85 results match your criteria transcription mef2b


Unique Immune Cell Coactivators Specify Locus Control Region Function and Cell Stage.

Mol Cell 2020 12 23;80(5):845-861.e10. Epub 2020 Nov 23.

Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, NY 10065, USA. Electronic address:

Locus control region (LCR) functions define cellular identity and have critical roles in diseases such as cancer, although the hierarchy of structural components and associated factors that drive functionality are incompletely understood. Here we show that OCA-B, a B cell-specific coactivator essential for germinal center (GC) formation, forms a ternary complex with the lymphoid-enriched OCT2 and GC-specific MEF2B transcription factors and that this complex occupies and activates an LCR that regulates the BCL6 proto-oncogene and is uniquely required by normal and malignant GC B cells. Mechanistically, through OCA-B-MED1 interactions, this complex is required for Mediator association with the BCL6 promoter. Read More

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December 2020

Landscape of DNA binding signatures of myocyte enhancer factor-2B reveals a unique interplay of base and shape readout.

Nucleic Acids Res 2020 09;48(15):8529-8544

Quantitative and Computational Biology, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.

Myocyte enhancer factor-2B (MEF2B) has the unique capability of binding to its DNA target sites with a degenerate motif, while still functioning as a gene-specific transcriptional regulator. Identifying its DNA targets is crucial given regulatory roles exerted by members of the MEF2 family and MEF2B's involvement in B-cell lymphoma. Analyzing structural data and SELEX-seq experimental results, we deduced the DNA sequence and shape determinants of MEF2B target sites on a high-throughput basis in vitro for wild-type and mutant proteins. Read More

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September 2020

Crystal Structures of Ternary Complexes of MEF2 and NKX2-5 Bound to DNA Reveal a Disease Related Protein-Protein Interaction Interface.

J Mol Biol 2020 09 15;432(19):5499-5508. Epub 2020 Jul 15.

Molecular and Computational Biology, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA; Department of Chemistry, University of Southern California, Los Angeles, CA 90089, USA; USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA. Electronic address:

MEF2 and NKX2-5 transcription factors interact with each other in cardiogenesis and are necessary for normal heart formation. Despite evidence suggesting that these two transcription factors function synergistically and possibly through direct physical interactions, molecular mechanisms by which they interact are not clear. Here we determined the crystal structures of ternary complexes of MEF2 and NKX2-5 bound to myocardin enhancer DNA in two crystal forms. Read More

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September 2020

In Silico Exploration of Conformational Dynamics and Novel Inhibitors for Targeting MEF2-Associated Transcriptional Activity.

J Chem Inf Model 2020 03 7;60(3):1892-1909. Epub 2020 Feb 7.

National Center for Bioinformatics, Quaid-i-Azam University, 45320 Islamabad, Pakistan.

Myocyte enhancer factor 2 (MEF2; MEF2A-MEF2D) transcription factors regulate gene expression in a variety of developmental processes by binding to AT-rich DNA motifs via highly conserved N-terminal extensions known as MADS-box and MEF2 domains. Despite the fact that MEF2 proteins exhibit high similarity at their N-terminal regions and share a common consensus DNA binding motif, their functional preferences may vary significantly in the adjacent regions to the DNA binding core segment. The current study delineates the conformational paradigm, clustered recognition, and comparative DNA binding preferences for MEF2A and MEF2B-specific MADS-box/MEF2 domains at the YTA(A/T)4TAR consensus motif. Read More

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Combined burden and functional impact tests for cancer driver discovery using DriverPower.

Nat Commun 2020 02 5;11(1):734. Epub 2020 Feb 5.

Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada, M5S 1A8.

The discovery of driver mutations is one of the key motivations for cancer genome sequencing. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumour types, we describe DriverPower, a software package that uses mutational burden and functional impact evidence to identify driver mutations in coding and non-coding sites within cancer whole genomes. Using a total of 1373 genomic features derived from public sources, DriverPower's background mutation model explains up to 93% of the regional variance in the mutation rate across multiple tumour types. Read More

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February 2020

[Expression of myocyte enhancer factor 2B in mantle cell lymphoma and its clinical significance].

Zhonghua Bing Li Xue Za Zhi 2020 Jan;49(1):40-46

Department of Pathology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.

