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

被引：1280

作者：

Morin, Ryan D. ^{[1
]}

Mendez-Lago, Maria ^{[1
]}

Mungall, Andrew J. ^{[1
]}

Goya, Rodrigo ^{[1
]}

Mungall, Karen L. ^{[1
]}

Corbett, Richard D. ^{[1
]}

Johnson, Nathalie A. ^{[2
]}

Severson, Tesa M. ^{[1
]}

Chiu, Readman ^{[1
]}

Field, Matthew ^{[1
]}

Jackman, Shaun ^{[1
]}

Krzywinski, Martin ^{[1
]}

Scott, David W. ^{[2
]}

Trinh, Diane L. ^{[1
]}

Tamura-Wells, Jessica ^{[1
]}

Li, Sa ^{[1
]}

Firme, Marlo R. ^{[1
]}

Rogic, Sanja ^{[2
]}

Griffith, Malachi ^{[1
]}

Chan, Susanna ^{[1
]}

Yakovenko, Oleksandr ^{[1
]}

Meyer, Irmtraud M. ^{[3
]}

Zhao, Eric Y. ^{[1
]}

Smailus, Duane ^{[1
]}

Moksa, Michelle ^{[1
]}

Chittaranjan, Suganthi ^{[1
]}

Rimsza, Lisa ^{[4
]}

Brooks-Wilson, Angela ^{[1
,5
]}

Spinelli, John J.

Ben-Neriah, Susana ^{[2
]}

Meissner, Barbara ^{[2
]}

Woolcock, Bruce ^{[2
]}

Boyle, Merrill ^{[2
]}

McDonald, Helen ^{[1
]}

Tam, Angela ^{[1
]}

Zhao, Yongjun ^{[1
]}

Delaney, Allen ^{[1
]}

Zeng, Thomas ^{[1
]}

Tse, Kane ^{[1
]}

Butterfield, Yaron ^{[1
]}

Birol, Inanc ^{[1
]}

Holt, Rob ^{[1
]}

Schein, Jacqueline ^{[1
]}

Horsman, Douglas E. ^{[2
]}

Moore, Richard ^{[1
]}

Jones, Steven J. M. ^{[1
]}

Connors, Joseph M. ^{[2
,6
]}

Hirst, Martin ^{[1
]}

Gascoyne, Randy D. ^{[2
,7
]}

Marra, Marco A. ^{[1
,8
]}

机构：

[1] BC Canc Agcy Vancouver, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada

[2] BC Canc Agcy, Ctr Lymphoid Canc, Vancouver, BC V5Z 1L3, Canada

[3] Centre High Throughput Biol, Dept Comp Sci, Vancouver, BC V6T 1Z4, Canada

[4] Univ Arizona, Dept Pathol, Tucson, AZ 85724 USA

[5] Simon Fraser Univ, Dept Biomed Physiol & Kinesiol, Burnaby, BC V5A 1S6, Canada

[6] Univ British Columbia, Sch Populat & Publ Hlth, Vancouver, BC V6T 1Z3, Canada

[7] Univ British Columbia, Dept Pathol, Vancouver, BC V6T 2B5, Canada

[8] Univ British Columbia, Dept Med Genet, Vancouver, BC V6H 3N1, Canada

来源：

NATURE | 2011年 / 476卷 / 7360期

基金：

加拿大健康研究院;

关键词：

B-CELL LYMPHOMA; NF-KAPPA-B; FOLLICULAR LYMPHOMA; SOMATIC MUTATIONS; RNA-SEQ; INACTIVATION; CANCER; EXPRESSION; SUBTYPES; PHOSPHORYLATION;

D O I：

10.1038/nature10351

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：298 / 303

页数：6