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Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma

Item Type:Article
Title:Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma
Creators Name:Morin, R.D. and Mendez-Lago, M. and Mungall, A.J. and Goya, R. and Mungall, K.L. and Corbett, R.D. and Johnson, N.A. and Severson, T.M. and Chiu, R. and Field, M. and Jackman, S. and Krzywinski, M. and Scott, D.W. and Trinh, D.L. and Tamura-Wells, J. and Li, S. and Firme, M.R. and Rogic, S. and Griffith, M. and Chan, S. and Yakovenko, O. and Meyer, I.M. and Zhao, E.Y. and Smailus, D. and Moksa, M. and Chittaranjan, S. and Rimsza, L. and Brooks-Wilson, A. and Spinelli, J.J. and Ben-Neriah, S. and Meissner, B. and Woolcock, B. and Boyle, M. and McDonald, H. and Tam, A. and Zhao, Y. and Delaney, A. and Zeng, T. and Tse, K. and Butterfield, Y. and Birol, I. and Holt, R. and Schein, J. and Horsman, D.E. and Moore, R. and Jones, S.J.M. and Connors, J.M. and Hirst, M. and Gascoyne, R.D. and Marra, M.A.
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.
Keywords:Chromatin, DNA-Binding Proteins, Follicular Lymphoma, Histone Acetyltransferases, Histone-Lysine N-Methyltransferase, Histones, Human Genome, Large Diffuse B-Cell Lymphoma, Loss of Heterozygosity, MADS Domain Proteins, MEF2 Transcription Factors, Mutation, Myogenic Regulatory Factors, Neoplasm Proteins, Non-Hodgkin Lymphoma
Source:Nature
ISSN:0028-0836
Publisher:Nature Publishing Group (U.K.)
Volume:476
Number:7360
Page Range:298-303
Date:18 August 2011
Official Publication:https://doi.org/10.1038/nature10351
PubMed:View item in PubMed

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