressive histology over time. Recurrent mutations associated with transformation have been identified; however, prognostic features that can be discerned at diagnosis could be clinically useful. We present here comprehensive profiling of both tumor and immune compartments in 155 diagnostic FL biopsies at single-cell resolution by mass cytometry. This revealed a diversity of phenotypes but included two recurrent patterns, one which closely resembles germinal center B-cells (GCB) and another which appears more related to memory B-cells (MB). GCB-type tumors are enriched for EZH2, TNFRSF14, and MEF2B mutations, while MB-type tumors contain increased follicular helper T-cells. MB-type and intratumoral phenotypic diversity are independently associated with increased risk of transformation, supporting biological relevance of these features. Notably, a reduced 26-marker panel retains sufficient information to allow phenotypic profiling of future cohorts by conventional flow cytometry.},
langid = {english},
pmcid = {PMC9646774},
keywords = {B-Lymphocytes,Germinal Center,Humans,Lymphoma Follicular,Memory B Cells,Mutation}
}
@article{wangTranscriptomicCharacterizationSF3B12016,
title = {Transcriptomic {{Characterization}} of {{SF3B1 Mutation Reveals Its Pleiotropic Effects}} in {{Chronic Lymphocytic Leukemia}}},
author = {Wang, Lili and Brooks, Angela N. and Fan, Jean and Wan, Youzhong and Gambe, Rutendo and Li, Shuqiang and Hergert, Sarah and Yin, Shanye and Freeman, Samuel S. and Levin, Joshua Z. and Fan, Lin and Seiler, Michael and Buonamici, Silvia and Smith, Peter G. and Chau, Kevin F. and Cibulskis, Carrie L. and Zhang, Wandi and Rassenti, Laura Z. and Ghia, Emanuela M. and Kipps, Thomas J. and Fernandes, Stacey and Bloch, Donald B. and Kotliar, Dylan and Landau, Dan A. and Shukla, Sachet A. and Aster, Jon C. and Reed, Robin and DeLuca, David S. and Brown, Jennifer R. and Neuberg, Donna and Getz, Gad and Livak, Kenneth J. and Meyerson, Matthew M. and Kharchenko, Peter V. and Wu, Catherine J.},
date = {2016-11-14},
journaltitle = {Cancer Cell},
shortjournal = {Cancer Cell},
volume = {30},
number = {5},
eprint = {27818134},
eprinttype = {pmid},
pages = {750--763},
issn = {1535-6108, 1878-3686},
doi = {10.1016/j.ccell.2016.10.005},
url = {https://www.cell.com/cancer-cell/abstract/S1535-6108(16)30492-5},
urldate = {2019-12-21},
langid = {english},
keywords = {alternative splicing,CLL,Notch signaling,RNA sequencing,SF3B1}
}
@article{weighardtRolesHeterogeneousNuclear1996,
title = {The Roles of Heterogeneous Nuclear Ribonucleoproteins ({{hnRNP}}) in {{RNA}} Metabolism},
author = {Weighardt, Florian and Biamonti, Giuseppe and Riva, Silvano},
date = {1996},
journaltitle = {BioEssays},
volume = {18},
number = {9},
pages = {747--756},
issn = {1521-1878},
doi = {10.1002/bies.950180910},
url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/bies.950180910},
urldate = {2022-09-26},
abstract = {In eukaryotic cells, messenger RNAs are formed by extensive posttranscriptional processing of primary transcripts, assembled with a large number of proteins and processing factors in ribonucleoprotein complexes. The protein moiety of these complexes mainly constitutes a class of about 20 major polypeptides called heterogeneous nuclear ribonucleoproteins or hnRNPs. The function and the mechanism of action of hnRNPs is still not fully understood, but the identification of RNA binding domains and RNA binding specificities, and the development of new functional assays, has stimulated interest in them. In contrast to previous models that hypothesised a mere structural (histone-like) function, a more diversified and dynamic role for these proteins is now emerging. In fact, they can be viewed as a subset of the trans-acting pre-mRNA maturation factors. They might actively participate in post-transcriptional events such as regulated splicing and mRNA export. Moreover, recent data suggest an involvement of some of these proteins in molecular diseases. Here we present an overview of the most relevant properties of hnRNPs and discuss some emerging ideas on theiir roles.},
langid = {english}
}
@article{weinsteinCancerGenomeAtlas2013,
title = {The {{Cancer Genome Atlas Pan-Cancer}} Analysis Project},
author = {Weinstein, John N. and Collisson, Eric A. and Mills, Gordon B. and Shaw, Kenna R. Mills and Ozenberger, Brad A. and Ellrott, Kyle and Shmulevich, Ilya and Sander, Chris and Stuart, Joshua M.},
date = {2013-10},
journaltitle = {Nature Genetics},
shortjournal = {Nat Genet},
volume = {45},
number = {10},
pages = {1113--1120},
publisher = {Nature Publishing Group},
issn = {1546-1718},
doi = {10.1038/ng.2764},
url = {https://www.nature.com/articles/ng.2764},
urldate = {2022-05-22},
abstract = {Current clinical practice is organized according to tissue or organ of origin of tumors. Now, The Cancer Genome Atlas (TCGA) Research Network has started to identify genomic and other molecular commonalities among a dozen different types of cancer. Emerging similarities and contrasts will form the basis for targeted therapies of the future and for repurposing existing therapies by molecular rather than histological similarities of the diseases.},
issue = {10},
langid = {english},
keywords = {Cancer,Genomics}
}
@article{weirauchDeterminationInferenceEukaryotic2014,
title = {Determination and {{Inference}} of {{Eukaryotic Transcription Factor Sequence Specificity}}},
author = {Weirauch, Matthew T. and Yang, Ally and Albu, Mihai and Cote, Atina G. and Montenegro-Montero, Alejandro and Drewe, Philipp and Najafabadi, Hamed S. and Lambert, Samuel A. and Mann, Ishminder and Cook, Kate and Zheng, Hong and Goity, Alejandra and {van~Bakel}, Harm and Lozano, Jean-Claude and Galli, Mary and Lewsey, Mathew G. and Huang, Eryong and Mukherjee, Tuhin and Chen, Xiaoting and Reece-Hoyes, John S. and Govindarajan, Sridhar and Shaulsky, Gad and Walhout, Albertha J. M. and Bouget, François-Yves and Ratsch, Gunnar and Larrondo, Luis F. and Ecker, Joseph R. and Hughes, Timothy R.},
date = {2014-09-11},
journaltitle = {Cell},
shortjournal = {Cell},
volume = {158},
number = {6},
eprint = {25215497},
eprinttype = {pmid},
pages = {1431--1443},
publisher = {Elsevier},
issn = {0092-8674, 1097-4172},
doi = {10.1016/j.cell.2014.08.009},
url = {https://www.cell.com/cell/abstract/S0092-8674(14)01036-8},
urldate = {2022-02-01},
langid = {english}
}
@article{welckerFbw7TumorSuppressor2004,
title = {The {{Fbw7}} Tumor Suppressor Regulates Glycogen Synthase Kinase 3 Phosphorylation-Dependent c-{{Myc}} Protein Degradation},
author = {Welcker, Markus and Orian, Amir and Jin, Jianping and Grim, Jonathan A. and Harper, J. Wade and Eisenman, Robert N. and Clurman, Bruce E.},
date = {2004-06-15},
journaltitle = {Proceedings of the National Academy of Sciences},
shortjournal = {PNAS},
volume = {101},
number = {24},
eprint = {15150404},
eprinttype = {pmid},
pages = {9085--9090},
publisher = {National Academy of Sciences},
issn = {0027-8424, 1091-6490},
doi = {10.1073/pnas.0402770101},
url = {https://www.pnas.org/content/101/24/9085},
urldate = {2021-04-29},
abstract = {Myc proteins regulate cell growth and division and are implicated in a wide range of human cancers. We show here that Fbw7, a component of the SCFFbw7 ubiquitin ligase and a tumor suppressor, promotes proteasome-dependent c-Myc turnover in vivo and c-Myc ubiquitination in vitro. Phosphorylation of c-Myc on threonine-58 (T58) by glycogen synthase kinase 3 regulates the binding of Fbw7 to c-Myc as well as Fbw7-mediated c-Myc degradation and ubiquitination. T58 is the most frequent site of c-myc mutations in lymphoma cells, and our findings suggest that c-Myc activation is one of the key oncogenic consequences of Fbw7 loss in cancer. Because Fbw7 mediates the degradation of cyclin E, Notch, and c-Jun, as well as c-Myc, the loss of Fbw7 is likely to elicit profound effects on cell proliferation during tumorigenesis.},
langid = {english}
}
@article{wenigerMutationsTumorSuppressor2006,
title = {Mutations of the Tumor Suppressor Gene {{SOCS-1}} in Classical {{Hodgkin}} Lymphoma Are Frequent and Associated with Nuclear Phospho-{{STAT5}} Accumulation},
author = {Weniger, M. A. and Melzner, I. and Menz, C. K. and Wegener, S. and Bucur, A. J. and Dorsch, K. and Mattfeldt, T. and Barth, T. F. E. and Möller, P.},
date = {2006-04-27},
journaltitle = {Oncogene},
shortjournal = {Oncogene},
volume = {25},
number = {18},
eprint = {16532038},
eprinttype = {pmid},
pages = {2679--2684},
issn = {0950-9232},
doi = {10.1038/sj.onc.1209151},
abstract = {The suppressors of cytokine signaling (SOCS) are critically involved in the regulation of cellular proliferation, survival, and apoptosis via cytokine-induced JAK/STAT signaling. SOCS-1 silencing by aberrant DNA methylation contributes to oncogenesis in various B-cell neoplasias and carcinomas. Recently, we showed an alternative loss of SOCS-1 function due to deleterious SOCS-1 mutations in a major subset of primary mediastinal B-cell lymphoma (PMBL) and in the PMBL line MedB-1, and a biallelic SOCS-1 deletion in PMBL line Karpas1106P. For both cell lines our previous data demonstrated retarded JAK2 degradation and sustained phospho-JAK2 action leading to enhanced DNA binding of phospho-STAT5. Here, we analysed SOCS-1 in laser-microdissected Hodgkin and Reed-Sternberg (HRS) cells of classical Hodgkin lymphoma (cHL). We detected SOCS-1 mutations in HRS cells of eight of 19 cHL samples and in three of five Hodgkin lymphoma (HL)-derived cell lines by sequencing analysis. Moreover, we found a significant association between mutated SOCS-1 of isolated HRS cells and nuclear phospho-STAT5 accumulation in HRS cells of cHL tumor tissue (P {$<$} 0.01). Collectively, these findings support the concept that PMBL and cHL share many overlapping features, and that defective tumor suppressor gene SOCS-1 triggers an oncogenic pathway operative in both lymphomas.},
langid = {english},
keywords = {Amino Acid Sequence,Base Sequence,Cell Nucleus,Gene Expression Regulation Neoplastic,Genes Tumor Suppressor,Hodgkin Disease,Humans,Intracellular Signaling Peptides and Proteins,Lasers,Molecular Sequence Data,Mutation,Phosphorylation,Reed-Sternberg Cells,Repressor Proteins,Sequence Homology Amino Acid,STAT5 Transcription Factor,Suppressor of Cytokine Signaling 1 Protein,Suppressor of Cytokine Signaling Proteins}
}
@article{wesolowskiGeneExpressionProfiling2011,
title = {Gene Expression Profiling: Changing Face of Breast Cancer Classification and Management},
shorttitle = {Gene Expression Profiling},
author = {Wesolowski, Robert and Ramaswamy, Bhuvaneswari},
date = {2011},
journaltitle = {Gene Expression},
shortjournal = {Gene Expr.},
volume = {15},
number = {3},
eprint = {22268293},
eprinttype = {pmid},
pages = {105--115},
issn = {1052-2166},
doi = {10.3727/105221611x13176664479241},
abstract = {Epithelial breast malignancies are a group of several disease entities that vary in their biology and response to specific therapies. Historically, classification of different molecular types of breast cancer was done through the use of conventional methods such as tumor morphology, grade, and immunophenotyping for estrogen, progesterone, and HER-2/neu receptor expression. Such techniques, although helpful, are not sufficient to accurately predict biologic behavior of breast cancers. Over the last several years, much progress has been made in more precise identification of molecular breast cancer subtypes. Such advances hold a great promise in improving estimation of prognosis and assigning most appropriate therapies. Thanks to use of cDNA microarrays expression technology and quantitative reverse transcriptase polymerase chain reaction (RT-PCR), tumors with specific gene expression patterns can now be identified. This process is presently reshaping perceptions of how breast cancer should be classified and treated. Categorization of breast cancers by gene expression is only beginning to make its way into the daily clinical practice and likely will complement, but not replace, the conventional methods of classification.},
langid = {english},
pmcid = {PMC3772713},
keywords = {Antineoplastic Agents,Breast Neoplasms,Disease Management,Drug Resistance Neoplasm,Female,Gene Expression Profiling,Gene Expression Regulation Neoplastic,History 19th Century,History 20th Century,History 21st Century,Humans,Oligonucleotide Array Sequence Analysis,Receptor ErbB-2}
}
@article{whalleyFrameworkQualityAssessment2020,
title = {Framework for Quality Assessment of Whole Genome Cancer Sequences},
author = {Whalley, Justin P. and Buchhalter, Ivo and Rheinbay, Esther and Raine, Keiran M. and Stobbe, Miranda D. and Kleinheinz, Kortine and Werner, Johannes and Beltran, Sergi and Gut, Marta and Hübschmann, Daniel and Hutter, Barbara and Livitz, Dimitri and Perry, Marc D. and Rosenberg, Mara and Saksena, Gordon and Trotta, Jean-Rémi and Eils, Roland and Gerhard, Daniela S. and Campbell, Peter J. and Schlesner, Matthias and Gut, Ivo G.},
date = {2020-10-07},
journaltitle = {Nature Communications},
