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

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.

• Authors: Ryan D Morin, Maria Mendez-Lago, Andrew J Mungall, Rodrigo Goya, Karen L Mungall, Richard D Corbett, Nathalie A Johnson, Tesa M Severson, Readman Chiu, Matthew Field, Shaun Jackman, Martin Krzywinski, David W Scott, Diane L Trinh, Jessica Tamura-Wells, Sa Li, Marlo R Firme, Sanja Rogic, Malachi Griffith, Susanna Chan, Oleksandr Yakovenko, Irmtraud M Meyer, Eric Y Zhao, Duane Smailus, Michelle Moksa, Suganthi Chittaranjan, Lisa Rimsza, Angela Brooks-Wilson, John J Spinelli, Susana Ben-Neriah, Barbara Meissner, Bruce Woolcock, Merrill Boyle, Helen McDonald, Angela Tam, Yongjun Zhao, Allen Delaney, Thomas Zeng, Kane Tse, Yaron Butterfield, Inanç Birol, Rob Holt, Jacqueline Schein, Douglas E Horsman, Richard Moore, Steven J M Jones, Joseph M Connors, Martin Hirst, Randy D Gascoyne, Marco A Marra
• Journal: Nature (Nature) Vol. 476 Issue 7360 Pg. 298-303 (Jul 27 2011) ISSN: 1476-4687 [Electronic] England
• PMID: 21796119 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Chromatin
• DNA-Binding Proteins
• Histones
• KMT2D protein, human
• MADS Domain Proteins
• MEF2 Transcription Factors
• MEF2B protein, human
• Myogenic Regulatory Factors
• Neoplasm Proteins
• Histone Methyltransferases
• Histone-Lysine N-Methyltransferase
• Histone Acetyltransferases

Topics

• Chromatin (genetics, metabolism)
• DNA-Binding Proteins (genetics, metabolism)
• Genome, Human (genetics)
• Histone Acetyltransferases (genetics, metabolism)
• Histone Methyltransferases
• Histone-Lysine N-Methyltransferase (genetics, metabolism)
• Histones (metabolism)
• Humans
• Loss of Heterozygosity (genetics)
• Lymphoma, Follicular (enzymology, genetics)
• Lymphoma, Large B-Cell, Diffuse (enzymology, genetics)
• Lymphoma, Non-Hodgkin (enzymology, genetics)
• MADS Domain Proteins (genetics, metabolism)
• MEF2 Transcription Factors
• Mutation (genetics)
• Myogenic Regulatory Factors (genetics, metabolism)
• Neoplasm Proteins (genetics, metabolism)