Exome sequencing of serous endometrial tumors identifies recurrent somatic mutations in chromatin-remodeling and ubiquitin ligase complex genes.
Exome sequencing of serous endometrial tumors identifies recurrent somatic mutations in chromatin-remodeling and ubiquitin ligase complex genes.
复制标题
DOI：
10.1038/ng.2455
复制
发表时间：
2012-12
期刊：
影响因子：
30.8
通讯作者：
Bell, Daphne W.
中科院分区：
文献类型：
--
作者：
Le Gallo, Matthieu;O'Hara, Andrea J.;Rudd, Meghan L.;Urick, Mary Ellen;Hansen, Nancy F.;O'Neil, Nigel J.;Price, Jessica C.;Zhang, Suiyuan;England, Bryant M.;Godwin, Andrew K.;Sgroi, Dennis C.;Hieter, Philip;Mullikin, James C.;Merino, Maria J.;Bell, Daphne W.
子宫内膜癌是全球女性中第六大最常见的癌症，每年造成约74，000人死亡。浆液性子宫内膜癌是一种临床上具有侵袭性的亚型，其遗传病因学定义不明确。我们使用全外显子组测序（WES）在13个原发性浆液性子宫内膜肿瘤中全面搜索约22，000个蛋白质编码基因内的体细胞突变。随后，我们从另外40个浆液性肿瘤中重新测序了18个基因，这些基因在一个以上的肿瘤中突变，和/或形成了丰富的功能组。我们在CHD 4（17%）、EP 300（8%）、ARID 1A（6%）、TSPYL 2（6%）、FBXW 7（29%）、SPOP（8%）、MAP 3 K4（6%）和ABCC 9（6%）中鉴定出高频率的体细胞突变。总的来说，36.5%的浆液性肿瘤发生了染色质重塑基因突变，35%的浆液性肿瘤发生了泛素连接酶复合物基因突变，这表明这些过程的频繁突变破坏是子宫内膜癌最致命形式之一的分子发病机制。
Endometrial cancer is the 6th most commonly diagnosed cancer among women worldwide, causing ~74,000 deaths annually . Serous endometrial cancers are a clinically aggressive subtype with a poorly defined genetic etiology . We used whole exome sequencing (WES) to comprehensively search for somatic mutations within ~22,000 protein-encoding genes among 13 primary serous endometrial tumors. We subsequently resequenced 18 genes that were mutated in more than one tumor, and/or were genes that formed an enriched functional grouping, from 40 additional serous tumors. We identified high frequencies of somatic mutations in CHD4 (17%), EP300 (8%), ARID1A (6%), TSPYL2 (6%), FBXW7 (29%), SPOP (8%), MAP3K4 (6%) and ABCC9 (6%). Overall, 36.5% of serous tumors had mutated a chromatin-remodeling gene and 35% had mutated a ubiquitin ligase complex gene, implicating the frequent mutational disruption of these processes in the molecular pathogenesis of one of the deadliest forms of endometrial cancer.
登录
查看更多内容
影响因子：
5.6
作者：
HENDRICKSON, M;ROSS, J;KEMPSON, R
通讯作者：
KEMPSON, R
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
64.8
作者：
Garnett, Mathew J.;Edelman, Elena J.;Heidorn, Sonja J.;Greenman, Chris D.;Dastur, Anahita;Lau, King Wai;Greninger, Patricia;Thompson, I. Richard;Luo, Xi;Soares, Jorge;Liu, Qingsong;Iorio, Francesco;Surdez, Didier;Chen, Li;Milano, Randy J.;Bignell, Graham R.;Tam, Ah T.;Davies, Helen;Stevenson, Jesse A.;Barthorpe, Syd;Lutz, Stephen R.;Kogera, Fiona;Lawrence, Karl;McLaren-Douglas, Anne;Mitropoulos, Xeni;Mironenko, Tatiana;Thi, Helen;Richardson, Laura;Zhou, Wenjun;Jewitt, Frances;Zhang, Tinghu;O'Brien, Patrick;Boisvert, Jessica L.;Price, Stacey;Hur, Wooyoung;Yang, Wanjuan;Deng, Xianming;Butler, Adam;Choi, Hwan Geun;Chang, JaeWon;Baselga, Jose;Stamenkovic, Ivan;Engelman, Jeffrey A.;Sharma, Sreenath V.;Delattre, Olivier;Saez-Rodriguez, Julio;Gray, Nathanael S.;Settleman, Jeffrey;Futreal, P. Andrew;Haber, Daniel A.;Stratton, Michael R.;Ramaswamy, Sridhar;McDermott, Ultan;Benes, Cyril H.
通讯作者：
Benes, Cyril H.
胰腺神经内分泌肿瘤中经常改变DAXX/ATRX，MEN1和MTOR途径基因。
DOI：
10.1126/science.1200609
发表时间：
2011-03-04
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Jiao Y;Shi C;Edil BH;de Wilde RF;Klimstra DS;Maitra A;Schulick RD;Tang LH;Wolfgang CL;Choti MA;Velculescu VE;Diaz LA Jr;Vogelstein B;Kinzler KW;Hruban RH;Papadopoulos N
通讯作者：
Papadopoulos N
影响因子：
8.8
作者：
通讯作者：
--