add some PMCIDs

pages = {e310-e312},

issn = {1592-8721},

doi = {10.3324/haematol.2016.161711},

issue = {8},

langid = {english}

}

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}

}

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}

}

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}

}

pages = {58638--58648},

issn = {1949-2553},

doi = {10.18632/oncotarget.10716},

abstract = {Oncotarget | https://doi.org/10.18632/oncotarget.10716 Makhdum Ahmed, Leo Zhang, Krystle Nomie, Laura Lam, Michael Wang}

}

pages = {68},

issn = {1474-760X},

doi = {10.1186/s13059-021-02283-5},

abstract = {The ability of nanopore sequencing to simultaneously detect modified nucleotides while producing long reads makes it ideal for detecting and phasing allele-specific methylation. However, there is currently no complete software for detecting SNPs, phasing haplotypes, and mapping methylation to these from nanopore sequence data. Here, we present NanoMethPhase, a software tool to phase 5-methylcytosine from nanopore sequencing. We also present SNVoter, which can post-process nanopore SNV calls to improve accuracy in low coverage regions. Together, these tools can accurately detect allele-specific methylation genome-wide using nanopore sequence data with low coverage of about ten-fold redundancy.},

keywords = {Allele-specific methylation,NanoMethPhase,Nanopore sequencing,Phasing}

}

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}

}

publisher = {Elsevier},

issn = {0092-8674, 1097-4172},

doi = {10.1016/j.cell.2015.08.011},

langid = {english}

}

pages = {2493--2507},

issn = {0006-4971},

doi = {10.1182/blood.2022018248},

abstract = {Molecular heterogeneity of diffuse large B-cell lymphoma (DLBCL) underlies the variable outcomes achieved with immunochemotherapy. However, outcomes of gene expression profiling (GEP)–defined molecular subgroups in a real-world DLBCL population remain unknown. Here we examined the prevalence and outcomes of molecular subgroups in an unselected population of 1149 patients with de novo DLBCL in British Columbia, Canada. Evaluable biopsies were profiled by fluorescence in situ hybridization (FISH), immunohistochemistry, and digital GEP to assign cell-of-origin and the so-called “double-hit signature” (DHITsig)—a signature originally described as being characteristic for high-grade B-cell lymphoma with MYC and BCL2 rearrangements (HGBCL-DH-BCL2). DHITsig was expressed in 21\% of 431 germinal center B-cell-like (GCB)–DLBCL and all 55 Burkitt lymphomas examined. Reflecting this latter finding, DHITsig has been renamed the “dark zone signature” (DZsig). DZsigpos-DLBCL, non-DZsigpos GCB-DLBCL and activated B-cell-like (ABC)–DLBCL were associated with a 2 year overall survival of 57\%, 89\%, and 71\%, respectively. 62\% of DZsigpos tumors were negative for HGBCL-DH-BCL2 by FISH, but were associated with outcomes similar to HGBCL-DH-BCL2. A small group of HGBCL-DH-BCL2 that lacked DZsig expression had different molecular features compared with DZsig-expressing HGBCL-DH-BCL2 and were associated with favorable outcomes comparable to DLBCL, not otherwise specified. DZsigpos and ABC-DLBCL had a shorter diagnosis-to-treatment interval (DTI) than GCB-DLBCL, with this metric being associated with outcome. In conclusion, DZsig expression extends beyond HGBCL-DH-BCL2 and captures a poor-prognosis DLBCL subgroup with short DTI, including patients unidentifiable by routine FISH testing, that should be considered for treatment intensification or novel therapies in prospective trials.}

}

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}

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}

}

pages = {697923},

issn = {2314-6133},

doi = {10.1155/2014/697923},

abstract = {Aptamers are short nucleic acid oligos. They may serve as both drugs and drug-carriers. Their use as diagnostic tools is also evident. They can be generated using various experimental, theoretical, and computational techniques. The systematic evolution of ligands by exponential enrichment which uses iterative screening of nucleic acid libraries is a popular experimental technique. Theory inspired methodology entropy-based seed-and-grow strategy that designs aptamer templates to bind specifically to targets is another one. Aptamers are predicted to be highly useful in producing general drugs and theranostic drugs occasionally for certain diseases like cancer, Alzheimer's disease, and so on. They bind to various targets like lipids, nucleic acids, proteins, small organic compounds, and even entire organisms. Aptamers may also serve as drug-carriers or nanoparticles helping drugs to get released in specific target regions. Due to better target specific physical binding properties aptamers cause less off-target toxicity effects. Therefore, search for aptamer based drugs, drug-carriers, and even diagnostic tools is expanding fast. The biophysical properties in relation to the target specific binding phenomena of aptamers, energetics behind the aptamer transport of drugs, and the consequent biological implications will be discussed. This review will open up avenues leading to novel drug discovery and drug delivery.},