To investigate the expression of myocyte enhancer factor 2B (MEF2B) in mantle cell lymphomas (MCL), and to analyze the correlation between the expression of MEF2B and pathological subtypes, structural subtypes, SOX11 expression and its clinical significance. Paraffin-embedded tissues were stained with HE, immunohistochemistry (EnVision method) and fluorescence in situ hybridization (FISH) , in addition, the clinical and pathological data of 60 cases of MCL were collected at Sun Yat-sen University Foshan Hospital and Sun Yat-sen University Cancer Center from January,2002 to May, 2019 for analysis. Of the 60 MCLs, males is predominant (M∶F3∶1). Read More

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January 2020

Transcription factor binding at Ig enhancers is linked to somatic hypermutation targeting.

Eur J Immunol 2020 03 19;50(3):380-395. Epub 2019 Dec 19.

Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.

Secondary diversification of the Ig repertoire occurs through somatic hypermutation (SHM), gene conversion (GCV), and class switch recombination (CSR)-three processes that are initiated by activation-induced cytidine deaminase (AID). AID targets Ig genes at orders of magnitude higher than the rest of the genome, but the basis for this specificity is poorly understood. We have previously demonstrated that enhancers and enhancer-like sequences from Ig genes are capable of stimulating SHM of neighboring genes in a capacity distinct from their roles in increasing transcription. Read More

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Common Carp Genes: Evolution and Expression.

Genes (Basel) 2019 08 1;10(8). Epub 2019 Aug 1.

National and Local Joint Engineering Laboratory for Freshwater Fish Breeding, Heilongjiang River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Harbin 150070, China.

The MEF2 (myocyte enhancer factor 2) family belongs to the MADS-box superfamily of eukaryotic transcription factors. The vertebrate genes compose four distinct subfamilies designated MEF2A, -B, -C, and -D. There are multiple mef2 genes in the common carp (). Read More

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Convergent Evidence From Humans and Drosophila melanogaster Implicates the Transcription Factor MEF2B/Mef2 in Alcohol Sensitivity.

Alcohol Clin Exp Res 2019 09 16;43(9):1872-1886. Epub 2019 Jul 16.

Human Genetics Ph.D. Program, Virginia Commonwealth University, Richmond, Virginia.

Background: Self-Rating of the Effects of Alcohol (SRE) measures level of response to ethanol (EtOH) in humans. Interestingly, there is a positive relationship between the SRE and risk for abusing alcohol, suggesting mechanistic connections between SRE and alcohol abuse.

Methods: To identify candidate genes with a role in SRE and alcohol-related behavior more generally, we coupled human genetic analyses with studies in Drosophila melanogaster. Read More

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September 2019

Akirin1 promotes myoblast differentiation by modulating multiple myoblast differentiation factors.

Biosci Rep 2019 03 1;39(3). Epub 2019 Mar 1.

Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Ya'an 625014, Sichuan, P.R. China

Akirin1 is found to be involved in myoblast differentiation. However, the mechanism by which the Akirin1 gene regulates myoblast differentiation still remains unclear. In the present study, we found that ectopic expression of Akirin1 promoted myoblast differentiation by increasing the expression of myogenic regulatory factor (MRF) 4 () and myocyte enhancer factor 2B () mRNA. Read More

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MEF2 plays a significant role in the tumor inhibitory mechanism of encapsulated RENCA cells via EGF receptor signaling in target tumor cells.

BMC Cancer 2018 Dec 4;18(1):1217. Epub 2018 Dec 4.

The Rogosin Institute-Xenia Division, 740 Birch Road, Xenia, OH, 45385, USA.

Background: Agarose encapsulated murine renal adenocarcinoma cells (RENCA macrobeads) are currently being investigated in clinical trials as a treatment for therapy-resistant metastatic colorectal cancer. We have previously demonstrated the capacity of RENCA macrobeads to produce diffusible substances that markedly inhibit the proliferation of epithelial-derived tumor cells outside the macrobead environment. This study examined the molecular mechanisms underlying the observed inhibition in targeted tumor cells exposed to RENCA macrobeads. Read More

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December 2018

MEF2B is a member of the BCL6 gene transcriptional complex and induces its expression in diffuse large B-cell lymphoma of the germinal center B-cell-like type.

Lab Invest 2019 04 16;99(4):539-550. Epub 2018 Nov 16.

Department of Surgery, Tulane University School of Medicine, New Orleans, LA, USA.

Myocyte enhancer-binding factor 2B (MEF2B) has been implicated as a transcriptional regulator for BCL6. However, details about the interaction between MEF2B and BCL6 during expression, as well as the relationship of MEF2B to the expression of other germinal center (GC) markers, have not yet been fully explained. Using germinal center B-cell-like diffuse large B-cell lymphoma (GC-DLBCL) and activated B-cell diffuse large B-cell lymphoma (ABC-DLBCL) cell lines, we analyzed the expression of MEF2B and its associations with BCL6, CD10, and ERK. Read More

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MEF2B Instructs Germinal Center Development and Acts as an Oncogene in B Cell Lymphomagenesis.