shortjournal = {Nat Commun},
volume = {11},
number = {1},
pages = {5040},
publisher = {Nature Publishing Group},
issn = {2041-1723},
doi = {10.1038/s41467-020-18688-y},
url = {https://www.nature.com/articles/s41467-020-18688-y},
urldate = {2022-05-19},
abstract = {Bringing together cancer genomes from different projects increases power and allows the investigation of pan-cancer, molecular mechanisms. However, working with whole genomes sequenced over several years in different sequencing centres requires a framework to compare the quality of these sequences. We used the Pan-Cancer Analysis of Whole Genomes cohort as a test case to construct such a framework. This cohort contains whole cancer genomes of 2832 donors from 18 sequencing centres. We developed a non-redundant set of five quality control (QC) measurements to establish a star rating system. These QC measures reflect known differences in sequencing protocol and provide a guide to downstream analyses and allow for exclusion of samples of poor quality. We have found that this is an effective framework of quality measures. The implementation of the framework is available at: https://dockstore.org/containers/quay.io/jwerner\_dkfz/pancanqc:1.2.2.},
issue = {1},
langid = {english},
keywords = {Cancer genomics,DNA sequencing,Research data}
}
@article{wienandGenomicAnalysesFlowsorted2019,
title = {Genomic Analyses of Flow-Sorted {{Hodgkin Reed-Sternberg}} Cells Reveal Complementary Mechanisms of Immune Evasion},
author = {Wienand, Kirsty and Chapuy, Bjoern and Stewart, Chip and Dunford, Andrew J. and Wu, David and Kim, Jaegil and Kamburov, Atanas and Wood, Timothy R. and Cader, Fathima Zumla and Ducar, Matthew D. and Thorner, Aaron R. and Nag, Anwesha and Heubeck, Alexander T. and Buonopane, Michael J. and Redd, Robert A. and Bojarczuk, Kamil and Lawton, Lee N. and Armand, Philippe and Rodig, Scott J. and Fromm, Jonathan R. and Getz, Gad and Shipp, Margaret A.},
date = {2019-12-10},
journaltitle = {Blood Advances},
shortjournal = {Blood Adv},
volume = {3},
number = {23},
eprint = {31816062},
eprinttype = {pmid},
pages = {4065--4080},
issn = {2473-9537},
doi = {10.1182/bloodadvances.2019001012},
abstract = {Classical Hodgkin lymphoma (cHL) is composed of rare malignant Hodgkin Reed-Sternberg (HRS) cells within an extensive, but ineffective, inflammatory/immune cell infiltrate. HRS cells exhibit near-universal somatic copy gains of chromosome 9p/9p24.1, which increase expression of the programmed cell death protein 1 (PD-1) ligands. To define genetic mechanisms of response and resistance to PD-1 blockade and identify complementary treatment targets, we performed whole-exome sequencing of flow cytometry-sorted HRS cells from 23 excisional biopsies of newly diagnosed cHLs, including 8 Epstein-Barr virus-positive (EBV+) tumors. We identified significantly mutated cancer candidate genes (CCGs) as well as somatic copy number alterations and structural variations and characterized their contribution to disease-defining immune evasion mechanisms and nuclear factor κB (NF-κB), JAK/STAT, and PI3K signaling pathways. EBV- cHLs had a higher prevalence of genetic alterations in the NF-κB and major histocompatibility complex class I antigen presentation pathways. In this young cHL cohort (median age, 26 years), we identified a predominant mutational signature of spontaneous deamination of cytosine- phosphate-guanines ("Aging"), in addition to apolipoprotein B mRNA editing catalytic polypeptide-like, activation-induced cytidine deaminase, and microsatellite instability (MSI)-associated hypermutation. In particular, the mutational burden in EBV- cHLs was among the highest reported, similar to that of carcinogen-induced tumors. Together, the overall high mutational burden, MSI-associated hypermutation, and newly identified genetic alterations represent additional potential bases for the efficacy of PD-1 blockade in cHL. Of note, recurrent cHL alterations, including B2M, TNFAIP3, STAT6, GNA13, and XPO1 mutations and 2p/2p15, 6p21.32, 6q23.3, and 9p/9p24.1 copy number alterations, were also identified in {$>$}20\% of primary mediastinal B-cell lymphomas, highlighting shared pathogenetic mechanisms in these diseases.},
langid = {english},
pmcid = {PMC6963251},
keywords = {Adult,Genomics,Humans,Immune Evasion,Reed-Sternberg Cells}
}
@article{wiestnerPointMutationsGenomic2007,
title = {Point Mutations and Genomic Deletions in {{CCND1}} Create Stable Truncated Cyclin {{D1 mRNAs}} That Are Associated with Increased Proliferation Rate and Shorter Survival},
author = {Wiestner, Adrian and Tehrani, Mahsa and Chiorazzi, Michael and Wright, George and Gibellini, Federica and Nakayama, Kazutaka and Liu, Hui and Rosenwald, Andreas and Muller-Hermelink, H. Konrad and Ott, German and Chan, Wing C. and Greiner, Timothy C. and Weisenburger, Dennis D. and Vose, Julie and Armitage, James O. and Gascoyne, Randy D. and Connors, Joseph M. and Campo, Elias and Montserrat, Emilio and Bosch, Francesc and Smeland, Erlend B. and Kvaloy, Stein and Holte, Harald and Delabie, Jan and Fisher, Richard I. and Grogan, Thomas M. and Miller, Thomas P. and Wilson, Wyndham H. and Jaffe, Elaine S. and Staudt, Louis M.},
date = {2007-06-01},
journaltitle = {Blood},
shortjournal = {Blood},
volume = {109},
number = {11},
pages = {4599--4606},
issn = {0006-4971},
doi = {10.1182/blood-2006-08-039859},
url = {https://ashpublications.org/blood/article/109/11/4599/23037/Point-mutations-and-genomic-deletions-in-CCND1},
urldate = {2019-12-21},
langid = {english}
}
@article{wildaInactivationARFMDM2p53Pathway2004,
title = {Inactivation of the {{ARF-MDM-2-p53}} Pathway in Sporadic {{Burkitt}}'s Lymphoma in Children},
author = {Wilda, M. and Bruch, J. and Harder, L. and Rawer, D. and Reiter, A. and Borkhardt, A. and Woessmann, W.},
date = {2004-03},
journaltitle = {Leukemia},
shortjournal = {Leukemia},
volume = {18},
number = {3},
eprint = {14712292},
eprinttype = {pmid},
pages = {584--588},
issn = {0887-6924},
doi = {10.1038/sj.leu.2403254},
abstract = {Burkitt's lymphomas (BLs) are characterized by an activated MYC gene that provides a constitutive proliferative signal. However, activated myc can initiate ARF-dependent activation of p53 and apoptosis as well. Data derived from cell culture and animal models suggest that the inactivation of the ARF-MDM-2-p53 apoptotic signaling pathway may be a necessary secondary event for the development of BL. This has not been tested in freshly excised BL tissue. We investigated the ARF-MDM-2-p53 pathway in tumor specimen from 24 children with sporadic BL/B-ALL. Direct sequencing revealed a point mutation in the p53 gene in four BL. Overexpression of MDM-2 was evident in 10 of the BL samples analyzed by real-time quantitative PCR. Deletion of the CDKN2A locus that encodes ARF or reduced expression of ARF could not be detected in any BL by fluorescence in situ hybridization analysis or real-time quantitative PCR, respectively. Our results indicate that the ARF-MDM-2-p53 apoptotic pathway is disrupted in about 55\% of the cases of childhood sporadic BL. We suggest that in addition to the inactivation of the ARF-MDM-2-p53 protective checkpoint function other antiapoptotic mutations may occur in a substantial part of children with sporadic BL.},
langid = {english},
keywords = {Adolescent,Burkitt Lymphoma,Case-Control Studies,Child,Child Preschool,Cyclin-Dependent Kinase Inhibitor p16,Female,Gene Deletion,Gene Expression Regulation Neoplastic,Humans,Lymphocytes,Male,Nuclear Proteins,Proto-Oncogene Proteins,Proto-Oncogene Proteins c-mdm2,RNA Neoplasm,RNA-Directed DNA Polymerase,Signal Transduction,Tumor Suppressor Protein p14ARF,Tumor Suppressor Protein p53}
}
@article{willisNewPlayersGene2019,
title = {New Players in the Gene Regulatory Network Controlling Late {{B}} Cell Differentiation},
author = {Willis, Simon N and Nutt, Stephen L},
date = {2019-06-01},
journaltitle = {Current Opinion in Immunology},
shortjournal = {Current Opinion in Immunology},
series = {Antigen Processing • {{Special}} Section on Precommited Lymphocytes},
volume = {58},
pages = {68--74},
issn = {0952-7915},
doi = {10.1016/j.coi.2019.04.007},
url = {https://www.sciencedirect.com/science/article/pii/S0952791518300827},
urldate = {2022-10-06},
abstract = {The differentiation of B cells into antibody-secreting plasma cells is associated with profound changes in morphology, lifespan, and cellular metabolism that are needed to support high rates of antibody production. These processes are driven by dramatic alterations to the transcriptional program and to the organization of the nucleus itself that in turn are regulated by the activity of a select group of transcription factors and epigenetic regulators. Although the core differentiation program is conserved in all mature B cells, subset-specific regulators, such as those found in B1 or memory B cells, provide additional complexity. Here, we review the key components of the gene regulatory network controlling B-cell terminal differentiation, with an emphasis on the new players and processes that have emerged in recent years.},
langid = {english}
}
@article{wilsonPhaseIIStudy,
title = {Phase {{II}} Study of Dose-Adjusted {{EPOCH}} and Rituximab in Untreated Diffuse Large {{B-cell}} Lymphoma with Analysis of Germinal Center and Post-Germinal Center Biomarkers},
author = {Wilson, W and Dunleavy, K and Pittaluga, S and Hegde, U and Grant, N and Steinberg, S and Raffeld, M and Gutierrez, M and Chabner, B and Staudt, L and Jaffe, E and Janik, J},
journaltitle = {J Clin Oncol},
volume = {26},
number = {16},
pages = {2717--2724}
}
@article{wilsonTargetingCellReceptor,
title = {Targeting {{B}} Cell Receptor Signaling with Ibrutinib in Diffuse Large {{B}} Cell Lymphoma.},
author = {Wilson, Wyndham H and Young, Ryan M and Schmitz, Roland and Yang, Yandan and Pittaluga, Stefania and Wright, George and Lih, Chih-Jian and Williams, P Mickey and Shaffer, Arthur L and Gerecitano, John and family=Vos, given=Sven, prefix=de, useprefix=true and Goy, Andre and Kenkre, Vaishalee P and Barr, Paul M and Blum, Kristie A and Shustov, Andrei and Advani, Ranjana and Fowler, Nathan H and Vose, Julie M and Elstrom, Rebecca L and Habermann, Thomas M and Barrientos, Jacqueline C and McGreivy, Jesse and Fardis, Maria and Chang, Betty Y and Clow, Fong and Munneke, Brian and Moussa, Davina and Beaupre, Darrin M and Staudt, Louis M},
journaltitle = {Nature Medicine},
volume = {21},
number = {8},
pages = {922--926}
}
@article{wlodarskaFOXP1GeneHighly2005,
title = {{{FOXP1}}, a Gene Highly Expressed in a Subset of Diffuse Large {{B-cell}} Lymphoma, Is Recurrently Targeted by Genomic Aberrations.},
author = {Wlodarska, I and Veyt, E and De Paepe, P and Vandenberghe, P and Nooijen, P and Theate, I and Michaux, L and Sagaert, X and Marynen, P and Hagemeijer, A and De Wolf-Peeters, C},
date = {2005-08},
journaltitle = {Leukemia},
volume = {19},
number = {8},
pages = {1299--1305}
}
@article{woosleyTGFvPromotesBreast2019,
title = {{{TGFβ}} Promotes Breast Cancer Stem Cell Self-Renewal through an {{ILEI}}/{{LIFR}} Signaling Axis},
author = {Woosley, Alec N. and Dalton, Annamarie C. and Hussey, George S. and Howley, Breege V. and Mohanty, Bidyut K. and Grelet, Simon and Dincman, Toros and Bloos, Sean and Olsen, Shaun K. and Howe, Philip H.},
date = {2019-05},
journaltitle = {Oncogene},
shortjournal = {Oncogene},
volume = {38},
number = {20},
eprint = {30692635},
eprinttype = {pmid},
pages = {3794--3811},
issn = {0950-9232},
doi = {10.1038/s41388-019-0703-z},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6525020/},
urldate = {2022-09-25},
abstract = {FAM3C/Interleukin-like EMT Inducer (ILEI) is an oncogenic member of the FAM3 cytokine family and serves essential roles in both epithelial-mesenchymal transition (EMT) and breast cancer metastasis. ILEI expression levels are regulated through a non-canonical TGFβ signaling pathway by 3’-UTR-mediated translational silencing at the mRNA level by hnRNP E1. TGFβ stimulation or silencing of hnRNP E1 increases ILEI translation and induces an EMT program that correlates to enhanced invasion and migration. Recently, EMT has been linked to the formation of breast cancer stem cells (BCSCs) that confer both tumor cell heterogeneity as well as chemoresistant properties. Herein, we demonstrate that hnRNP E1 knockdown significantly shifts normal mammary epithelial cells to mesenchymal BCSCs in vitro and in vivo. We further validate that modulating ILEI protein levels results in the abrogation of these phenotypes, promoting further investigation into the unknown mechanism of ILEI signaling that drives tumor progression. We identify LIFR as the receptor for ILEI, which mediates signaling through STAT3 to drive both EMT and BCSC formation. Reduction of either ILEI or LIFR protein levels results in reduced tumor growth, fewer tumor initiating cells and reduced metastasis within the hnRNP E1 knock-down cell populations in vivo. These results reveal a novel ligand-receptor complex that drives the formation of BCSCs and represents a unique target for the development of metastatic breast cancer therapies.},