pmcid = {PMC4177733}

}

eprinttype = {pmid},

pages = {759--763},

issn = {0002-9440},

pmcid = {PMC1867166}

}

pages = {11.10.1-11.10.33},

issn = {1934-340X},

doi = {10.1002/0471250953.bi1110s43},

abstract = {This unit describes how to use BWA and the Genome Analysis Toolkit (GATK) to map genome sequencing data to a reference and produce high-quality variant calls that can be used in downstream analyses. The complete workflow includes the core NGS data-processing steps that are necessary to make the raw data suitable for analysis by the GATK, as well as the key methods involved in variant discovery using the GATK. Curr. Protoc. Bioinform. 43:11.10.1-11.10.33. © 2013 by John Wiley \& Sons, Inc.},

langid = {english},

keywords = {exome,genotyping,NGS,variant detection,WGS}

pages = {41--51},

issn = {0303-2647},

doi = {10.1016/j.biosystems.2018.12.009},

abstract = {Gene expression microarray classification is a crucial research field as it has been employed in cancer prediction and diagnosis systems. Gene expression data are composed of dozens of samples characterized by thousands of genes. Hence, an accurate and effective classification of such samples is a challenge. Machine learning techniques have been broadly utilized to build substantial and precise classification models. This paper proposes a new classification technique for gene expression data, which is called Modified k-nearest neighbor (MKNN). MKNN is applied in two scenarios namely; smallest modified KNN (SMKNN) and largest modified KNN (LMKNN). Both implementations are undertaken to enhance the performance of KNN. The key idea is to employ robust neighbors from training data by using a new weighting strategy. Several experiments have been performed on six different gene expression datasets. Experiments have shown that MKNN in its both scenarios outperforms traditional as well as recent ones. MKNN has been compared against (i) KNN, (ii) weighted KNN, (iii) support vector machine (SVM), (iv) fuzzy support vector machine, (v) brain emotional learning (BEL) in terms of classification accuracy, precision, and recall. On the other hand, results show that MKNN introduces smaller testing time than both KNN and weighted KNN.},

langid = {english},

keywords = {Cancer classification,Data mining,Gene expression,K-Nearest Neighbor,Microarray data classification}

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},

pages = {1415--1425},

issn = {1554-8627},

doi = {10.4161/auto.29165},

abstract = {Autophagy is a lysosomal degradation process that may act as a mechanism of survival in a variety of cancers. While pharmacologic inhibition of autophagy with hydroxychloroquine (HCQ) is currently being explored in human clinical trials, it has never been evaluated in canine cancers. Non-Hodgkin lymphoma (NHL) is one of the most prevalent tumor types in dogs and has similar pathogenesis and response to treatment as human NHL. Clinical trials in canine patients are conducted in the same way as in human patients, thus, to determine a maximum dose of HCQ that can be combined with a standard chemotherapy, a Phase I, single arm, dose escalation trial was conducted in dogs with spontaneous NHL presenting as patients to an academic, tertiary-care veterinary teaching hospital. HCQ was administered daily by mouth throughout the trial, beginning 72 h prior to doxorubicin (DOX), which was given intravenously on a 21-d cycle. Peripheral blood mononuclear cells and biopsies were collected before and 3 d after HCQ treatment and assessed for autophagy inhibition and HCQ concentration. A total of 30 patients were enrolled in the trial. HCQ alone was well tolerated with only mild lethargy and gastrointestinal-related adverse events. The overall response rate (ORR) for dogs with lymphoma was 93.3\%, with median progression-free interval (PFI) of 5 mo. Pharmacokinetic analysis revealed a 100-fold increase in HCQ in tumors compared with plasma. There was a trend that supported therapy-induced increase in LC3-II (the cleaved and lipidated form of microtubule-associated protein 1 light chain 3/LC3, which serves as a maker for autophagosomes) and SQSTM1/p62 (sequestosome 1) after treatment. The superior ORR and comparable PFI to single-agent DOX provide strong support for further evaluation via randomized, placebo-controlled trials in canine and human NHL.},

