Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin.
Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin.
复制标题
体细胞突变改变生发中心起源的滤泡性和弥漫性大 B 细胞淋巴瘤中的 EZH2 (Tyr641)。
DOI：
10.1038/ng.518
复制
发表时间：
2010-02
期刊：
影响因子：
30.8
通讯作者：
Marra, Marco A.
中科院分区：
文献类型：
--
作者：
Morin, Ryan D.;Johnson, Nathalie A.;Severson, Tesa M.;Mungall, Andrew J.;An, Jianghong;Goya, Rodrigo;Paul, Jessica E.;Boyle, Merrill;Woolcock, Bruce W.;Kuchenbauer, Florian;Yap, Damian;Humphries, R. Keith;Griffith, Obi L.;Shah, Sohrab;Zhu, Henry;Kimbara, Michelle;Shashkin, Pavel;Charlot, Jean F.;Tcherpakov, Marianna;Corbett, Richard;Tam, Angela;Varhol, Richard;Smailus, Duane;Moksa, Michelle;Zhao, Yongjun;Delaney, Allen;Qian, Hong;Birol, Inanc;Schein, Jacqueline;Moore, Richard;Holt, Robert;Horsman, Doug E.;Connors, Joseph M.;Jones, Steven;Aparicio, Samuel;Hirst, Martin;Gascoyne, Randy D.;Marra, Marco A.
滤泡性淋巴瘤（FL）和弥漫性大B细胞淋巴瘤（DLBCL）的GCB亚型来源于生殖中心B细胞。靶向重测序研究揭示了NF-κB途径中编码蛋白质的各种基因的突变，这些突变导致了激活的B细胞（ABC）DLBCL亚型，但迄今为止几乎没有发现GCB特异性突变。在这里，我们报告了影响多梳组癌基因EZH 2的复发性体细胞突变，EZH 2编码一种负责组蛋白H3（H3 K27）的三甲基化Lys 27的组蛋白甲基转移酶。在最近发现编码组蛋白H3 K27 me 3去甲基化酶UTX的KDM 6A（UTX）在几种癌症类型中发生突变后，EZH 2是第二个在癌症中发现突变的组蛋白甲基转移酶基因。这些突变导致EZH 2蛋白的SET结构域中的单个酪氨酸（Tyr 641）的替换，发生在21.7%的GCB DLBCL和7.2%的FL中，并且在ABC DLBCL中不存在。我们的数据与具有突变Tyr 641的EZH 2蛋白在体外具有降低的酶活性的概念一致。
Follicular lymphoma (FL) and the GCB subtype of diffuse large B-cell lymphoma (DLBCL) derive from germinal center B cells. Targeted resequencing studies have revealed mutations in various genes encoding proteins in the NF-κB pathway,that contribute to the activated B-cell (ABC) DLBCL subtype, but thus far few GCB-specific mutations have been identified. Here we report recurrent somatic mutations affecting the polycomb-group oncogeneEZH2, which encodes a histone methyltransferase responsible for trimethylating Lys27 of histone H3 (H3K27). After the recent discovery of mutations inKDM6A(UTX), which encodes the histone H3K27me3 demethylase UTX, in several cancer types,EZH2is 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 activityin vitro.
登录
查看更多内容
影响因子：
20.3
作者：
Hans, CP;Weisenburger, DD;Armitage, JO
通讯作者：
Armitage, JO
影响因子：
14.9
作者：
Kopp, J;Schwede, T
通讯作者：
Schwede, T
影响因子：
3.7
作者：
Baskind HA;Na L;Ma Q;Patel MP;Geenen DL;Wang QT
通讯作者：
Wang QT
影响因子：
64.8
作者：
Alizadeh, AA;Eisen, MB;Staudt, LM
通讯作者：
Staudt, LM
影响因子：
64.8
作者：
Compagno, Mara;Lim, Wei Keat;Grunn, Adina;Nandula, Subhadra V.;Brahmachary, Manisha;Shen, Qiong;Bertoni, Francesco;Ponzoni, Maurilio;Scandurra, Marta;Califano, Andrea;Bhagat, Govind;Chadburn, Amy;Dalla-Favera, Riccardo;Pasqualucci, Laura
通讯作者：
Pasqualucci, Laura