pmcid = {PMC6525020}
}
@article{wrightGeneExpressionbasedMethod2003,
title = {A Gene Expression-Based Method to Diagnose Clinically Distinct Subgroups of Diffuse Large {{B}} Cell Lymphoma},
author = {Wright, George and Tan, Bruce and Rosenwald, Andreas and Hurt, Elaine H. and Wiestner, Adrian and Staudt, Louis M.},
date = {2003-08-19},
journaltitle = {Proceedings of the National Academy of Sciences},
shortjournal = {Proc. Natl. Acad. Sci.},
volume = {100},
number = {17},
eprint = {12900505},
eprinttype = {pmid},
pages = {9991--9996},
issn = {0027-8424, 1091-6490},
doi = {10.1073/pnas.1732008100},
url = {https://www.pnas.org/content/100/17/9991},
urldate = {2020-01-24},
abstract = {To classify cancer specimens by their gene expression profiles, we created a statistical method based on Bayes' rule that estimates the probability of membership in one of two cancer subgroups. We used this method to classify diffuse large B cell lymphoma (DLBCL) biopsy samples into two gene expression subgroups based on data obtained from spotted cDNA microarrays. The germinal center B cell-like (GCB) DLBCL subgroup expressed genes characteristic of normal germinal center B cells whereas the activated B cell-like (ABC) DLBCL subgroup expressed a subset of the genes that are characteristic of plasma cells, particularly those encoding endoplasmic reticulum and golgi proteins involved in secretion. We next used this predictor to discover these subgroups within a second set of DLBCL biopsies that had been profiled by using oligonucleotide microarrays [Shipp, M. A., et al. (2002) Nat. Med. 8, 68–74]. The GCB and ABC DLBCL subgroups identified in this data set had significantly different 5-yr survival rates after multiagent chemotherapy (62\% vs. 26\%; P ≤ 0.0051), in accord with analyses of other DLBCL cohorts. These results demonstrate the ability of this gene expression-based predictor to classify DLBCLs into biologically and clinically distinct subgroups irrespective of the method used to measure gene expression.},
langid = {english},
keywords = {Bayesian predictor,gene expression profile,microarray}
}
@article{wrightProbabilisticClassificationTool2020,
title = {A {{Probabilistic Classification Tool}} for {{Genetic Subtypes}} of {{Diffuse Large B Cell Lymphoma}} with {{Therapeutic Implications}}},
author = {Wright, George W. and Huang, Da Wei and Phelan, James D. and Coulibaly, Zana A. and Roulland, Sandrine and Young, Ryan M. and Wang, James Q. and Schmitz, Roland and Morin, Ryan D. and Tang, Jeffrey and Jiang, Aixiang and Bagaev, Aleksander and Plotnikova, Olga and Kotlov, Nikita and Johnson, Calvin A. and Wilson, Wyndham H. and Scott, David W. and Staudt, Louis M.},
date = {2020-04-13},
journaltitle = {Cancer Cell},
shortjournal = {Cancer Cell},
volume = {37},
number = {4},
eprint = {32289277},
eprinttype = {pmid},
pages = {551-568.e14},
issn = {1878-3686},
doi = {10.1016/j.ccell.2020.03.015},
abstract = {The development of precision medicine approaches for diffuse large B cell lymphoma (DLBCL) is confounded by its pronounced genetic, phenotypic, and clinical heterogeneity. Recent multiplatform genomic studies revealed the existence of genetic subtypes of DLBCL using clustering methodologies. Here, we describe an algorithm that determines the probability that a patient's lymphoma belongs to one of seven genetic subtypes based on its genetic features. This classification reveals genetic similarities between these DLBCL subtypes and various indolent and extranodal lymphoma types, suggesting a shared pathogenesis. These genetic subtypes also have distinct gene expression profiles, immune microenvironments, and outcomes following immunochemotherapy. Functional analysis of genetic subtype models highlights distinct vulnerabilities to targeted therapy, supporting the use of this classification in precision medicine trials.},
langid = {english},
keywords = {A53,BN2,DLBCL,EZB,genomic classification,LymphGen,lymphoma,MCD,N1,naive Bayes,ST2}
}
@article{wuGeneticHeterogeneityPrimary2016,
title = {Genetic Heterogeneity in Primary and Relapsed Mantle Cell Lymphomas: {{Impact}} of Recurrent {{CARD11}} Mutations},
shorttitle = {Genetic Heterogeneity in Primary and Relapsed Mantle Cell Lymphomas},
author = {Wu, Chenglin and family=Miranda, given=Noel Fcc, prefix=de, useprefix=true and Chen, Longyun and Wasik, Agata M. and Mansouri, Larry and Jurczak, Wojciech and Galazka, Krystyna and Dlugosz-Danecka, Monika and Machaczka, Maciej and Zhang, Huilai and Peng, Roujun and Morin, Ryan D. and Rosenquist, Richard and Sander, Birgitta and Pan-Hammarström, Qiang},
date = {2016-06-21},
journaltitle = {Oncotarget},
shortjournal = {Oncotarget},
volume = {7},
number = {25},
eprint = {27224912},
eprinttype = {pmid},
pages = {38180--38190},
issn = {1949-2553},
doi = {10.18632/oncotarget.9500},
abstract = {The genetic mechanisms underlying disease progression, relapse and therapy resistance in mantle cell lymphoma (MCL) remain largely unknown. Whole-exome sequencing was performed in 27 MCL samples from 13 patients, representing the largest analyzed series of consecutive biopsies obtained at diagnosis and/or relapse for this type of lymphoma. Eighteen genes were found to be recurrently mutated in these samples, including known (ATM, MEF2B and MLL2) and novel mutation targets (S1PR1 and CARD11). CARD11, a scaffold protein required for B-cell receptor (BCR)-induced NF-κB activation, was subsequently screened in an additional 173 MCL samples and mutations were observed in 5.5\% of cases. Based on in vitro cell line-based experiments, overexpression of CARD11 mutants were demonstrated to confer resistance to the BCR-inhibitor ibrutinib and NF-κB-inhibitor lenalidomide. Genetic alterations acquired in the relapse samples were found to be largely non-recurrent, in line with the branched evolutionary pattern of clonal evolution observed in most cases. In summary, this study highlights the genetic heterogeneity in MCL, in particular at relapse, and provides for the first time genetic evidence of BCR/NF-κB activation in a subset of MCL.},
langid = {english},
pmcid = {PMC5122381},
keywords = {CARD Signaling Adaptor Proteins,CARD11,Drug Resistance Neoplasm,Genetic Heterogeneity,Guanylate Cyclase,Humans,Lenalidomide,Lymphoma Mantle-Cell,mantle cell lymphoma,Mutation,NF-kappa B,NF-κB inhibitor,Pyrazoles,Pyrimidines,Recurrence,relapse,Signal Transduction,Thalidomide,Transfection,whole-exome sequencing}
}
@article{wuMolecularBasisSpecific2018,
title = {Molecular Basis for the Specific and Multivariant Recognitions of {{RNA}} Substrates by Human {{hnRNP A2}}/{{B1}}},
author = {Wu, Baixing and Su, Shichen and Patil, Deepak P. and Liu, Hehua and Gan, Jianhua and Jaffrey, Samie R. and Ma, Jinbiao},
date = {2018-01-29},
journaltitle = {Nature Communications},
shortjournal = {Nat Commun},
volume = {9},
number = {1},
pages = {420},
publisher = {Nature Publishing Group},
issn = {2041-1723},
doi = {10.1038/s41467-017-02770-z},
url = {https://www.nature.com/articles/s41467-017-02770-z},
urldate = {2022-10-04},
abstract = {Human hnRNP A2/B1 is an RNA-binding protein that plays important roles in many biological processes, including maturation, transport, and metabolism of mRNA, and gene regulation of long noncoding RNAs. hnRNP A2/B1 was reported to control the microRNAs sorting to exosomes and promote primary microRNA processing as a potential m6A “reader.” hnRNP A2/B1 contains two RNA recognition motifs that provide sequence-specific recognition of RNA substrates. Here, we determine crystal structures of tandem RRM domains of hnRNP A2/B1 in complex with various RNA substrates, elucidating specific recognitions of AGG and UAG motifs by RRM1 and RRM2 domains, respectively. Further structural and biochemical results demonstrate multivariant binding modes for sequence-diversified RNA substrates, supporting a RNA matchmaker mechanism in hnRNP A2/B1 function. Moreover, our studies in combination with bioinformatic analysis suggest that hnRNP A2/B1 may mediate effects of m6A through a “m6A switch” mechanism, instead of acting as a direct “reader” of m6A modification.},
issue = {1},
langid = {english},
keywords = {RNA modification,RNA-binding proteins,X-ray crystallography}
}
@article{wursterNusinersenSpinalMuscular2018,
title = {Nusinersen for Spinal Muscular Atrophy},
author = {Wurster, Claudia D. and Ludolph, Albert C.},
date = {2018-03-13},
journaltitle = {Therapeutic Advances in Neurological Disorders},
shortjournal = {Ther Adv Neurol Disord},
volume = {11},
eprint = {29568328},
eprinttype = {pmid},
issn = {1756-2856},
doi = {10.1177/1756285618754459},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5858681/},
urldate = {2020-09-22},
pmcid = {PMC5858681}
}
@article{xieIdentificationIndividualizedRNA2021,
title = {Identification of an Individualized {{RNA}} Binding Protein‐based Prognostic Signature for Diffuse Large {{B}}‐cell Lymphoma},
author = {Xie, Yongzhi and Luo, Ximei and He, Haiqing and Pan, Tao and He, Yizi},
date = {2021-03-21},
journaltitle = {Cancer Medicine},
shortjournal = {Cancer Med},
volume = {10},
number = {8},
eprint = {33749163},
eprinttype = {pmid},
pages = {2703--2713},
issn = {2045-7634},
doi = {10.1002/cam4.3859},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026940/},
urldate = {2022-10-04},
abstract = {RNA binding proteins (RBPs) are increasingly appreciated as being essential for normal hematopoiesis and have a critical role in the progression of hematological malignancies. However, their functional consequences and clinical significance in diffuse large B‐cell lymphoma (DLBCL) remain unknown. Here, we conducted a systematic analysis to identify RBP‐related genes affecting DLBCL prognosis based on the Gene Expression Omnibus database. By univariate and multivariate Cox proportional hazards regression (CPHR) methods, six RBPs‐related genes (CMSS1, MAEL, THOC5, PSIP1, SNIP1, and ZCCHC7) were identified closely related to the overall survival (OS) of DLBCL patients. The RBPs signature could efficiently distinguished low‐risk from high‐risk patients and could serve as an independent and reliable factor for predicting OS. Moreover, Gene Set Enrichment Analysis revealed 17 significantly enriched pathways between high‐ versus low‐risk group, including the regulation of autophagy, chronic myeloid leukemia, NOTCH signaling pathway, and B cell receptor signaling pathway. Then we developed an RBP‐based nomogram combining other clinical risk factors. The receiver operating characteristic curve analysis demonstrated high prognostic predictive efficiency of this model with the area under the curve values were 0.820 and 0.780, respectively, in the primary set and entire set. In summary, our RBP‐based model could be a novel prognostic predictor and had the potential for developing treatment targets for DLBCL., We found that six RNA binding proteins are significantly related to the overall survival of diffuse large B‐cell lymphoma (DLBCL) patients, which could potentially be served as prognostic biomarkers. Gene Set Enrichment Analysis provided insight into the underlying mechanisms in the occurrence and development of DLBCL, which laid the foundation for further basic studies.},
pmcid = {PMC8026940},
keywords = {diffuse large B-cell lymphoma,GEO,prognosis,prognostic model,RNA-binding proteins}
}
@article{xu-monetteP63ExpressionConfers2016,
title = {P63 Expression Confers Significantly Better Survival Outcomes in High-Risk Diffuse Large {{B-cell}} Lymphoma and Demonstrates P53-like and P53-Independent Tumor Suppressor Function.},
author = {Xu-Monette, Zijun Y and Zhang, Shanxiang and Li, Xin and Manyam, Ganiraju C and Wang, Xiao-Xiao and Xia, Yi and Visco, Carlo and Tzankov, Alexandar and Zhang, Li and Montes-Moreno, Santiago and Dybkaer, Karen and Chiu, April and Orazi, Attilio and Zu, Youli and Bhagat, Govind and Richards, Kristy L and Hsi, Eric D and Choi, William W L and family=Krieken, given=J Han, prefix=van, useprefix=true and Huh, Jooryung and Ponzoni, Maurilio and Ferreri, Andrés J M and Zhao, Xiaoying and Møller, Michael B and Parsons, Ben M and Winter, Jane N and Piris, Miguel A and Medeiros, L Jeffrey and Young, Ken H},
date = {2016-02},
journaltitle = {Aging},
volume = {8},
number = {2},
pages = {345--365}
}
@article{xuHnRNPAssociateHTERC2019,
title = {{{HnRNP F}}/{{H}} Associate with {{hTERC}} and Telomerase Holoenzyme to Modulate Telomerase Function and Promote Cell Proliferation},
author = {Xu, Chenzhong and Xie, Nan and Su, Yuanyuan and Sun, Zhaomeng and Liang, Yao and Zhang, Na and Liu, Doudou and Jia, Shuqin and Xing, Xiaofang and Han, Limin and Li, Guodong and Tong, Tanjun and Chen, Jun},
date = {2019-12-20},
journaltitle = {Cell Death and Differentiation},
shortjournal = {Cell Death Differ.},
eprint = {31863069},
eprinttype = {pmid},
issn = {1476-5403},
doi = {10.1038/s41418-019-0483-6},