Cancer Cell 2018 09;34(3):453-465.e9

Institute for Cancer Genetics, Columbia University, New York, NY 10032, USA; Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA; Department of Microbiology and Immunology, Columbia University, New York, NY 10032, USA; Department of Genetics and Development, Columbia University, New York, NY 10032, USA; The Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY 10032, USA. Electronic address:

The gene encoding the MEF2B transcription factor is mutated in germinal center (GC)-derived B cell lymphomas, but its role in GC development and lymphomagenesis is unknown. We demonstrate that Mef2b deletion reduces GC formation in mice and identify MEF2B transcriptional targets in GC, with roles in cell proliferation, apoptosis, GC confinement, and differentiation. The most common lymphoma-associated MEF2B mutant (MEF2B) is hypomorphic, yet escapes binding and negative regulation by components of the HUCA complex and class IIa HDACs. Read More

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September 2018

Direct Reprogramming of Fibroblasts Into Smooth Muscle-Like Cells With Defined Transcription Factors-Brief Report.

Arterioscler Thromb Vasc Biol 2018 09;38(9):2191-2197

From the Division of Cardiovascular Medicine, Department of Internal Medicine (H.H., M.T.G.-B., O.R., J.Z., Y.E.C.).

Objective- To identify the transcription factors that could contribute to direct reprogramming of fibroblasts toward smooth muscle cell fate. Approach and Results- We screened various combinations of transcription factors, including Myocd (myocardin), Mef2C (myocyte enhancer factor 2C), Mef2B (myocyte enhancer factor 2B), Mkl1 (MKL [megakaryoblastic leukemia]/Myocd-like 1), Gata4 (GATA-binding protein 4), Gata5 (GATA-binding protein 5), Gata6 (GATA-binding protein 6), Ets1 (E26 avian leukemia oncogene 1, 5' domain), and their corresponding carboxyterminal fusions to the transactivation domain of MyoD (myogenic differentiation 1)-indicated by *-for their effects on reprogramming mouse embryonic fibroblasts and human adult dermal fibroblasts to the smooth muscle cell fate as determined by the expression of specific markers. The combination of 3 transcription factors, Myocd (or Myocd*) with Mef2C (or Mef2C*) and Gata6, was the most efficient in enhancing the expression of smooth muscle marker genes and decreasing fibroblast gene expression. Read More

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September 2018

Crystal Structure of Apo MEF2B Reveals New Insights in DNA Binding and Cofactor Interaction.

Biochemistry 2018 07 5;57(28):4047-4051. Epub 2018 Jul 5.

Molecular and Computational Biology, Department of Biological Sciences , University of Southern California , Los Angeles , California 90089 , United States.

The myocyte enhancer factor 2 (MEF2) family of transcription factors plays important roles in developmental processes and adaptive responses. Although MEF2 proteins are known to bind DNA in the nucleus to regulate specific gene expression, there are reports that show that MEF2 also functions in the cytoplasm. Previous structural studies of MEF2 focused exclusively on DNA-bound MEF2 with and without various corepressors or coactivators. Read More

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MEF2 and the tumorigenic process, hic sunt leones.

Biochim Biophys Acta Rev Cancer 2018 12 5;1870(2):261-273. Epub 2018 Jun 5.

Department of Medicine, Università degli Studi di Udine, P.le Kolbe 4, 33100 Udine, Italy. Electronic address:

While MEF2 transcription factors are well known to cooperate in orchestrating cell fate and adaptive responses during development and adult life, additional studies over the last decade have identified a wide spectrum of genetic alterations of MEF2 in different cancers. The consequences of these alterations, including triggering and maintaining the tumorigenic process, are not entirely clear. A deeper knowledge of the molecular pathways that regulate MEF2 expression and function, as well as the nature and consequences of MEF2 mutations are necessary to fully understand the many roles of MEF2 in malignant cells. Read More

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December 2018

A kinome-wide high-content siRNA screen identifies MEK5-ERK5 signaling as critical for breast cancer cell EMT and metastasis.

Oncogene 2018 08 1;37(31):4197-4213. Epub 2018 May 1.

Department of Biomedicine, University of Basel, Basel, 4058, Switzerland.

