Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin

被引：1298

作者：

Morin, Ryan D. ^{[1
]}

Johnson, Nathalie A.

Severson, Tesa M. ^{[1
]}

Mungall, Andrew J. ^{[1
]}

An, Jianghong ^{[1
]}

Goya, Rodrigo ^{[1
]}

Paul, Jessica E. ^{[1
]}

Boyle, Merrill

Woolcock, Bruce W.

Kuchenbauer, Florian

Yap, Damian

Humphries, R. Keith

Griffith, Obi L. ^{[1
]}

Shah, Sohrab

Zhu, Henry ^{[2
]}

Kimbara, Michelle ^{[2
]}

Shashkin, Pavel ^{[2
]}

Charlot, Jean F. ^{[2
]}

Tcherpakov, Marianna ^{[2
]}

Corbett, Richard ^{[1
]}

Tam, Angela ^{[1
]}

Varhol, Richard ^{[1
]}

Smailus, Duane ^{[1
]}

Moksa, Michelle ^{[1
]}

Zhao, Yongjun ^{[1
]}

Delaney, Allen ^{[1
]}

Qian, Hong ^{[1
]}

Birol, Inanc ^{[1
]}

Schein, Jacqueline ^{[1
]}

Moore, Richard ^{[1
]}

Holt, Robert ^{[1
]}

Horsman, Doug E. ^{[3
]}

Connors, Joseph M. ^{[4
]}

Jones, Steven ^{[1
]}

Aparicio, Samuel

Hirst, Martin ^{[1
]}

Gascoyne, Randy D. ^{[3
]}

Marra, Marco A. ^{[1
,5
]}

机构：

[1] BC Canc Agcy, Genome Sci Ctr, Vancouver, BC, Canada

[2] BPS Biosci, San Diego, CA USA

[3] Univ British Columbia, Dept Pathol, Vancouver, BC, Canada

[4] Univ British Columbia, Div Med Oncol, Vancouver, BC V5Z 1M9, Canada

[5] Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada

来源：

NATURE GENETICS | 2010年 / 42卷 / 02期

基金：

美国国家卫生研究院;

关键词：

GROUP PROTEIN EZH2; METHYLATION; BIOLOGY; SUBGROUPS; SURVIVAL; GENES;

D O I：

10.1038/ng.518

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Follicular lymphoma (FL) and the GCB subtype of diffuse large B-cell lymphoma (DLBCL) derive from germinal center B cells(1). Targeted resequencing studies have revealed mutations in various genes encoding proteins in the NF-kappa B pathway(2,3) that contribute to the activated B-cell (ABC) DLBCL subtype, but thus far few GCB-specific mutations have been identified(4). Here we report recurrent somatic mutations affecting the polycomb-group oncogene(5) EZH2, which encodes a histone methyltransferase responsible for trimethylating Lys27 of histone H3 (H3K27). After the recent discovery of mutations in KDM6A (UTX), which encodes the histone H3K27me3 demethylase UTX, in several cancer types(6), EZH2 is the second histone methyltransferase gene found to be mutated in cancer. These mutations, which result in the replacement of a single tyrosine in the SET domain of the EZH2 protein (Tyr641), occur in 21.7% of GCB DLBCLs and 7.2% of FLs and are absent from ABC DLBCLs. Our data are consistent with the notion that EZH2 proteins with mutant Tyr641 have reduced enzymatic activity in vitro.

引用

页码：181 / U124

页数：7

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