abstract = {Human telomerase RNA component hTERC comprises multiple motifs that contribute to hTERC biogenesis, holoenzyme activity, and enzyme recruitment to telomeres. hTERC contains several guanine tracts (G-tracts) at its 5'-end, but its associated proteins and potential roles in telomerase function are still poorly understood. The heterogeneous nuclear ribonucleoproteins F, H1, and H2 (hnRNP F/H) are splicing factors that preferentially bind to poly(G)-rich sequences RNA. Here, we demonstrate that hnRNP F/H associate with both hTERC and telomerase holoenzyme to regulate telomerase activity. We reveal hnRNP F/H bind to the 5'-end region of hTERC in vitro and in vivo, and identify the first three G-tracts of hTERC and qRRM1 domain of hnRNP F/H are required for their interaction. Furthermore, hnRNP F/H also directly interact with telomerase holoenzyme. Functionally, we show that hnRNP F/H plays important roles in modulating telomerase activity and telomere length. Moreover, hnRNP F/H deletion greatly impair cancer and stem cell proliferation, and induce stem cell senescence, while hnRNP F/H overexpression delay stem cell senescence. Collectively, our findings unveil a novel role of hnRNP F/H as the binding partners of hTERC and telomerase holoenzyme to regulate telomerase function.},
langid = {english}
}
@article{xuLossIRF8Inhibits2015,
title = {Loss of {{IRF8 Inhibits}} the {{Growth}} of {{Diffuse Large B-cell Lymphoma}}},
author = {Xu, Yulian and Jiang, Lei and Fang, Jianchen and Fang, Rong and Morse, Herbert C and Ouyang, Guifang and Zhou, Jeff X},
date = {2015-08},
journaltitle = {Journal of Cancer},
volume = {6},
number = {10},
pages = {953--961}
}
@article{xuParallelComparisonIllumina2013,
title = {Parallel Comparison of {{Illumina RNA-Seq}} and {{Affymetrix}} Microarray Platforms on Transcriptomic Profiles Generated from 5-Aza-Deoxy-Cytidine Treated {{HT-29}} Colon Cancer Cells and Simulated Datasets},
author = {Xu, Xiao and Zhang, Yuanhao and Williams, Jennie and Antoniou, Eric and McCombie, W. Richard and Wu, Song and Zhu, Wei and Davidson, Nicholas O. and Denoya, Paula and Li, Ellen},
date = {2013},
journaltitle = {BMC bioinformatics},
shortjournal = {BMC Bioinformatics},
volume = {14 Suppl 9},
eprint = {23902433},
eprinttype = {pmid},
pages = {S1},
issn = {1471-2105},
doi = {10.1186/1471-2105-14-S9-S1},
abstract = {BACKGROUND: High throughput parallel sequencing, RNA-Seq, has recently emerged as an appealing alternative to microarray in identifying differentially expressed genes (DEG) between biological groups. However, there still exists considerable discrepancy on gene expression measurements and DEG results between the two platforms. The objective of this study was to compare parallel paired-end RNA-Seq and microarray data generated on 5-azadeoxy-cytidine (5-Aza) treated HT-29 colon cancer cells with an additional simulation study. METHODS: We first performed general correlation analysis comparing gene expression profiles on both platforms. An Errors-In-Variables (EIV) regression model was subsequently applied to assess proportional and fixed biases between the two technologies. Then several existing algorithms, designed for DEG identification in RNA-Seq and microarray data, were applied to compare the cross-platform overlaps with respect to DEG lists, which were further validated using qRT-PCR assays on selected genes. Functional analyses were subsequently conducted using Ingenuity Pathway Analysis (IPA). RESULTS: Pearson and Spearman correlation coefficients between the RNA-Seq and microarray data each exceeded 0.80, with 66\%\textasciitilde 68\% overlap of genes on both platforms. The EIV regression model indicated the existence of both fixed and proportional biases between the two platforms. The DESeq and baySeq algorithms (RNA-Seq) and the SAM and eBayes algorithms (microarray) achieved the highest cross-platform overlap rate in DEG results from both experimental and simulated datasets. DESeq method exhibited a better control on the false discovery rate than baySeq on the simulated dataset although it performed slightly inferior to baySeq in the sensitivity test. RNA-Seq and qRT-PCR, but not microarray data, confirmed the expected reversal of SPARC gene suppression after treating HT-29 cells with 5-Aza. Thirty-three IPA canonical pathways were identified by both microarray and RNA-Seq data, 152 pathways by RNA-Seq data only, and none by microarray data only. CONCLUSIONS: These results suggest that RNA-Seq has advantages over microarray in identification of DEGs with the most consistent results generated from DESeq and SAM methods. The EIV regression model reveals both fixed and proportional biases between RNA-Seq and microarray. This may explain in part the lower cross-platform overlap in DEG lists compared to those in detectable genes.},
langid = {english},
pmcid = {PMC3697991},
keywords = {Algorithms,Azacitidine,Colonic Neoplasms,Gene Expression Profiling,HT29 Cells,Humans,Oligonucleotide Array Sequence Analysis,Regression Analysis,RNA Neoplasm,Sensitivity and Specificity,Sequence Analysis RNA}
}
@article{yadaPhosphorylationdependentDegradationCMyc2004,
title = {Phosphorylation-Dependent Degradation of c-{{Myc}} Is Mediated by the {{F-box}} Protein {{Fbw7}}},
author = {Yada, Masayoshi and Hatakeyama, Shigetsugu and Kamura, Takumi and Nishiyama, Masaaki and Tsunematsu, Ryosuke and Imaki, Hiroyuki and Ishida, Noriko and Okumura, Fumihiko and Nakayama, Keiko and Nakayama, Keiichi I.},
date = {2004-05-19},
journaltitle = {The EMBO journal},
shortjournal = {EMBO J},
volume = {23},
number = {10},
eprint = {15103331},
eprinttype = {pmid},
pages = {2116--2125},
issn = {0261-4189},
doi = {10.1038/sj.emboj.7600217},
abstract = {The F-box protein Skp2 mediates c-Myc ubiquitylation by binding to the MB2 domain. However, the turnover of c-Myc is largely dependent on phosphorylation of threonine-58 and serine-62 in MB1, residues that are often mutated in cancer. We now show that the F-box protein Fbw7 interacts with and thereby destabilizes c-Myc in a manner dependent on phosphorylation of MB1. Whereas wild-type Fbw7 promoted c-Myc turnover in cells, an Fbw7 mutant lacking the F-box domain delayed it. Furthermore, depletion of Fbw7 by RNA interference increased both the abundance and transactivation activity of c-Myc. Accumulation of c-Myc was also apparent in mouse Fbw7-/- embryonic stem cells. These observations suggest that two F-box proteins, Fbw7 and Skp2, differentially regulate c-Myc stability by targeting MB1 and MB2, respectively.},
langid = {english},
pmcid = {PMC424394},
keywords = {Animals,Cell Cycle Proteins,Cells Cultured,Cyclin E,F-Box Proteins,F-Box-WD Repeat-Containing Protein 7,Humans,Ligases,Mice,Mice Knockout,Peptides,Phosphorylation,Proto-Oncogene Proteins c-myc,Recombinant Proteins,RNA Interference,S-Phase Kinase-Associated Proteins,Serine,Stem Cells,Threonine,Transcriptional Activation,Ubiquitin,Ubiquitin-Protein Ligases}
}
@article{yamamotoRegulationTollIL1receptormediated2004,
title = {Regulation of {{Toll}}/{{IL-1-receptor-mediated}} Gene Expression by the Inducible Nuclear Protein {{IkappaBzeta}}},
author = {Yamamoto, Masahiro and Yamazaki, Soh and Uematsu, Satoshi and Sato, Shintaro and Hemmi, Hiroaki and Hoshino, Katsuaki and Kaisho, Tsuneyasu and Kuwata, Hirotaka and Takeuchi, Osamu and Takeshige, Koichiro and Saitoh, Tatsuya and Yamaoka, Shoji and Yamamoto, Naoki and Yamamoto, Shunsuke and Muta, Tatsushi and Takeda, Kiyoshi and Akira, Shizuo},
date = {2004-07-08},
journaltitle = {Nature},
shortjournal = {Nature},
volume = {430},
number = {6996},
eprint = {15241416},
eprinttype = {pmid},
pages = {218--222},
issn = {1476-4687},
doi = {10.1038/nature02738},
abstract = {Toll-like receptors (TLRs) recognize microbial components and trigger the inflammatory and immune responses against pathogens. IkappaBzeta (also known as MAIL and INAP) is an ankyrin-repeat-containing nuclear protein that is highly homologous to the IkappaB family member Bcl-3 (refs 1-6). Transcription of IkappaBzeta is rapidly induced by stimulation with TLR ligands and interleukin-1 (IL-1). Here we show that IkappaBzeta is indispensable for the expression of a subset of genes activated in TLR/IL-1R signalling pathways. IkappaBzeta-deficient cells show severe impairment of IL-6 production in response to a variety of TLR ligands as well as IL-1, but not in response to tumour-necrosis factor-alpha. Endogenous IkappaBzeta specifically associates with the p50 subunit of NF-kappaB, and is recruited to the NF-kappaB binding site of the IL-6 promoter on stimulation. Moreover, NF-kappaB1/p50-deficient mice show responses to TLR/IL-1R ligands similar to those of IkappaBzeta-deficient mice. Endotoxin-induced expression of other genes such as Il12b and Csf2 is also abrogated in IkappaBzeta-deficient macrophages. Given that the lipopolysaccharide-induced transcription of IkappaBzeta occurs earlier than transcription of these genes, some TLR/IL-1R-mediated responses may be regulated in a gene expression process of at least two steps that requires inducible IkappaBzeta.},
langid = {english},
keywords = {Adaptor Proteins Signal Transducing,Animals,Gene Expression Regulation,Interleukin-12,Interleukin-6,Kinetics,Ligands,Lipopolysaccharides,Membrane Glycoproteins,Mice,Mice Knockout,NF-kappa B,NF-kappa B p50 Subunit,Nuclear Proteins,Promoter Regions Genetic,Receptors Cell Surface,Receptors Interleukin-1,Response Elements,Signal Transduction,Toll-Like Receptors,Tumor Necrosis Factor-alpha,Up-Regulation}
}
@article{yamamotoRoleNuclearIkB2008,
title = {Role of Nuclear {{IκB}} Proteins in the Regulation of Host Immune Responses},
author = {Yamamoto, Masahiro and Takeda, Kiyoshi},
date = {2008},
journaltitle = {Journal of Infection and Chemotherapy},
volume = {14},
number = {4},
pages = {265--269}
}
@article{yamazakiNovelIkBProtein2001,
title = {A {{Novel IκB Protein}}, {{IκB-ζ}}, {{Induced}} by {{Proinflammatory Stimuli}}, {{Negatively Regulates Nuclear Factor-κB}} in the {{Nuclei}}},
author = {Yamazaki, Soh and Muta, Tatsushi and Takeshige, Koichiro},
date = {2001-07-20},
journaltitle = {Journal of Biological Chemistry},
shortjournal = {J. Biol. Chem.},
volume = {276},
number = {29},
eprint = {11356851},
eprinttype = {pmid},
pages = {27657--27662},
issn = {0021-9258, 1083-351X},
doi = {10.1074/jbc.M103426200},
url = {http://www.jbc.org/content/276/29/27657},
urldate = {2018-09-02},
abstract = {The transcription factor nuclear factor-κB (NF-κB) plays crucial roles in a wide variety of cellular functions and its activity is strictly regulated by cytosolic inhibitors known as IκBs. We here report a new member of the IκB protein family, IκB-ζ, harboring six ankyrin repeats at its carboxyl terminus. IκB-ζ mRNA is strongly induced after stimulation by lipopolysaccharide. The induction of IκB-ζ is also observed by stimulation with interleukin-1β but not by tumor necrosis factor-α. In contrast to cytosolic IκB-α, -β, and -ε, the induced IκB-ζ localizes in the nucleus via its amino-terminal region, which shows no homology with other proteins. Transiently expressed IκB-ζ inhibits the NF-κB activity without affecting the nuclear translocation of NF-κB upon stimulation. The expressed IκB-ζ preferentially associates with the NF-κB subunit p50 rather than p65 and recombinant IκB-ζ proteins inhibit the DNA binding of the p65/p50 heterodimer and the p50/p50 homodimer. Thus, IκB-ζ negatively regulates NF-κB activity in the nucleus, possibly in order to prevent excessive inflammation. Moreover, transfection of IκB-ζ renders cells more susceptible to apoptosis induced by tumor necrosis factor-α. The proapoptotic activity of IκB-ζ further suggests that it might be one of key regulators for inflammation and other biologically relevant processes.},
langid = {english}
}
@article{yamazakiStimulusspecificInductionNovel2005,
title = {Stimulus-Specific Induction of a Novel Nuclear Factor-{{kappaB}} Regulator, {{IkappaB-zeta}}, via {{Toll}}/{{Interleukin-1}} Receptor Is Mediated by {{mRNA}} Stabilization.},
author = {Yamazaki, Soh and Muta, Tatsushi and Matsuo, Susumu and Takeshige, Koichiro},
date = {2005-01},
journaltitle = {J Biol Chem},
volume = {280},
number = {2},
pages = {1678--1687}
}
@article{yanBCRTLRSignaling2012,
title = {{{BCR}} and {{TLR}} Signaling Pathways Are Recurrently Targeted by Genetic Changes in Splenic Marginal Zone Lymphomas},
author = {Yan, Qingguo and Huang, Yuanxue and Watkins, A. James and Kocialkowski, Sylvia and Zeng, Naiyan and Hamoudi, Rifat A. and Isaacson, Peter G. and family=Leval, given=Laurence, prefix=de, useprefix=true and Wotherspoon, Andrew and Du, Ming-Qing},
date = {2012-04},
journaltitle = {Haematologica},
shortjournal = {Haematologica},
volume = {97},
number = {4},
eprint = {22102703},
eprinttype = {pmid},
pages = {595--598},
issn = {1592-8721},
doi = {10.3324/haematol.2011.054080},