pmcid = {PMC4203518}

}

publisher = {Public Library of Science},

issn = {1932-6203},

doi = {10.1371/journal.pone.0102711},

abstract = {Four-stranded G-quadruplex DNA secondary structures have recently been visualized in the nuclei of human cultured cells. Here, we show that BG4, a G-quadruplex-specific antibody, can be used to stain DNA G-quadruplex structures in patient-derived tissues using immunohistochemistry. We observe a significantly elevated number of G-quadruplex-positive nuclei in human cancers of the liver and stomach as compared to background non-neoplastic tissue. Our results suggest that G-quadruplex formation can be detected and measured in patient-derived material and that elevated G-quadruplex formation may be a characteristic of some cancers.},

langid = {english},

keywords = {Breast cancer,Cell staining,DNA structure,Gastric cancer,Hepatocellular carcinoma,Immunohistochemistry techniques,Nuclear staining,Stomach}

publisher = {Elsevier},

issn = {0092-8674, 1097-4172},

doi = {10.1016/j.cell.2018.03.059},

langid = {english}

}

pages = {423--425},

issn = {1367-4803},

doi = {10.1093/bioinformatics/btr670},

abstract = {Abstract. Summary: More and more cancer studies use next-generation sequencing (NGS) data to detect various types of genomic variation. However, even when rese},

langid = {english}

}

date = {2012-06-01},

publisher = {Zenodo},

doi = {10.5281/zenodo.5706412},

abstract = {MINSEQE~describes the~Minimum Information about a high-throughput nucleotide SEQuencing Experiment~that is needed to enable the unambiguous interpretation and facilitate reproduction of the results of the~experiment. By analogy to the~MIAME~guidelines for microarray experiments, adherence to the MINSEQE guidelines will improve~integration of multiple experiments across different modalities, thereby maximising the value of high-throughput research.~ The five elements of experimental description considered essential when making data available supporting published high-throughput sequencing experiments are as follows: The description of the biological system, samples, and the experimental variables being studied: “compound” and “dose” in dose-response experiments or “antibody” in ChIP-Seq experiments,~the organism, tissue, and the ~treatment(s) applied. The sequence read data for each assay: read sequences and base-level quality scores for each assay;~FASTQ~format is recommended, with a description of the scale used for quality scores. The ‘final’ processed (or summary) data for the set of assays in the study: the data on which the conclusions in the related publication are based, and~descriptions of the data format. General information about the experiment and sample-data relationships: a summary of the experiment and its goals, contact information, any associated publication, and a~table specifying sample-data relationships. Essential experimental and data processing protocols: how the nucleic acid samples were isolated, purified and processed prior to sequencing,~a summary of the instrumentation used, library preparation strategy, labelling and amplification methodologies, alignment algorithms and data filtering plus data processing \& analysis protocols. The present document contains version 1.0 of the MINSEQE guidelines, which~originated from discussions at an FGED-organized workshop held in Berkeley in March 2008.},

langid = {english},

keywords = {nucleotide sequencing genome transcriptome genomics transcriptomics reproducibility standards publication}

pages = {145--154},

issn = {1573-6849},

doi = {10.1007/s10577-007-1212-4},

abstract = {The pathophysiological similarities shared by many forms of human and canine disease, combined with the sophisticated genomic resources now available for the dog, have placed ‘man’s best friend’ in a position of high visibility as a model system for a variety of biomedical concerns, including cancer. The importance of nonrandom cytogenetic abnormalities in human leukemia and lymphoma was recognized over 40~years ago, but the mechanisms of genome reorganization remain incompletely understood. The development of molecular cytogenetics, using fluorescence in situ hybridization (FISH) technology, has played a significant role in our understanding of cancer biology by providing a means for ‘interrogating’ tumor cells for a variety of gross genetic changes in the form of either numerical or structural chromosome aberrations. Here, we have identified cytogenetic abnormalities in naturally occurring canine hematopoietic tumors that are evolutionarily conserved compared with those that are considered characteristic of the corresponding human condition. These data suggest that humans and dogs share an ancestrally retained pathogenetic basis for cancer and that cytogenetic evaluation of canine tumors may provide greater insight into the biology of tumorigenesis.},