An epithelial to mesenchymal transition (EMT) has been correlated to malignant tumor progression and metastasis by promoting cancer cell migration and invasion and chemoresistance. Hence, finding druggable EMT effectors is critical to efficiently interfere with metastasis formation and to overcome therapy resistance. We have employed a high-content microscopy screen in combination with a kinome and phosphatome-wide siRNA library to identify signaling pathways underlying an EMT of murine mammary epithelial cells and breast cancer cells. Read More

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The Cancer Mutation D83V Induces an α-Helix to β-Strand Conformation Switch in MEF2B.

J Mol Biol 2018 04 22;430(8):1157-1172. Epub 2018 Feb 22.

Molecular and Computational Biology, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA; Department of Chemistry, University of Southern California, Los Angeles, CA 90089, USA; USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA. Electronic address:

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. Read More

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Comparison of Myocyte Enhancer Factor 2B Versus Other Germinal Center-associated Antigens in the Differential Diagnosis of B-Cell Non-Hodgkin Lymphomas.

Am J Surg Pathol 2018 03;42(3):342-350

University of Pittsburgh School of Medicine, Pittsburgh, PA.

Myocyte enhancer binding factor 2B (MEF2B) is a transcriptional activator of the BCL6 proto-oncogene in normal germinal center (GC) B-cells. Limited data exists concerning its expression in B-cell lymphomas, and comparison with other GC-associated antigens is lacking. Its role in the differential diagnosis of B-cell lymphomas, particularly in the distinction of follicular lymphoma (FL) versus marginal zone lymphoma (MZL), remains to be determined. Read More

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MEF2 transcription factors in human placenta and involvement in cytotrophoblast invasion and differentiation.

Physiol Genomics 2018 01 10;50(1):10-19. Epub 2017 Nov 10.

Department of Pediatrics, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, Texas.

Development of the human placenta and its trophoblast cell types is critical for a successful pregnancy. Defects in trophoblast invasion and differentiation are associated with adverse pregnancy outcomes, including preeclampsia. The members of myocyte enhancer factor-2 (MEF2) family of transcription factors are key regulators of cellular proliferation, differentiation, and invasion in various cell types and tissues and might play a similarly important role in regulating trophoblast proliferation, invasion, and differentiation during human placental development. Read More

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January 2018

FOXP1 expression is a prognostic biomarker in follicular lymphoma treated with rituximab and chemotherapy.

Blood 2018 01 9;131(2):226-235. Epub 2017 Nov 9.

Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre-University Health Network, Toronto, ON, Canada.

Follicular lymphoma (FL) is a clinically and molecularly highly heterogeneous disease, yet prognostication relies predominantly on clinical tools. We recently demonstrated that integration of mutation status of 7 genes, including and improves risk stratification. We mined gene expression data to uncover genes that are differentially expressed in - and -mutated cases. Read More

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January 2018

J chain and myocyte enhancer factor 2B are useful in differentiating classical Hodgkin lymphoma from nodular lymphocyte predominant Hodgkin lymphoma and primary mediastinal large B-cell lymphoma.

Hum Pathol 2017 10 26;68:47-53. Epub 2017 Aug 26.

University of Pittsburgh School of Medicine, Pittsburgh, PA 15213. Electronic address:

Although most classical Hodgkin lymphomas (CHLs) are easily distinguished from nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) and primary mediastinal large B-cell lymphoma (PMBL), cases with significant CD20 expression cause diagnostic confusion. Although the absence of OCT-2 and BOB.1 are useful in these circumstances, a variable proportion of CHLs are positive for these antigens. Read More

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October 2017

Direct reprogramming of fibroblasts into skeletal muscle progenitor cells by transcription factors enriched in undifferentiated subpopulation of satellite cells.

Sci Rep 2017 08 14;7(1):8097. Epub 2017 Aug 14.

Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, 187-8502, Japan.

Satellite cells comprise a functionally heterogeneous population of stem cells in skeletal muscle. Separation of an undifferentiated subpopulation and elucidation of its molecular background are necessary to identify the reprogramming factors to induce skeletal muscle progenitor cells. In this study, we found that intracellular esterase activity distinguishes a subpopulation of cultured satellite cells with high stemness using esterase-sensitive cell staining reagent, calcein-AM. Read More

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Whole genome sequence study of cannabis dependence in two independent cohorts.

Addict Biol 2018 01 23;23(1):461-473. Epub 2017 Jan 23.

Departments of Neurology and Genetics, University of North Carolina, Chapel Hill, NC, USA.