abstract = {The genetics and pathogenesis of splenic marginal zone lymphoma are poorly understood. The lymphoma lacks chromosome translocation, and approximately 30\% of cases are featured by 7q deletion, but the gene targeted by the deletion is unknown. A recent study showed inactivation of A20, a "global" NF-κB negative regulator, in 1 of 12 splenic marginal zone lymphomas. To investigate further whether deregulation of the NF-κB pathway plays a role in the pathogenesis of splenic marginal zone lymphoma, we screened several NF-κB regulators for genetic changes by PCR and sequencing. Somatic mutations were found in A20 (6/46=13\%), MYD88 (6/46=13\%), CARD11 (3/34=8.8\%), but not in CD79A, CD79B and ABIN1. Interestingly, these genetic changes are largely mutually exclusive from each other and MYD88 mutation was also mutually exclusive from 7q deletion. These results strongly suggest that deregulation of the TLR (toll like receptor) and BCR (B-cell receptor) signaling pathway may play an important role in the pathogenesis of splenic marginal zone lymphoma.},
langid = {english},
pmcid = {PMC3347666},
keywords = {CARD Signaling Adaptor Proteins,Chromosome Deletion,Chromosomes Human Pair 7,DNA-Binding Proteins,Guanylate Cyclase,Humans,Intracellular Signaling Peptides and Proteins,Lymphoma B-Cell Marginal Zone,Mutation,Myeloid Differentiation Factor 88,Nuclear Proteins,Receptors Antigen B-Cell,Signal Transduction,Splenic Neoplasms,Toll-Like Receptors,Tumor Necrosis Factor alpha-Induced Protein 3,Tumor Suppressor Protein p53}
}
@article{yangDysregulationMiR212Promotes2016,
title = {Dysregulation of {{miR-212 Promotes Castration Resistance}} through {{hnRNPH1-Mediated Regulation}} of {{AR}} and {{AR-V7}}: {{Implications}} for {{Racial Disparity}} of {{Prostate Cancer}}},
shorttitle = {Dysregulation of {{miR-212 Promotes Castration Resistance}} through {{hnRNPH1-Mediated Regulation}} of {{AR}} and {{AR-V7}}},
author = {Yang, Yijun and Jia, Dingwu and Kim, Hogyoung and Abd Elmageed, Zakaria Y. and Datta, Amrita and Davis, Rodney and Srivastav, Sudesh and Moroz, Krzysztof and Crawford, Byron E. and Moparty, Krishnarao and Thomas, Raju and Hudson, Robert S. and Ambs, Stefan and Abdel-Mageed, Asim B.},
date = {2016-03-31},
journaltitle = {Clinical Cancer Research},
shortjournal = {Clinical Cancer Research},
volume = {22},
number = {7},
pages = {1744--1756},
issn = {1078-0432},
doi = {10.1158/1078-0432.CCR-15-1606},
url = {https://doi.org/10.1158/1078-0432.CCR-15-1606},
urldate = {2022-09-28},
abstract = {Purpose: The causes of disproportionate incidence and mortality of prostate cancer among African Americans (AA) remain elusive. The purpose of this study was to investigate the mechanistic role and assess clinical utility of the splicing factor heterogeneous nuclear ribonucleoprotein H1 (hnRNP H1) in prostate cancer progression among AA men.Experimental Design: We employed an unbiased functional genomics approach coupled with suppressive subtractive hybridization (SSH) and custom cDNA microarrays to identify differentially expressed genes in microdissected tumors procured from age- and tumor grade–matched AA and Caucasian American (CA) men. Validation analysis was performed in independent cohorts and tissue microarrays. The underlying mechanisms of hnRNPH1 regulation and its impact on androgen receptor (AR) expression and tumor progression were explored.Results: Aberrant coexpression of AR and hnRNPH1 and downregulation of miR-212 were detected in prostate tumors and correlate with disease progression in AA men compared with CA men. Ectopic expression of miR-212 mimics downregulated hnRNPH1 transcripts, which in turn reduced expression of AR and its splice variant AR-V7 (or AR3) in prostate cancer cells. hnRNPH1 physically interacts with AR and steroid receptor coactivator-3 (SRC-3) and primes activation of androgen-regulated genes in a ligand-dependent and independent manner. siRNA silencing of hnRNPH1 sensitized prostate cancer cells to bicalutamide and inhibited prostate tumorigenesis in vivo.Conclusions: Our findings define novel roles for hnRNPH1 as a putative oncogene, splicing factor, and an auxiliary AR coregulator. Targeted disruption of the hnRNPH1-AR axis may have therapeutic implications to improve clinical outcomes in patients with advanced prostate cancer, especially among AA men. Clin Cancer Res; 22(7); 1744–56. ©2015 AACR.}
}
@article{yangGenomicLandscapePrognostic2018,
title = {Genomic Landscape and Prognostic Analysis of Mantle Cell Lymphoma},
author = {Yang, Ping and Zhang, Weilong and Wang, Jing and Liu, Yuanyuan and An, Ran and Jing, Hongmei},
date = {2018-06},
journaltitle = {Cancer Gene Therapy},
shortjournal = {Cancer Gene Ther.},
volume = {25},
number = {5-6},
eprint = {29755111},
eprinttype = {pmid},
pages = {129--140},
issn = {1476-5500},
doi = {10.1038/s41417-018-0022-5},
abstract = {To gain insight into the molecular pathogenesis of patients with mantle cell lymphoma (MCL), next-generation whole-exome sequencing of 16 MCL patients was performed. We identified recurrent mutations in genes that are well known to be functionally relevant in MCL, including ATM (37.5\%), TP53 (31.3\%), WHSC1 (31.3\%), CCND1 (18.8\%), NOTCH2 (6.3\%), and CDKN2A (6.3\%). We also identified somatic mutations in genes for which a functional role in MCL has not been previously suspected. These genes included CCDC15, APC, CDH1, S1PR1, ATRX, BRCA2, CASP8, and NOTCH3. Further, we investigated the prognostic factors associated with MCL from clinical, pathological, and genetic mutations. Mutations of TP53 (P\,=\,0.021) was a significant prognostic factor with shorter overall survival (OS). Although there was no statistical difference, the median survival time of patients with WHSC1 mutations was shorter than those without mutations (P\,=\,0.070). Mutations in ATM and CCND1 had no prognostic value (P\,=\,0.552, 0.566). When adjusted for MCL International Prognostic Index (MIPI) or combined MCL-International Prognostic Index (MIPI-c), TP53 and WHSC1 mutations were the most important prognostic factors in MCL (P\,{$<$}\,0.05). Our data provide an unbiased view of the landscape of mutations in MCL and commend that all patients benefit from mutations of TP53 and WHSC1 at diagnosis, in addition to MIPI and MIPI-c score.},
langid = {english},
keywords = {Adult,Aged,Aged 80 and over,Disease-Free Survival,Female,Genome Human,Genome-Wide Association Study,Humans,Lymphoma Mantle-Cell,Male,Middle Aged,Mutation,Neoplasm Proteins,Survival Rate}
}
@article{yangTyrosineKinaseInhibition,
title = {Tyrosine Kinase Inhibition in Diffuse Large {{B-cell}} Lymphoma: Molecular Basis for Antitumor Activity and Drug Resistance of Dasatinib},
author = {Yang, C and Lu, P and Lee, F Y and Chadburn, A and Barrientos, J C and Leonard, J P and Ye, F and Zhang, D and Knowles, D M and Wang, Y L},
journaltitle = {Leukemia},
volume = {22},
number = {9},
pages = {1755--1766}
}
@article{yaoTCP1RingComplex2019,
title = {The {{TCP1}} Ring Complex Is Associated with Malignancy and Poor Prognosis in Hepatocellular Carcinoma.},
author = {Yao, Liheng and Zou, X. and Liu, Li},
date = {2019},
journaltitle = {International journal of clinical and experimental pathology},
volume = {12 9},
pages = {3329--3343}
}
@article{yeGenomewideMutationalSignatures2021,
title = {Genome-Wide Mutational Signatures Revealed Distinct Developmental Paths for Human {{B}} Cell Lymphomas},
author = {Ye, Xiaofei and Ren, Weicheng and Liu, Dongbing and Li, Xiaobo and Li, Wei and Wang, Xianhuo and Meng, Fei-Long and Yeap, Leng-Siew and Hou, Yong and Zhu, Shida and Casellas, Rafael and Zhang, Huilai and Wu, Kui and Pan-Hammarström, Qiang},
date = {2021-02-01},
journaltitle = {The Journal of Experimental Medicine},
shortjournal = {J Exp Med},
volume = {218},
number = {2},
eprint = {33136155},
eprinttype = {pmid},
pages = {e20200573},
issn = {1540-9538},
doi = {10.1084/jem.20200573},
abstract = {Both somatic hypermutation (SHM) and class switch recombination (CSR) are initiated by activation-induced cytidine deaminase (AID). Dysregulation of these processes has been linked to B cell lymphomagenesis. Here we performed an in-depth analysis of diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL) genomes. We characterized seven genomic mutational signatures, including two B cell tumor-specific signatures, one of which is novel and associated with aberrant SHM. We further identified two major mutational signatures (K1 and K2) of clustered mutations (kataegis) resulting from the activities of AID or error-prone DNA polymerase η, respectively. K1 was associated with the immunoglobulin (Ig) switch region mutations/translocations and the ABC subtype of DLBCL, whereas K2 was related to the Ig variable region mutations and the GCB subtype of DLBCL and FL. Similar patterns were also observed in chronic lymphocytic leukemia subtypes. Thus, alterations associated with aberrant CSR and SHM activities can be linked to distinct developmental paths for different subtypes of B cell lymphomas.},
langid = {english},
pmcid = {PMC7608067},
keywords = {B-Lymphocytes,Cell Line Tumor,Cytidine Deaminase,Female,Genome,Humans,Immunoglobulin Class Switching,Immunoglobulin Heavy Chains,Immunoglobulin Variable Region,Leukemia Lymphocytic Chronic B-Cell,Lymphoma Follicular,Lymphoma Large B-Cell Diffuse,Male,Middle Aged,Mutation,Somatic Hypermutation Immunoglobulin,Translocation Genetic}
}
@article{yehFBXW7CriticalTumor2018,
title = {{{FBXW7}}: A Critical Tumor Suppressor of Human Cancers},
shorttitle = {{{FBXW7}}},
author = {Yeh, Chien-Hung and Bellon, Marcia and Nicot, Christophe},
date = {2018-08-07},
journaltitle = {Molecular Cancer},
shortjournal = {Molecular Cancer},
volume = {17},
number = {1},
pages = {115},
issn = {1476-4598},
doi = {10.1186/s12943-018-0857-2},
url = {https://doi.org/10.1186/s12943-018-0857-2},
urldate = {2021-08-25},
abstract = {The ubiquitin-proteasome system (UPS) is involved in multiple aspects of cellular processes, such as cell cycle progression, cellular differentiation, and survival (Davis RJ et al., Cancer Cell 26:455-64, 2014; Skaar JR et al., Nat Rev Drug Discov 13:889-903, 2014; Nakayama KI and Nakayama K, Nat Rev Cancer 6:369-81, 2006). F-box and WD repeat domain containing 7 (FBXW7), also known as Sel10, hCDC4 or hAgo, is a member of the F-box protein family, which functions as the substrate recognition component of the SCF E3 ubiquitin ligase. FBXW7 is a critical tumor suppressor and one of the most commonly deregulated ubiquitin-proteasome system proteins in human cancer. FBXW7 controls proteasome-mediated degradation of oncoproteins such as cyclin E, c-Myc, Mcl-1, mTOR, Jun, Notch and AURKA. Consistent with the tumor suppressor role of FBXW7, it is located at chromosome 4q32, a genomic region deleted in more than 30\% of all human cancers (Spruck CH et al., Cancer Res 62:4535-9, 2002). Genetic profiles of human cancers based on high-throughput sequencing have revealed that FBXW7 is frequently mutated in human cancers. In addition to genetic mutations, other mechanisms involving microRNA, long non-coding RNA, and specific oncogenic signaling pathways can inactivate FBXW7 functions in cancer cells. In the following sections, we will discuss the regulation of FBXW7, its role in oncogenesis, and the clinical implications and prognostic value of loss of function of FBXW7 in human cancers.},
keywords = {C-myc,Cancer,CDC4,Cyclin E,FBXW7,HTLV,Jun,mcl-1,mTOR,Notch}
}
@article{yildizActivatingSTAT6Mutations2015,
title = {Activating {{STAT6}} Mutations in Follicular Lymphoma},
author = {Yildiz, Mehmet and Li, Hongxiu and Bernard, Denzil and Amin, Nisar A. and Ouillette, Peter and Jones, Siân and Saiya-Cork, Kamlai and Parkin, Brian and Jacobi, Kathryn and Shedden, Kerby and Wang, Shaomeng and Chang, Alfred E. and Kaminski, Mark S. and Malek, Sami N.},
date = {2015-01-22},
journaltitle = {Blood},
shortjournal = {Blood},
volume = {125},
number = {4},
eprint = {25428220},
eprinttype = {pmid},
pages = {668--679},
issn = {1528-0020},
doi = {10.1182/blood-2014-06-582650},
abstract = {Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma in the Western world. FL cell-intrinsic and cell-extrinsic factors influence FL biology and clinical outcome. To further our understanding of the genetic basis of FL, we performed whole-exome sequencing of 23 highly purified FL cases and 1 transformed FL case and expanded findings to a combined total of 114 FLs. We report recurrent mutations in the transcription factor STAT6 in 11\% of FLs and identified the STAT6 amino acid residue 419 as a novel STAT6 mutation hotspot (p.419D/G, p.419D/A, and p.419D/H). FL-associated STAT6 mutations were activating, as evidenced by increased transactivation in HEK293T cell-based transfection/luciferase reporter assays, heightened interleukin-4 (IL-4) -induced activation of target genes in stable STAT6 transfected lymphoma cell lines, and elevated baseline expression levels of STAT6 target genes in primary FL B cells harboring mutant STAT6. Mechanistically, FL-associated STAT6 mutations facilitated nuclear residency of STAT6, independent of IL-4-induced STAT6-Y641 phosphorylation. Structural modeling of STAT6 based on the structure of the STAT1-DNA complex revealed that most FL-associated STAT6 mutants locate to the STAT6-DNA interface, potentially facilitating heightened interactions. The genetic and functional data combined strengthen the recognition of the IL-4/JAK/STAT6 axis as a driver of FL pathogenesis.},
