Whole exome sequencing identifies novel recurrently mutated genes in patients with splenic marginal zone lymphoma.
Whole exome sequencing identifies novel recurrently mutated genes in patients with splenic marginal zone lymphoma.
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DOI：
10.1371/journal.pone.0083244
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Strefford JC
中科院分区：
文献类型：
--
作者：
Parry M;Rose-Zerilli MJ;Gibson J;Ennis S;Walewska R;Forster J;Parker H;Davis Z;Gardiner A;Collins A;Oscier DG;Strefford JC
脾边缘区淋巴瘤（SMZL）的发病机制在很大程度上仍不清楚。最近的高通量测序研究已经确定了关键通路中的复发突变，最显着的是 >25% 的患者存在 NOTCH2 突变。这些研究基于小型、异质的发现队列，因此仅捕获了 SMZL 基因组中存在的一小部分病变。为了进一步识别相关生化途径中的新致病性突变，我们对 7 名具有 7q 异常和 IGHV1-2*04 基因使用的 SMZL 患者组成的生物学和临床同质队列应用了全外显子组测序 (WES) 和拷贝数 (CN) 分析。我们鉴定了 173 个体细胞非沉默变异，影响 160 个不同的基因。除了对先前报道的几个基因（NOTCH2、TNFAIP3、MAP3K14、MLL2 和 SPEN）中是否存在突变提供独立验证外，我们的研究还定义了 SMZL 中另外八个经常突变的基因；这些基因是 CREBBP、CBFA2T3、AMOTL1、FAT4、FBXO11、PLA2G4D、TRRAP 和 USH2A。通过整合我们的 WES 和 CN 数据，我们确定了 7q 缺失靶向的三个假定突变候选基因（CUL1、EZH2 和 FLNC），其中 FLNC 位于明确表征的 7q 最小缺失区域内。总而言之，这项工作扩大了该疾病中反复突变的癌症基因的报道目录，从而扩大了我们对 SMZL 发病机制的理解。最终，这项工作将有助于建立分层的护理方法，包括靶向治疗的可能性。
The pathogenesis of splenic marginal zone lymphoma (SMZL) remains largely unknown. Recent high-throughput sequencing studies have identified recurrent mutations in key pathways, most notably NOTCH2 mutations in >25% of patients. These studies are based on small, heterogeneous discovery cohorts, and therefore only captured a fraction of the lesions present in the SMZL genome. To identify further novel pathogenic mutations within related biochemical pathways, we applied whole exome sequencing (WES) and copy number (CN) analysis to a biologically and clinically homogeneous cohort of seven SMZL patients with 7q abnormalities and IGHV1-2*04 gene usage. We identified 173 somatic non-silent variants, affecting 160 distinct genes. In additional to providing independent validation of the presence of mutation in several previously reported genes (NOTCH2, TNFAIP3, MAP3K14, MLL2 and SPEN), our study defined eight additional recurrently mutated genes in SMZL; these genes are CREBBP, CBFA2T3, AMOTL1, FAT4, FBXO11, PLA2G4D, TRRAP and USH2A. By integrating our WES and CN data we identified three mutated putative candidate genes targeted by 7q deletions (CUL1, EZH2 and FLNC), with FLNC positioned within the well-characterized 7q minimally deleted region. Taken together, this work expands the reported directory of recurrently mutated cancer genes in this disease, thereby expanding our understanding of SMZL pathogenesis. Ultimately, this work will help to establish a stratified approach to care including the possibility of targeted therapy.
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影响因子：
50.3
作者：
Gruber TA;Larson Gedman A;Zhang J;Koss CS;Marada S;Ta HQ;Chen SC;Su X;Ogden SK;Dang J;Wu G;Gupta V;Andersson AK;Pounds S;Shi L;Easton J;Barbato MI;Mulder HL;Manne J;Wang J;Rusch M;Ranade S;Ganti R;Parker M;Ma J;Radtke I;Ding L;Cazzaniga G;Biondi A;Kornblau SM;Ravandi F;Kantarjian H;Nimer SD;Döhner K;Döhner H;Ley TJ;Ballerini P;Shurtleff S;Tomizawa D;Adachi S;Hayashi Y;Tawa A;Shih LY;Liang DC;Rubnitz JE;Pui CH;Mardis ER;Wilson RK;Downing JR
通讯作者：
Downing JR
DOI：
10.1093/bioinformatics/btq033
发表时间：
2010-03-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Quinlan AR;Hall IM
通讯作者：
Hall IM
影响因子：
11.4
作者：
Bikos, V.;Darzentas, N.;Stamatopoulos, K.
通讯作者：
Stamatopoulos, K.
影响因子：
3.7
作者：
Watkins AJ;Hamoudi RA;Zeng N;Yan Q;Huang Y;Liu H;Zhang J;Braggio E;Fonseca R;de Leval L;Isaacson PG;Wotherspoon A;McPhail ED;Dogan A;Du MQ
通讯作者：
Du MQ
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)。
影响因子：
30.8
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.
通讯作者：
Marra, Marco A.