Recent advances in genome wide sequencing techniques and analytical methods allow for more comprehensive examinations of the genome than microarray-based genome-wide association studies (GWAS). The present report provides the first application of whole genome sequencing (WGS) to identify low frequency variants involved in cannabis dependence across two independent cohorts. The present study used low-coverage whole genome sequence data to conduct set-based association and enrichment analyses of low frequency variation in protein-coding regions as well as regulatory regions in relation to cannabis dependence. Read More

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January 2018

DNA damage induced apoptosis suppressor (DDIAS) is upregulated via ERK5/MEF2B signaling and promotes β-catenin-mediated invasion.

Biochim Biophys Acta 2016 11 10;1859(11):1449-1458. Epub 2016 Jul 10.

Genomic Personalized Medicine Research Center, KRIBB, Daejeon 305-806, Republic of Korea; Functional Genomics, University of Science and Technology, Daejeon 305-701, Republic of Korea. Electronic address:

DNA damage induced apoptosis suppressor (DDIAS) is an anti-apoptotic protein that promotes cancer cell survival. We previously reported that DDIAS is transcriptionally activated by nuclear factor of activated T cells 2 (NFATc1). However, the upstream regulation of DDIAS expression by growth factors has not been studied. Read More

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November 2016

Data on the transcriptional regulation of DNA damage induced apoptosis suppressor (DDIAS) by ERK5/MEF2B pathway in lung cancer cells.

Data Brief 2016 Dec 6;9:257-61. Epub 2016 Sep 6.

Personalized Genomic Medicine Research Center, KRIBB, Daejeon 305-806, Korea; Functional Genomics, University of Science and Technology, Daejeon 305-701, Korea.

The data included in this article are associated with the article entitled "DNA-damage-induced apoptosis suppressor (DDIAS) is upregulated via ERK5/MEF2B signaling and promotes β-catenin-mediated invasion" (J.Y. Im, S. Read More

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December 2016

Identification of MEF2B and TRHDE Gene Polymorphisms Related to Growth Traits in a New Ujumqin Sheep Population.

PLoS One 2016 29;11(7):e0159504. Epub 2016 Jul 29.

Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China.

2 SNPs were discovered in our previous genome-wide association study (GWAS): s58995.1 (rs420767326 A>G) in MEF2B gene and OAR3_115712045.1 (rs401775061 A>C) in TRHDE gene, which were significantly associated with post-weaning gain in sheep. Read More

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Combined copy number and mutation analysis identifies oncogenic pathways associated with transformation of follicular lymphoma.

Leukemia 2017 01 16;31(1):83-91. Epub 2016 Jun 16.

Department of Pathology, City of Hope National Medical Center, Duarte, CA, USA.

Follicular lymphoma (FL) is typically an indolent disease, but 30-40% of FL cases transform into an aggressive lymphoma (tFL) with a poor prognosis. To identify the genetic changes that drive this transformation, we sequenced the exomes of 12 cases with paired FL and tFL biopsies and identified 45 recurrently mutated genes in the FL-tFL data set and 39 in the tFL cases. We selected 496 genes of potential importance in transformation and sequenced them in 23 additional tFL cases. Read More

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January 2017

Phase 2 study of panobinostat with or without rituximab in relapsed diffuse large B-cell lymphoma.

Blood 2016 07 10;128(2):185-94. Epub 2016 May 10.

Segal Cancer Center, Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada;

The majority of diffuse large B-cell lymphoma (DLBCL) tumors contain mutations in histone-modifying enzymes (HMEs), indicating a potential therapeutic benefit of histone deacetylase inhibitors (HDIs), and preclinical data suggest that HDIs augment the effect of rituximab. In this randomized phase 2 study, we evaluated the response rate and toxicity of panobinostat, a pan-HDI administered 30 mg orally 3 times weekly, with or without rituximab, in 40 patients with relapsed or refractory de novo (n = 27) or transformed (n = 13) DLBCL. Candidate genes and whole exomes were sequenced in relapse tumor biopsies to search for molecular correlates, and these data were used to quantify circulating tumor DNA (ctDNA) in serial plasma samples. Read More

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MEF2 transcription factors: developmental regulators and emerging cancer genes.

Oncotarget 2016 Jan;7(3):2297-312

Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, Canada.

The MEF2 transcription factors have roles in muscle, cardiac, skeletal, vascular, neural, blood and immune system cell development through their effects on cell differentiation, proliferation, apoptosis, migration, shape and metabolism. Altered MEF2 activity plays a role in human diseases and has recently been implicated in the development of several cancer types. In particular, MEF2B, the most divergent and least studied protein of the MEF2 family, has a role unique from its paralogs in non-Hodgkin lymphomas. Read More

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January 2016