langid = {english},
pmcid = {PMC4729538},
keywords = {Active Transport Cell Nucleus,Cell Line Tumor,Cell Nucleus,Gene Expression Regulation Neoplastic,Genome-Wide Association Study,HEK293 Cells,Humans,Interleukin-4,Janus Kinases,Lymphoma Follicular,Mutation Missense,Neoplasm Proteins,Phosphorylation,STAT6 Transcription Factor,Transcriptional Activation}
}
@article{yingMEF2BMutationsLead,
title = {{{MEF2B Mutations Lead}} to {{De-Regulated Expression}} of the {{BCL6 Oncogene}} in {{Diffuse Large B-Cell Lymphoma}} and {{Follicular Lymphoma}}},
author = {Ying, Carol Y and Dominguez-Sola, David and Fabi, Melissa and Lorenz, Ivo C and Bansal, Mukesh and Califano, Andrea and Pasqualucci, Laura and Basso, Katia and Dalla-Favera, Riccardo},
journaltitle = {Blood},
volume = {120},
issue = {21 SP -}
}
@article{yinRNAbindingMotifsHnRNP2020,
title = {{{RNA-binding}} Motifs of {{hnRNP K}} Are Critical for Induction of Antibody Diversification by Activation-Induced Cytidine Deaminase},
author = {Yin, Ziwei and Kobayashi, Maki and Hu, Wenjun and Higashi, Koichi and Begum, Nasim A. and Kurokawa, Ken and Honjo, Tasuku},
date = {2020-05-26},
journaltitle = {Proceedings of the National Academy of Sciences},
volume = {117},
number = {21},
pages = {11624--11635},
publisher = {Proceedings of the National Academy of Sciences},
doi = {10.1073/pnas.1921115117},
url = {https://www.pnas.org/doi/10.1073/pnas.1921115117},
urldate = {2022-09-27}
}
@article{youngMutationsDNAbindingCodons2007,
title = {Mutations in the {{DNA-binding}} Codons of {{TP53}}, Which Are Associated with Decreased Expression of {{TRAILreceptor-2}}, Predict for Poor Survival in Diffuse Large {{B-cell}} Lymphoma},
author = {Young, K H and Weisenburger, D D and Dave, B J and Smith, L and Sanger, W and Iqbal, J and Campo, E and Delabie, J and Gascoyne, R D and Ott, G and Rimsza, L and Muller-Hermelink, H K and Jaffe, E S and Rosenwald, A and Staudt, L M and Chan, W C and Greiner, T C},
date = {2007-12},
journaltitle = {Blood},
volume = {110},
number = {13},
pages = {4396--4405}
}
@article{youngStructuralProfilesTP532008,
title = {Structural Profiles of {{TP53}} Gene Mutations Predict Clinical Outcome in Diffuse Large {{B-cell}} Lymphoma: An International Collaborative Study.},
author = {Young, Ken H and Leroy, Karen and Møller, Michael B and Colleoni, Gisele W B and Sánchez-Beato, Margarita and Kerbauy, Fábio R and Haioun, Corinne and Eickhoff, Jens C and Young, Allen H and Gaulard, Philippe and Piris, Miguel A and Oberley, Terry D and Rehrauer, William M and Kahl, Brad S and Malter, James S and Campo, Elias and Delabie, Jan and Gascoyne, Randy D and Rosenwald, Andreas and Rimsza, Lisa and Huang, James and Braziel, Rita M and Jaffe, Elaine S and Wilson, Wyndham H and Staudt, Louis M and Vose, Julie M and Chan, Wing C and Weisenburger, Dennis D and Greiner, Timothy C},
date = {2008-10},
journaltitle = {Blood},
volume = {112},
number = {8},
pages = {3088--3098}
}
@article{yugamiHnRNPUEnhancesExpression2007,
title = {{{hnRNP-U}} Enhances the Expression of Specific Genes by Stabilizing {{mRNA}}},
author = {Yugami, Masato and Kabe, Yasuaki and Yamaguchi, Yuki and Wada, Tadashi and Handa, Hiroshi},
date = {2007-01-09},
journaltitle = {FEBS Letters},
shortjournal = {FEBS Letters},
volume = {581},
number = {1},
pages = {1--7},
issn = {0014-5793},
doi = {10.1016/j.febslet.2006.11.062},
url = {https://www.sciencedirect.com/science/article/pii/S0014579306014037},
urldate = {2022-09-28},
abstract = {Heterogeneous nuclear ribonucleoproteins (hnRNPs) are thought to be involved in pre-mRNA processing. hnRNP-U, also termed scaffold attachment factor A (SAF-A), binds to pre-mRNA and nuclear matrix/scaffold attachment region DNA elements. However, its role in the regulation of gene expression is as yet poorly understood. In the present study, we show that hnRNP-U specifically enhances the expression of tumor necrosis factor α mRNA by increasing its stability, possibly through binding to the 3′ untranslated region. We also show that hnRNP-U enhances the expression of several other genes as well, including GADD45A, HEXIM1, HOXA2, IER3, NHLH2, and ZFY, by binding to and stabilizing these mRNAs. These results suggest that hnRNP-U enhances the expression of specific genes by regulating mRNA stability.},
langid = {english},
keywords = {3′ Untranslated region,Gene expression,Heterogeneous ribonucleoprotein,Tumor necrosis factor}
}
@article{zahnScalableWholegenomeSinglecell2017,
title = {Scalable Whole-Genome Single-Cell Library Preparation without Preamplification},
author = {Zahn, Hans and Steif, Adi and Laks, Emma and Eirew, Peter and VanInsberghe, Michael and Shah, Sohrab P. and Aparicio, Samuel and Hansen, Carl L.},
date = {2017-02},
journaltitle = {Nature Methods},
shortjournal = {Nat Methods},
volume = {14},
number = {2},
eprint = {28068316},
eprinttype = {pmid},
pages = {167--173},
issn = {1548-7105},
doi = {10.1038/nmeth.4140},
abstract = {Single-cell genomics is critical for understanding cellular heterogeneity in cancer, but existing library preparation methods are expensive, require sample preamplification and introduce coverage bias. Here we describe direct library preparation (DLP), a robust, scalable, and high-fidelity method that uses nanoliter-volume transposition reactions for single-cell whole-genome library preparation without preamplification. We examined 782 cells from cell lines and triple-negative breast xenograft tumors. Low-depth sequencing, compared with existing methods, revealed greater coverage uniformity and more reliable detection of copy-number alterations. Using phylogenetic analysis, we found minor xenograft subpopulations that were undetectable by bulk sequencing, as well as dynamic clonal expansion and diversification between passages. Merging single-cell genomes in silico, we generated 'bulk-equivalent' genomes with high depth and uniform coverage. Thus, low-depth sequencing of DLP libraries may provide an attractive replacement for conventional bulk sequencing methods, permitting analysis of copy number at the cell level and of other genomic variants at the population level.},
langid = {english},
keywords = {Animals,Breast Neoplasms,Cell Line Tumor,Female,Gene Library,Genomics,Humans,Lab-On-A-Chip Devices,Mice SCID,Phylogeny,Single-Cell Analysis,Xenograft Model Antitumor Assays}
}
@article{zandhuisRNABindingProteinExpression2021,
title = {{{RNA-Binding Protein Expression Alters Upon Differentiation}} of {{Human B Cells}} and {{T Cells}}},
author = {Zandhuis, Nordin D. and Nicolet, Benoit P. and Wolkers, Monika C.},
date = {2021},
journaltitle = {Frontiers in Immunology},
volume = {12},
issn = {1664-3224},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2021.717324},
urldate = {2022-09-26},
abstract = {B cells and T cells are key players in the defence against infections and malignancies. To exert their function, B cells and T cells differentiate into effector and memory cells. Tight regulation of these differentiation processes is key to prevent their malfunction, which can result in life-threatening disease. Lymphocyte differentiation relies on the appropriate timing and dosage of regulatory molecules, and post-transcriptional gene regulation (PTR) is a key player herein. PTR includes the regulation through RNA-binding proteins (RBPs), which control the fate of RNA and its translation into proteins. To date, a comprehensive overview of the RBP expression throughout lymphocyte differentiation is lacking. Using transcriptome and proteome analyses, we here catalogued the RBP expression for human B cells and T cells. We observed that even though the overall RBP expression is conserved, the relative RBP expression is distinct between B cells and T cells. Differentiation into effector and memory cells alters the RBP expression, resulting into preferential expression of different classes of RBPs. For instance, whereas naive T cells express high levels of translation-regulating RBPs, effector T cells preferentially express RBPs that modulate mRNA stability. Lastly, we found that cytotoxic CD8+ and CD4+ T cells express a common RBP repertoire. Combined, our study reveals a cell type-specific and differentiation-dependent RBP expression landscape in human lymphocytes, which will help unravel the role of RBPs in lymphocyte function.}
}
@article{zandvlietCanineLymphomaReview2016,
title = {Canine Lymphoma: A Review},
shorttitle = {Canine Lymphoma},
author = {Zandvliet, M.},
date = {2016-04-02},
journaltitle = {Veterinary Quarterly},
volume = {36},
number = {2},
eprint = {26953614},
eprinttype = {pmid},
pages = {76--104},
publisher = {Taylor \& Francis},
issn = {0165-2176},
doi = {10.1080/01652176.2016.1152633},
url = {https://doi.org/10.1080/01652176.2016.1152633},
urldate = {2021-05-13},
abstract = {Canine lymphoma (cL) is a common type of neoplasia in dogs with an estimated incidence rate of 20–100 cases per 100,000 dogs and is in many respects comparable to non-Hodgkin lymphoma in humans. Although the exact cause is unknown, environmental factors and genetic susceptibility are thought to play an important role. cL is not a single disease, and a wide variation in clinical presentations and histological subtypes is recognized. Despite this potential variation, most dogs present with generalized lymphadenopathy (multicentric form) and intermediate to high-grade lymphoma, more commonly of B-cell origin. The most common paraneoplastic sign is hypercalcemia that is associated with the T-cell immunophenotype. Chemotherapy is the treatment of choice and a doxorubicin-based multidrug protocol is currently the standard of care. A complete remission is obtained for most dogs and lasts for a median period of 7–10 months, resulting in a median survival of 10–14 months. Many prognostic factors have been reported, but stage, immunophenotype, tumor grade, and response to chemotherapy appear of particular importance. Failure to respond to chemotherapy suggests drug resistance, which can be partly attributed to the expression of drug transporters of the ABC-transporter superfamily, including P-gp and BCRP. Ultimately, most lymphomas will become drug resistant and the development of treatments aimed at reversing drug resistance or alternative treatment modalities (e.g. immunotherapy and targeted therapy) are of major importance. This review aims to summarize the relevant data on cL, as well as to provide an update of the recent literature.},
keywords = {canine,Dog,lymphoma,non-Hodgkin,review}
}
@article{zangInhibitionPanclassPI32013,
title = {Inhibition of Pan-Class {{I PI3}} Kinase by {{NVP-BKM120}} Effectively Blocks Proliferation and Induces Cell Death in Diffuse Large {{B}} Cell Lymphoma},
author = {Zang, Chuanbing and Eucker, Jan and Liu, Hongyu and Coordes, Annekatrin and Lenarz, Minoo and Possinger, Kurt and Scholz, Christian Wilfried},
date = {2013-05},
journaltitle = {Leuk lymphoma},
pages = {1--21}
}
@software{zanotelliImcSegmentationPipelinePixelclassificationBased2017,
title = {{{ImcSegmentationPipeline}}: {{A}} Pixelclassification Based Multiplexed Image Segmentation Pipeline},
shorttitle = {{{ImcSegmentationPipeline}}},
author = {Zanotelli, Vito Riccardo Tomaso and Bodenmiller, Bernd},
date = {2017-09-14},
doi = {10.5281/zenodo.3841961},
url = {https://zenodo.org/record/3841961},
urldate = {2022-02-03},
abstract = {This repository demonstrate and documents how the packages imctools, CellProfiler and Ilastik can be combined to segment highly multiplexed imaging mass cytometry images into regions corresponding to single cell slices.},
organization = {Zenodo}
}
@article{zhangCREBBPAcetyltransferaseHaploinsufficient2017,
title = {The {{CREBBP Acetyltransferase Is}} a {{Haploinsufficient Tumor Suppressor}} in {{B-cell Lymphoma}}},
author = {Zhang, Jiyuan and Vlasevska, Sofija and Wells, Victoria A. and Nataraj, Sarah and Holmes, Antony B. and Duval, Romain and Meyer, Stefanie N. and Mo, Tongwei and Basso, Katia and Brindle, Paul K. and Hussein, Shafinaz and Dalla-Favera, Riccardo and Pasqualucci, Laura},
date = {2017-03},
journaltitle = {Cancer Discovery},
shortjournal = {Cancer Discov},
volume = {7},
number = {3},
eprint = {28069569},
eprinttype = {pmid},
pages = {322--337},
issn = {2159-8290},
doi = {10.1158/2159-8290.CD-16-1417},