langid = {english}

}

pages = {453-465.e9},

issn = {1535-6108, 1878-3686},

doi = {10.1016/j.ccell.2018.08.006},

langid = {english},

keywords = {B cell,germinal center,lymphoma,MEF2B,mouse model}

}

publisher = {Public Library of Science},

issn = {1932-6203},

doi = {10.1371/journal.pone.0087361},

abstract = {Although recurrent somatic mutations in the splicing factor U2AF1 (also known as U2AF35) have been identified in multiple cancer types, the effects of these mutations on the cancer transcriptome have yet to be fully elucidated. Here, we identified splicing alterations associated with U2AF1 mutations across distinct cancers using DNA and RNA sequencing data from The Cancer Genome Atlas (TCGA). Using RNA-Seq data from 182 lung adenocarcinomas and 167 acute myeloid leukemias (AML), in which U2AF1 is somatically mutated in 3–4\% of cases, we identified 131 and 369 splicing alterations, respectively, that were significantly associated with U2AF1 mutation. Of these, 30 splicing alterations were statistically significant in both lung adenocarcinoma and AML, including three genes in the Cancer Gene Census, CTNNB1, CHCHD7, and PICALM. Cell line experiments expressing U2AF1 S34F in HeLa cells and in 293T cells provide further support that these altered splicing events are caused by U2AF1 mutation. Consistent with the function of U2AF1 in 3′ splice site recognition, we found that S34F/Y mutations cause preferences for CAG over UAG 3′ splice site sequences. This report demonstrates consistent effects of U2AF1 mutation on splicing in distinct cancer cell types.},

langid = {english},

keywords = {Acute myeloid leukemia,Adenocarcinoma,Adenocarcinoma of the lung,Alternative splicing,HeLa cells,Lung and intrathoracic tumors,Mutation,Somatic mutation}

pages = {54},

issn = {1741-7007},

doi = {10.1186/s12915-016-0279-9},

abstract = {Many pathogenic genetic variants have been shown to disrupt mRNA splicing. Besides splice mutations in the well-conserved splice sites, mutations in splicing regulatory elements (SREs) may deregulate splicing and cause disease. A promising therapeutic approach is to compensate for this deregulation by blocking other SREs with splice-switching oligonucleotides (SSOs). However, the location and sequence of most SREs are not well known.},

keywords = {Alternative splicing,Cross-linking immunoprecipitation (CLIP),hnRNP A1,iCLIP,Pseudoexons,RNA-seq,Splicing silencer,Splicing splice-switching oligonucleotides (SSOs),Surface plasmon resonance imaging (SPRi)}

}

pages = {339--346},

issn = {0952-7915},

doi = {10.1016/j.coi.2013.05.003},

abstract = {The BCL6 oncogenic repressor is a master regulator of humoral immunity and B-cell lymphoma survival. Whereas much research has focused on its regulation and function in germinal center B-cells, its role in other mature lymphoid cell compartments is less clear. A novel role for BCL6 in follicular T helper cell development was recently uncovered. The latest discoveries reveal that BCL6 is also an important regulator of other specialized helper T-cell subsets within germinal centers, pre-germinal center events, and peripheral T-cells effector functions. Here, we review newly discovered roles for BCL6 in lymphocyte subsets residing within and outside of germinal centers, and discuss their implications with respect to the molecular mechanisms of BCL6 regulation and potential links to B and T-cell lymphomas.},

pmcid = {PMC4075446}

}

pages = {239--244},

issn = {0952-7915},

doi = {10.1016/S0952-7915(97)80142-2},

abstract = {The initial phases of B cell development depend on interactions between the cell surface molecules and secreted products of stromal cells with their receptor-ligand partners on lymphoid progenitors. Recent research in this area has greatly advanced our understanding of B cell development and differentiation. Antigen receptors on pre-B and B cells play key roles in the progression of this differentiation process, as revealed by targeted and inherited gene mutations that disrupt B cell development and by the transgenic repair of these mutations in mice.},

