updates

+---

+bibliography: 'morinlab.bib'

+csl: 'NLM.csl'

+link-citations: true

+---

+DUSP2 functions as a negative regulator of MAPK signaling, particularly affecting the ERK1/2 pathway.

+DUSP2 mutations have been reported in nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), T-cell/histiocyte-rich large B-cell lymphoma (T/HRLBCL)[@schuhmacherJUNBDUSP2SGK12019b; @hartmannHighlyRecurrentMutations2016b] and they are relatively frequent in DLBCL.

+DUSP2 is one of [a number of genes](https://github.com/morinlab/LLMPP/wiki/ashm) affected by aberrant somatic hypermutation in B-cell lymphomas, which complicates the interpretation of mutations at this locus.

+These mutations are associated with the ST2 genetic subgroup of DLBCL.

+This gene has some recurrent sites of mutations (hot spots).

+The mutation pattern in DLBCL implies the preferential accumulation of *inactivating mutations*.

+

+||1|high-confidence PMBL/cHL/GZL gene[@dunsCharacterizationDLBCLPMBL2021b]|

+| |1-a | aSHM target and high-confidence DLBCL gene [@morinMutationalStructuralAnalysis2013]|

+

+## References

+

+

+@article{hartmannHighlyRecurrentMutations2016b,

+ 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{schuhmacherJUNBDUSP2SGK12019b,

+ 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},

+ file = {/Users/rmorin/Zotero/storage/YU4PADF6/Schuhmacher et al. - 2019 - JUNB, DUSP2, SGK1, SOCS1 and CREBBP are frequently.pdf}

+}

+