abstract = {Inactivating mutations of the CREBBP acetyltransferase are highly frequent in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL), the two most common germinal center (GC)-derived cancers. However, the role of CREBBP inactivation in lymphomagenesis remains unclear. Here, we show that CREBBP regulates enhancer/super-enhancer networks with central roles in GC/post-GC cell fate decisions, including genes involved in signal transduction by the B-cell receptor and CD40 receptor, transcriptional control of GC and plasma cell development, and antigen presentation. Consistently, Crebbp-deficient B cells exhibit enhanced response to mitogenic stimuli and perturbed plasma cell differentiation. Although GC-specific loss of Crebbp was insufficient to initiate malignant transformation, compound Crebbp-haploinsufficient/BCL2-transgenic mice, mimicking the genetics of FL and DLBCL, develop clonal lymphomas recapitulating the features of the human diseases. These findings establish CREBBP as a haploinsufficient tumor-suppressor gene in GC B cells and provide insights into the mechanisms by which its loss contributes to lymphomagenesis.Significance: Loss-of-function mutations of CREBBP are common and early lesions in FL and DLBCL, suggesting a prominent role in lymphoma initiation. Our studies identify the cellular program by which reduced CREBBP dosage facilitates malignant transformation, and have direct implications for targeted lymphoma therapy based on drugs affecting CREBBP-mediated chromatin acetylation. Cancer Discov; 7(3); 322-37. ©2017 AACR.This article is highlighted in the In This Issue feature, p. 235.},
langid = {english},
pmcid = {PMC5386396},
keywords = {Animals,B-Lymphocytes,Cell Differentiation,Chromatin,CREB-Binding Protein,Enhancer Elements Genetic,Epigenesis Genetic,Gene Expression Regulation Neoplastic,Genes Tumor Suppressor,Germinal Center,Haploinsufficiency,Humans,Lymphoma Follicular,Lymphoma Large B-Cell Diffuse,Mice Inbred C57BL,Mice Knockout,Plasma Cells,Proto-Oncogene Proteins c-bcl-6}
}
@article{zhangGeneticHeterogeneityDiffuse2013,
title = {Genetic Heterogeneity of Diffuse Large {{B-cell}} Lymphoma.},
author = {Zhang, Jenny and Grubor, Vladimir and Love, Cassandra L and Banerjee, Anjishnu and Richards, Kristy L and Mieczkowski, Piotr A and Dunphy, Cherie and Choi, William and Au, Wing Yan and Srivastava, Gopesh and Lugar, Patricia L and Rizzieri, David A and Lagoo, Anand S and Bernal-Mizrachi, Leon and Mann, Karen P and Flowers, Christopher and Naresh, Kikkeri and Evens, Andrew and Gordon, Leo I and Czader, Magdalena and Gill, Javed I and Hsi, Eric D and Liu, Qingquan and Fan, Alice and Walsh, Katherine and Jima, Dereje and Smith, Lisa L and Johnson, Amy J and Byrd, John C and Luftig, Micah A and Ni, Ting and Zhu, Jun and Chadburn, Amy and Levy, Shawn and Dunson, David and Dave, Sandeep S},
year = {2013},
pages = {1398--1403},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {110},
issue = {4},
pmcid = {PMC3557051},
doi = {10.1073/pnas.1205299110}
}
@article{zhangGenomicLandscapeMantle2014,
title = {The Genomic Landscape of Mantle Cell Lymphoma Is Related to the Epigenetically Determined Chromatin State of Normal {{B}} Cells},
author = {Zhang, Jenny and Jima, Dereje and Moffitt, Andrea B. and Liu, Qingquan and Czader, Magdalena and Hsi, Eric D. and Fedoriw, Yuri and Dunphy, Cherie H. and Richards, Kristy L. and Gill, Javed I. and Sun, Zhen and Love, Cassandra and Scotland, Paula and Lock, Eric and Levy, Shawn and Hsu, David S. and Dunson, David and Dave, Sandeep S.},
date = {2014-05-08},
journaltitle = {Blood},
shortjournal = {Blood},
volume = {123},
number = {19},
pages = {2988--2996},
issn = {0006-4971},
doi = {10.1182/blood-2013-07-517177},
langid = {english}
}
@article{zhangGlobalTranscriptionalNetwork2018,
title = {A Global Transcriptional Network Connecting Noncoding Mutations to Changes in Tumor Gene Expression},
author = {Zhang, Wei and Bojorquez-Gomez, Ana and Velez, Daniel Ortiz and Xu, Guorong and Sanchez, Kyle S. and Shen, John Paul and Chen, Kevin and Licon, Katherine and Melton, Collin and Olson, Katrina M. and Yu, Michael Ku and Huang, Justin K. and Carter, Hannah and Farley, Emma K. and Snyder, Michael and Fraley, Stephanie I. and Kreisberg, Jason F. and Ideker, Trey},
date = {2018-04},
journaltitle = {Nature Genetics},
shortjournal = {Nat. Genet.},
volume = {50},
number = {4},
eprint = {29610481},
eprinttype = {pmid},
pages = {613--620},
issn = {1546-1718},
doi = {10.1038/s41588-018-0091-2},
abstract = {Although cancer genomes are replete with noncoding mutations, the effects of these mutations remain poorly characterized. Here we perform an integrative analysis of 930 tumor whole genomes and matched transcriptomes, identifying a network of 193 noncoding loci in which mutations disrupt target gene expression. These 'somatic eQTLs' (expression quantitative trait loci) are frequently mutated in specific cancer tissues, and the majority can be validated in an independent cohort of 3,382 tumors. Among these, we find that the effects of noncoding mutations on DAAM1, MTG2 and HYI transcription are recapitulated in multiple cancer cell lines and that increasing DAAM1 expression leads to invasive cell migration. Collectively, the noncoding loci converge on a set of core pathways, permitting a classification of tumors into pathway-based subtypes. The somatic eQTL network is disrupted in 88\% of tumors, suggesting widespread impact of noncoding mutations in cancer.},
langid = {english},
pmcid = {PMC5893414}
}
@article{zhangHighthroughputScreenIdentifies2019,
title = {A High-Throughput Screen Identifies Small Molecule Modulators of Alternative Splicing by Targeting {{RNA G-quadruplexes}}},
author = {Zhang, Jing and Harvey, Samuel E and Cheng, Chonghui},
date = {2019-04-23},
journaltitle = {Nucleic Acids Research},
shortjournal = {Nucleic Acids Res},
volume = {47},
number = {7},
eprint = {30698802},
eprinttype = {pmid},
pages = {3667--3679},
issn = {0305-1048},
doi = {10.1093/nar/gkz036},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468248/},
urldate = {2022-10-15},
abstract = {RNA secondary structures have been increasingly recognized to play an important regulatory role in post-transcriptional gene regulation. We recently showed that RNA G-quadruplexes, which serve as cis-elements to recruit splicing factors, play a critical role in regulating alternative splicing during the epithelial-mesenchymal transition. In this study, we performed a high-throughput screen using a dual-color splicing reporter to identify chemical compounds capable of regulating G-quadruplex-dependent alternative splicing. We identify emetine and its analog cephaeline as small molecules that disrupt RNA G-quadruplexes, resulting in inhibition of G-quadruplex-dependent alternative splicing. Transcriptome analysis reveals that emetine globally regulates alternative splicing, including splicing of variable exons that contain splice site-proximal G-quadruplexes. Our data suggest the use of emetine and cephaeline for investigating mechanisms of G-quadruplex-associated alternative splicing.},
pmcid = {PMC6468248}
}
@article{zhangLenalidomideEfficacyActivated2013,
title = {Lenalidomide Efficacy in Activated {{B-cell-like}} Subtype Diffuse Large {{B-cell}} Lymphoma Is Dependent upon {{IRF4}} and Cereblon Expression.},
author = {Zhang, Ling-Hua and Kosek, Jolanta and Wang, Maria and Heise, Carla and Schafer, Peter H and Chopra, Rajesh},
date = {2013-02},
journaltitle = {Br J Haematol},
volume = {160},
number = {4},
pages = {487--502}
}
@article{zhangMatchMixeRCrossplatformNormalization2020,
title = {{{MatchMixeR}}: A Cross-Platform Normalization Method for Gene Expression Data Integration},
author = {Zhang, Serin and Shao, Jiang and Yu, Disa and Qiu, Xing and Zhang, Jinfeng},
date = {2020-01-06},
journaltitle = {Bioinformatics},
shortjournal = {Bioinformatics},
pages = {2486--2491},
issn = {1367-4803},
doi = {10.1093/bioinformatics/btz974},
abstract = {Combining gene expression (GE) profiles generated from different platforms enables previously infeasible studies due to sample size limitations. Several cross-platform normalization methods have been developed to remove the systematic differences between platforms, but they may also remove meaningful biological differences among datasets. In this work, we propose a novel approach that removes the platform, not the biological differences. Dubbed as ‘MatchMixeR’, we model platform differences by a linear mixed effects regression (LMER) model, and estimate them from matched GE profiles of the same cell line or tissue measured on different platforms. The resulting model can then be used to remove platform differences in other datasets. By using LMER, we achieve better bias-variance trade-off in parameter estimation. We also design a computationally efficient algorithm based on the moment method, which is ideal for ultra-high-dimensional LMER analysis.Compared with several prominent competing methods, MatchMixeR achieved the highest after-normalization concordance. Subsequent differential expression analyses based on datasets integrated from different platforms showed that using MatchMixeR achieved the best trade-off between true and false discoveries, and this advantage is more apparent in datasets with limited samples or unbalanced group proportions.Our method is implemented in a R-package, ‘MatchMixeR’, freely available at: https://github.com/dy16b/Cross-Platform-Normalization.Supplementary data are available at Bioinformatics online.},
issue = {btz974}
}
@article{zhangModelbasedAnalysisChIPSeq2008,
title = {Model-Based Analysis of {{ChIP-Seq}} ({{MACS}})},
author = {Zhang, Yong and Liu, Tao and Meyer, Clifford A. and Eeckhoute, Jérôme and Johnson, David S. and Bernstein, Bradley E. and Nusbaum, Chad and Myers, Richard M. and Brown, Myles and Li, Wei and Liu, X. Shirley},
date = {2008},
journaltitle = {Genome Biology},
shortjournal = {Genome Biol},
volume = {9},
number = {9},
eprint = {18798982},
eprinttype = {pmid},
pages = {R137},
issn = {1474-760X},
doi = {10.1186/gb-2008-9-9-r137},
abstract = {We present Model-based Analysis of ChIP-Seq data, MACS, which analyzes data generated by short read sequencers such as Solexa's Genome Analyzer. MACS empirically models the shift size of ChIP-Seq tags, and uses it to improve the spatial resolution of predicted binding sites. MACS also uses a dynamic Poisson distribution to effectively capture local biases in the genome, allowing for more robust predictions. MACS compares favorably to existing ChIP-Seq peak-finding algorithms, and is freely available.},
langid = {english},
pmcid = {PMC2592715},
keywords = {Algorithms,Cell Line Tumor,Chromatin Immunoprecipitation,Hepatocyte Nuclear Factor 3-alpha,Humans,Models Genetic,Oligonucleotide Array Sequence Analysis}
}
@article{zhangPCBP1ImportantMediator2014,
title = {{{PCBP1}} Is an Important Mediator of {{TGF-β-induced}} Epithelial to Mesenchymal Transition in Gall Bladder Cancer Cell Line {{GBC-SD}}},
author = {Zhang, Hang-Yu and Dou, Ke-Feng},
date = {2014-08-01},
journaltitle = {Molecular Biology Reports},
shortjournal = {Mol Biol Rep},
volume = {41},
number = {8},
pages = {5519--5524},
issn = {1573-4978},
doi = {10.1007/s11033-014-3428-7},
url = {https://doi.org/10.1007/s11033-014-3428-7},
urldate = {2022-09-28},
abstract = {Gall bladder carcinoma (GBC) is the seventh most common cancer across the globe and the most common malignancy of the biliary tract. Most GBC related deaths occur due to secondary progression and metastasis to distant organs. Epithelial–mesenchymal transition (EMT) is an important pre-requisite for tumor metastasis, however its mechanism in GBC has not yet been defined. Using the GBC-SD cell line, we have uncovered an important mediator, poly r(C) binding protein-1 (PCBP1), of transforming growth factor-beta (TGF-β)-induced EMT in GBC. Our results show that TGF-β treatment resulted in PCBP1 phosphorylation in accordance with similar observation in other model systems. We further showed through gain- and loss-of-function assays that PCBP1 expression levels regulate the capacity of GBC-SD cells to migrate and invade in vitro. Finally, our results showed that PCBP1 expression levels also regulate generation of CD44+CD24− progenitor cell population in GBC-SD cells after TGF-β treatment. Cumulatively, our results indicate, pending further validation, that PCBP1 might be a prognostic marker for GBC metastasis.},
langid = {english}
}
@article{zhangPCBP1RegulatesAlternative2010,
title = {{{PCBP-1}} Regulates Alternative Splicing of the {{CD44}} Gene and Inhibits Invasion in Human Hepatoma Cell Line {{HepG2}} Cells},
author = {Zhang, Tong and Huang, Xian-Hong and Dong, Lan and Hu, Deqing and Ge, Changhui and Zhan, Yi-Qun and Xu, Wang-Xiang and Yu, Miao and Li, Wei and Wang, Xiaohui and Tang, Liujun and Li, Chang-Yan and Yang, Xiao-Ming},
date = {2010-04-02},
journaltitle = {Molecular Cancer},
shortjournal = {Molecular Cancer},
volume = {9},
number = {1},
pages = {72},
issn = {1476-4598},
doi = {10.1186/1476-4598-9-72},
url = {https://doi.org/10.1186/1476-4598-9-72},
urldate = {2022-09-28},
abstract = {PCBP1 (or alpha CP1 or hnRNP E1), a member of the PCBP family, is widely expressed in many human tissues and involved in regulation of transcription, transportation process, and function of RNA molecules. However, the role of PCBP1 in CD44 variants splicing still remains elusive.},