langid = {english}

}

publisher = {American Association for Cancer Research},

issn = {1078-0432, 1557-3265},

doi = {10.1158/1078-0432.CCR-18-1498},

abstract = {Purpose: Only one chemical class of topoisomerase I (TOP1) inhibitors is FDA approved, the camptothecins with irinotecan and topotecan widely used. Because of their limitations (chemical instability, drug efflux-mediated resistance, and diarrhea), novel TOP1 inhibitors are warranted. Indenoisoquinoline non-camptothecin topoisomerase I (TOP1) inhibitors overcome chemical instability and drug resistance that limit camptothecin use. Three indenoisoquinolines, LMP400 (indotecan), LMP776 (indimitecan), and LMP744, were examined in a phase I study for lymphoma-bearing dogs to evaluate differential efficacy, pharmacodynamics, toxicology, and pharmacokinetics. Experimental Design: Eighty-four client-owned dogs with lymphomas were enrolled in dose-escalation cohorts for each indenoisoquinoline, with an expansion phase for LMP744. Efficacy, tolerability, pharmacokinetics, and target engagement were determined. Results: The MTDs were 17.5 mg/m2 for LMP 776 and 100 mg/m2 for LMP744; bone marrow toxicity was dose-limiting; up to 65 mg/m2 LMP400 was well-tolerated and MTD was not reached. None of the drugs induced notable diarrhea. Sustained tumor accumulation was observed for LMP744; γH2AX induction was demonstrated in tumors 2 and 6 hours after treatment; a decrease in TOP1 protein was observed in most lymphoma samples across all compounds and dose levels, which is consistent with the fact that tumor response was also observed at low doses LMP744. Objective responses were documented for all indenoisoquinolines; efficacy (13/19 dogs) was greatest for LMP744. Conclusions: These results demonstrate proof-of-mechanism for indenoisoquinoline TOP1 inhibitors supporting their further clinical development. They also highlight the value of the NCI Comparative Oncology Program (https://ccr.cancer.gov/Comparative-Oncology-Program) for evaluating novel therapies in immunocompetent pets with cancers.},

langid = {english}

}

pages = {611--622},

issn = {0009-9147},

doi = {10.1373/clinchem.2008.112797},

abstract = {Background: Currently, a lack of consensus exists on how best to perform and interpret quantitative real-time PCR (qPCR) experiments. The problem is exacerbated by a lack of sufficient experimental detail in many publications, which impedes a reader’s ability to evaluate critically the quality of the results presented or to repeat the experiments.Content: The Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines target the reliability of results to help ensure the integrity of the scientific literature, promote consistency between laboratories, and increase experimental transparency. MIQE is a set of guidelines that describe the minimum information necessary for evaluating qPCR experiments. Included is a checklist to accompany the initial submission of a manuscript to the publisher. By providing all relevant experimental conditions and assay characteristics, reviewers can assess the validity of the protocols used. Full disclosure of all reagents, sequences, and analysis methods is necessary to enable other investigators to reproduce results. MIQE details should be published either in abbreviated form or as an online supplement.Summary: Following these guidelines will encourage better experimental practice, allowing more reliable and unequivocal interpretation of qPCR results.}

}

pages = {623--637},

issn = {1535-6108},

doi = {10.1016/j.ccell.2015.09.009},

abstract = {In normal cells p53 is activated by DNA damage checkpoint kinases to simultaneously control the G1/S and G2/M cell cycle checkpoints through transcriptional induction of p21cip1 and Gadd45α. In p53 mutant tumors, cell cycle checkpoints are rewired, leading to dependency on the p38/MK2 pathway to survive DNA-damaging chemotherapy. Here we show that the RNA binding protein hnRNPA0 is the “successor” to p53 for checkpoint control. Like p53, hnRNPA0 is activated by a checkpoint kinase (MK2) and simultaneously controls both cell cycle checkpoints through distinct target mRNAs, but unlike p53 this is through the post-transcriptional stabilization of p27Kip1 and Gadd45α mRNAs. This pathway drives cisplatin resistance in lung cancer demonstrating the importance of post-transcriptional RNA control to chemotherapy response.,},

pmcid = {PMC4830093}

}