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

Morin, Ryan D., Mendez-Lago, Maria, Mungall, Andrew J., Goya, Rodrigo, Mungall, Karen L., Corbett, Richard D., Johnson, Nathalie A., Severson, Tesa M., Chiu, Readman, Field, Matthew, Jackman, Shaun, Krzywinski, Martin, Scott, David W., Trinh, Diane L., Tamura-Wells, Jessica, Li, Sa, Firme, Marlo R., Rogic, Sanja, Griffith, Malachi, Chan, Susanna, Yakovenko, Oleksandr, Meyer, Irmtraud M., Zhao, Eric Y., Smailus, Duane, Moksa, Michelle, Chittaranjan, Suganthi, Rimsza, Lisa, Brooks-Wilson, Angela, Spinelli, John J., Ben-Neriah, Susana, Meissner, Barbara, Woolcock, Bruce, Boyle, Merrill, McDonald, Helen, Tam, Angela, Zhao, Yongjun, Delaney, Allen, Zeng, Thomas, Tse, Kane, Butterfield, Yaron, Birol, Inanç, Holt, Rob, Schein, Jacqueline, Horsman, Douglas E., Moore, Richard, Jones, Steven J.M., Connors, Joseph M., Hirst, Martin, Gascoyne, Randy D., and Marra, Marco A. (2011) Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma. Nature, 476 (7360). pp. 298-303.

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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.

Item ID: 43192
Item Type: Article (Research - C1)
ISSN: 1476-4687
Keywords: H3K27; H3K4; HDAC; HAT; cancer genomics; methylation; acetylation; EZH2; driver; cancer sequencing
Additional Information:

This article is distributed under the terms of the Creative Commons Attribution-Non-Commercial-Share Alike licence (http://creativecommons.org/licenses/by-nc-sa/3.0/), which permits distribution, and reproduction in any medium, provided the original author and source are credited. This licence does not permit commercial exploitation, and derivative works must be licensed under the same or similar licence.

Funders: National Cancer Institute Office of Cancer Genomics (NCIOCG), Terry Fox Foundation (TFF), Genome Canada (GC), Genome British Columbia (GBC), National Institutes of Health (NIH), Leukemia and Lymphoma Society (LLS), Michael Smith Foundation for Health Research (MSFHR), Spanish Ministry of Education (SME), Canadian Cancer Society (CCS), Canadian Institutes of Health Research (CIHR), University of British Columbia (UBC), Canadian Foundation for Innovation for a Leaders Opportunity Fund (CFILOF)
Projects and Grants: NCIOCG Contract No. HHSN261200800001E, TFF grant 019001, Biology of Cancer: Insights from Genomic Analyses of Lymphoid Neoplasms, GC/GBC Grant Competition III (Project Title: High Resolution Analysis of Follicular Lymphoma Genomes), NIH P50CA130805-01, NIH 1U01CA114778 , TFF award NCIC 019005, MSFHR ST-PDF-01793, SME Programa Nacional de Movilidad de Recursos Humanos del Plan Nacional de I-D+ i 2008-2011, TFF at Canadian Institutes of Health Research Grant No. TGT-53912
Date Deposited: 12 Sep 2016 00:12
FoR Codes: 06 BIOLOGICAL SCIENCES > 0601 Biochemistry and Cell Biology > 060102 Bioinformatics @ 25%
06 BIOLOGICAL SCIENCES > 0604 Genetics > 060408 Genomics @ 25%
11 MEDICAL AND HEALTH SCIENCES > 1112 Oncology and Carcinogenesis > 111203 Cancer Genetics @ 50%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920102 Cancer and Related Disorders @ 50%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 50%
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