keywords = {CD44 Variant,Hepatocyte Growth Factor,HepG2 Cell,hnRNP Protein,Human Hepatoma Cell Line HepG2}
}
@article{zhangPolyBindingProtein2020,
title = {Poly {{C Binding Protein}} 1 {{Regulates}} P62/{{SQSTM1 mRNA Stability}} and {{Autophagic Degradation}} to {{Repress Tumor Progression}}},
author = {Zhang, Wenliang and Zhang, Shaoyang and Guan, Wen and Huang, Zhicong and Kong, Jianqiu and Huang, Chunlong and Wang, Haihe and Yang, Shulan},
date = {2020},
journaltitle = {Frontiers in Genetics},
volume = {11},
issn = {1664-8021},
url = {https://www.frontiersin.org/articles/10.3389/fgene.2020.00930},
urldate = {2022-09-28},
abstract = {Accumulating evidence show that Poly C Binding Protein 1 (PCBP1) is deleted in distinct types of tumors as a novel tumor suppressor, but its tumor suppression mechanism remains elusive. Here, we firstly describe that downregulation of PCBP1 is significantly associated with clinical ovarian tumor progression. Mechanistically, PCBP1 overexpression affects various autophagy-related genes expression at various expression levels to attenuate the intrinsic cell autophagy, including the autophagy-initiating ULK, ATG12, ATG7 as well as the bona fide marker of autophagosome, LC3B. Accordingly, knockdown of the endogenous PCBP1 in turn enhances autophagy and less cell death. Meanwhile, PCBP1 upregulates p62/SQSTM1 via inhibition p62/SQSTM1 autophagolysome and proteasome degradation as well as its mRNA stability, consequently accompanying with the caspase 3 or 8 activation for tumor cell apoptosis. Importantly, clinical ovary cancer sample analysis consistently validates the relevance of PCBP1 expression to both p62/SQSTM1 and caspase-8 to overall survival, and indicates PCBP1 may be a master player to repress tumor initiation. Taken together, our results uncover the tumorigenic mechanism of PCBP1 depletion and suggest that inhibition of tumor cell autophagy with autophagic inhibitors could be an effective therapeutical strategy for PCBP1-deficient tumor.}
}
@article{zhangRegulationGerminalCenter2016,
title = {Regulation of Germinal Center {{B-cell}} Differentiation},
author = {Zhang, Yang and Garcia-Ibanez, Laura and Toellner, Kai-Michael},
date = {2016},
journaltitle = {Immunological Reviews},
volume = {270},
number = {1},
pages = {8--19},
issn = {1600-065X},
doi = {10.1111/imr.12396},
url = {https://onlinelibrary.wiley.com/doi/abs/10.1111/imr.12396},
urldate = {2022-10-06},
abstract = {Germinal centers (GC) are the main sites where antigen-activated B-cell clones expand and undergo immunoglobulin gene hypermutation and selection. Iterations of this process will lead to affinity maturation, replicating Darwinian evolution on the cellular level. GC B-cell selection can lead to four different outcomes: further expansion and evolution, apoptosis (non-selection), or output from the GC with differentiation into memory B cells or plasma cells. T-helper cells in GC have been shown to have a central role in regulating B-cell selection by sensing the density of major histocompatibility complex (MHC):peptide antigen complexes. Antigen is provided on follicular dendritic cells in the form of immune complex. Antibody on these immune complexes regulates antigen accessibility by shielding antigen from B-cell receptor access. Replacement of antibody on immune complexes by antibody generated from GC-derived plasma cell output will gradually reduce the availability of antigen. This antibody feedback can lead to a situation where a slow rise in selection stringency caused by a changing environment leads to directional evolution toward higher affinity antibody.},
langid = {english},
keywords = {affinity maturation,B-cell selection,cytokines,germinal center,immune complex,Tfh cells}
}
@article{zhaoCrossMapVersatileTool2014,
title = {{{CrossMap}}: A Versatile Tool for Coordinate Conversion between Genome Assemblies},
shorttitle = {{{CrossMap}}},
author = {Zhao, Hao and Sun, Zhifu and Wang, Jing and Huang, Haojie and Kocher, Jean-Pierre and Wang, Liguo},
date = {2014-04-01},
journaltitle = {Bioinformatics},
shortjournal = {Bioinformatics},
volume = {30},
number = {7},
pages = {1006--1007},
issn = {1367-4803},
doi = {10.1093/bioinformatics/btt730},
url = {https://academic.oup.com/bioinformatics/article/30/7/1006/234947},
urldate = {2020-01-24},
abstract = {Abstract. Motivation: Reference genome assemblies are subject to change and refinement from time to time. Generally, researchers need to convert the results th},
langid = {english}
}
@article{zhengHaplotypingGermlineCancer2016,
title = {Haplotyping Germline and Cancer Genomes with High-Throughput Linked-Read Sequencing},
author = {Zheng, Grace X Y and Lau, Billy T and Schnall-Levin, Michael and Jarosz, Mirna and Bell, John M and Hindson, Christopher M and Kyriazopoulou-Panagiotopoulou, Sofia and Masquelier, Donald A and Merrill, Landon and Terry, Jessica M and Mudivarti, Patrice A and Wyatt, Paul W and Bharadwaj, Rajiv and Makarewicz, Anthony J and Li, Yuan and Belgrader, Phillip and Price, Andrew D and Lowe, Adam J and Marks, Patrick and Vurens, Gerard M and Hardenbol, Paul and Montesclaros, Luz and Luo, Melissa and Greenfield, Lawrence and Wong, Alexander and Birch, David E and Short, Steven W and Bjornson, Keith P and Patel, Pranav and Hopmans, Erik S and Wood, Christina and Kaur, Sukhvinder and Lockwood, Glenn K and Stafford, David and Delaney, Joshua P and Wu, Indira and Ordonez, Heather S and Grimes, Susan M and Greer, Stephanie and Lee, Josephine Y and Belhocine, Kamila and Giorda, Kristina M and Heaton, William H and McDermott, Geoffrey P and Bent, Zachary W and Meschi, Francesca and Kondov, Nikola O and Wilson, Ryan and Bernate, Jorge A and Gauby, Shawn and Kindwall, Alex and Bermejo, Clara and Fehr, Adrian N and Chan, Adrian and Saxonov, Serge and Ness, Kevin D and Hindson, Benjamin J and Ji, Hanlee P},
date = {2016},
journaltitle = {Nature Biotechnology},
volume = {34},
number = {3},
eprint = {26829319},
eprinttype = {pmid},
pages = {303--311},
issn = {1087-0156},
doi = {10.1038/nbt.3432},
url = {http://dx.doi.org/10.1038/nbt.3432},
abstract = {Haplotyping of human chromosomes is a prerequisite for cataloguing the full repertoire of genetic variation. We present a microfluidics-based, linked-read sequencing technology that can phase and haplotype germline and cancer genomes using nanograms of input DNA. This high-throughput platform prepares barcoded libraries for short-read sequencing and computationally reconstructs long-range haplotype and structural variant information. We generate haplotype blocks in a nuclear trio that are concordant with expected inheritance patterns and phase a set of structural variants. We also resolve the structure of the EML4-ALK gene fusion in the NCI-H2228 cancer cell line using phased exome sequencing. Finally, we assign genetic aberrations to specific megabase-scale haplotypes generated from whole-genome sequencing of a primary colorectal adenocarcinoma. This approach resolves haplotype information using up to 100 times less genomic DNA than some methods and enables the accurate detection of structural variants.}
}
@article{zhengMassivelyParallelDigital2017,
title = {Massively Parallel Digital Transcriptional Profiling of Single Cells},
author = {Zheng, Grace X. Y. and Terry, Jessica M. and Belgrader, Phillip and Ryvkin, Paul and Bent, Zachary W. and Wilson, Ryan and Ziraldo, Solongo B. and Wheeler, Tobias D. and McDermott, Geoff P. and Zhu, Junjie and Gregory, Mark T. and Shuga, Joe and Montesclaros, Luz and Underwood, Jason G. and Masquelier, Donald A. and Nishimura, Stefanie Y. and Schnall-Levin, Michael and Wyatt, Paul W. and Hindson, Christopher M. and Bharadwaj, Rajiv and Wong, Alexander and Ness, Kevin D. and Beppu, Lan W. and Deeg, H. Joachim and McFarland, Christopher and Loeb, Keith R. and Valente, William J. and Ericson, Nolan G. and Stevens, Emily A. and Radich, Jerald P. and Mikkelsen, Tarjei S. and Hindson, Benjamin J. and Bielas, Jason H.},
date = {2017-01-16},
journaltitle = {Nature Communications},
shortjournal = {Nat Commun},
volume = {8},
eprint = {28091601},
eprinttype = {pmid},
pages = {14049},
issn = {2041-1723},
doi = {10.1038/ncomms14049},
abstract = {Characterizing the transcriptome of individual cells is fundamental to understanding complex biological systems. We describe a droplet-based system that enables 3' mRNA counting of tens of thousands of single cells per sample. Cell encapsulation, of up to 8 samples at a time, takes place in ∼6\,min, with ∼50\% cell capture efficiency. To demonstrate the system's technical performance, we collected transcriptome data from ∼250k single cells across 29 samples. We validated the sensitivity of the system and its ability to detect rare populations using cell lines and synthetic RNAs. We profiled 68k peripheral blood mononuclear cells to demonstrate the system's ability to characterize large immune populations. Finally, we used sequence variation in the transcriptome data to determine host and donor chimerism at single-cell resolution from bone marrow mononuclear cells isolated from transplant patients.},
langid = {english},
pmcid = {PMC5241818},
keywords = {Cell Line,Female,Humans,Leukocytes Mononuclear,Male,RNA Messenger,Single-Cell Analysis,Transcriptome}
}
@article{zhouSporadicEndemicBurkitt2019,
title = {Sporadic and Endemic {{Burkitt}} Lymphoma Have Frequent {{FOXO1}} Mutations but Distinct Hotspots in the {{AKT}} Recognition Motif},
author = {Zhou, Peixun and Blain, Alex E. and Newman, Alexander M. and Zaka, Masood and Chagaluka, George and Adlar, Filbert R. and Offor, Ugonna T. and Broadbent, Casey and Chaytor, Lewis and Whitehead, Amber and Hall, Amy and O'Connor, Hettie and Van Noorden, Susan and Lampert, Irvin and Bailey, Simon and Molyneux, Elizabeth and Bacon, Chris M. and Bomken, Simon and Rand, Vikki},
date = {2019-07-23},
journaltitle = {Blood Advances},
shortjournal = {Blood Adv},
volume = {3},
number = {14},
eprint = {31300419},
eprinttype = {pmid},
pages = {2118--2127},
issn = {2473-9537},
doi = {10.1182/bloodadvances.2018029546},
abstract = {FOXO1 has an oncogenic role in adult germinal center-derived lymphomas, in which mutations, predominately within the AKT recognition motif, cause nuclear retention of FOXO1, resulting in increased cell proliferation. To determine the prevalence and distribution of FOXO1 mutations in pediatric Burkitt lymphoma (BL), we sequenced a large number of sporadic and endemic BL patient samples. We report a high frequency of FOXO1 mutations in both sporadic and endemic BL at diagnosis, occurring in 23/78 (29\%) and 48/89 (54\%) samples, respectively, as well as 8/16 (50\%) cases at relapse. Mutations of T24 were the most common in sporadic BL but were rare in endemic cases, in which mutations of residue S22, also within the AKT recognition motif, were the most frequent. FOXO1 mutations were almost always present in the major tumor cell clone but were not associated with outcome. Analysis of other recurrent mutations reported in BL revealed that FOXO1 mutations were associated with mutations of DDX3X and ARID1A, but not MYC, TCF3/ID3, or members of the phosphatidylinositol 3-kinase signaling pathway. We further show common nuclear retention of the FOXO1 protein, irrespective of mutation status, suggesting alternative unknown mechanisms for maintaining FOXO1 transcriptional activity in BL. CRISPR/Cas9 knockout of FOXO1 in an endemic cell line produced a significant decrease in cell proliferation, supporting an oncogenic role for FOXO1 in endemic BL. Thus, FOXO1 is frequently mutated in both sporadic and endemic BL and may offer a potential therapeutic target for pediatric BL patients worldwide.},
langid = {english},
pmcid = {PMC6650741},
keywords = {Adolescent,Binding Sites,Burkitt Lymphoma,Child,Child Preschool,DEAD-box RNA Helicases,DNA-Binding Proteins,Female,Forkhead Box Protein O1,Gene Frequency,Gene Knockout Techniques,High-Throughput Nucleotide Sequencing,Humans,Infant,Infant Newborn,Kaplan-Meier Estimate,Male,Mutation,Neoplasm Staging,Nucleotide Motifs,Protein Binding,Proto-Oncogene Proteins c-akt,Transcription Factors,Young Adult}
}
@article{zhouStrongExpressionEZH2,
title = {Strong Expression of {{EZH2}} and Accumulation of Trimethylated {{H3K27}} in Diffuse Large {{B-cell}} Lymphoma Independent of Cell of Origin and {{EZH2}} Codon 641 Mutation.},
author = {Zhou, Zheng and Gao, Juehua and Popovic, Relja and Wolniak, Kristy and Parimi, Vamsi and Winter, Jane N and Licht, Jonathan D and Chen, Yi-Hua},
journaltitle = {Leuk lymphoma},
volume = {56},
number = {10},
pages = {2895--2901}
}
@article{ziakasFcgRIIaH131RVariantAssociated2016,
title = {{{FcγRIIa-H131R}} Variant Is Associated with Inferior Response in Diffuse Large {{B}} Cell Lymphoma: {{A}} Meta-Analysis of Genetic Risk.},
author = {Ziakas, Panayiotis D and Poulou, Loukia S and Zintzaras, Elias},
date = {2016-11},
journaltitle = {Journal of B.U.ON. : official journal of the Balkan Union of Oncology},
volume = {21},
number = {6},
pages = {1454--1458}
}