1. Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma
- Author
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Michelle Moksa, Angela Tam, Readman Chiu, Kane Tse, Malachi Griffith, Sa Li, Karen Mungall, Eric Y. Zhao, Barbara Meissner, Shaun D. Jackman, Bruce Woolcock, Matthew A. Field, Susanna Chan, Merrill Boyle, Martin Hirst, David W. Scott, Susana Ben-Neriah, John J. Spinelli, Yaron S.N. Butterfield, Duane E. Smailus, Allen Delaney, Marco A. Marra, Yongjun Zhao, Oleksandr Yakovenko, Sanja Rogic, Angela Brooks-Wilson, Jessica Tamura-Wells, Nathalie A. Johnson, Diane L. Trinh, Randy D. Gascoyne, Irmtraud M. Meyer, Jacqueline E. Schein, Rodrigo Goya, Suganthi Chittaranjan, Robert A. Holt, Joseph M. Connors, Andrew J. Mungall, Ryan D. Morin, Steven J.M. Jones, Maria Mendez-Lago, Marlo Firme, Tesa M. Severson, Lisa M. Rimsza, Richard A. Moore, Helen McDonald, Martin Krzywinski, Douglas E. Horsman, Thomas Zeng, Inanc Birol, and Richard Corbett
- Subjects
Follicular lymphoma ,Loss of Heterozygosity ,medicine.disease_cause ,Histones ,Loss of heterozygosity ,0302 clinical medicine ,HDAC ,immune system diseases ,hemic and lymphatic diseases ,Lymphoma, Follicular ,Histone Acetyltransferases ,0303 health sciences ,Mutation ,Multidisciplinary ,biology ,MEF2 Transcription Factors ,Lymphoma, Non-Hodgkin ,Chromatin ,Neoplasm Proteins ,DNA-Binding Proteins ,cancer sequencing ,Histone ,Myogenic Regulatory Factors ,030220 oncology & carcinogenesis ,Histone methyltransferase ,Histone Methyltransferases ,Lymphoma, Large B-Cell, Diffuse ,driver ,MADS Domain Proteins ,Article ,H3K4 ,03 medical and health sciences ,Germline mutation ,medicine ,Humans ,EZH2 ,EP300 ,acetylation ,030304 developmental biology ,H3K27 ,cancer genomics ,Genome, Human ,Histone-Lysine N-Methyltransferase ,medicine.disease ,Molecular biology ,Lymphoma ,HAT ,biology.protein ,Cancer research ,methylation - 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.
- Published
- 2011
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