The spectrum of SWI/SNF mutations, ubiquitous in human cancers.
The spectrum of SWI/SNF mutations, ubiquitous in human cancers.
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DOI：
10.1371/journal.pone.0055119
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Pollack JR
中科院分区：
文献类型：
--
作者：
Shain AH;Pollack JR
SWI/SNF是一种多亚基染色质重塑复合物，其利用ATP水解的能量重新定位核小体，从而调节基因表达。越来越多的证据表明SWI/SNF在某些癌症中起肿瘤抑制剂的作用。然而，人类癌症中SWI/SNF突变的谱尚未得到系统研究。在这里，我们挖掘了来自24项已发表研究的全外显子组测序数据，这些研究代表了来自18种肿瘤诊断的669例病例。SWI/SNF突变在多种人类癌症中广泛存在，具有过量的有害突变，并且总体频率接近TP 53突变。突变最常发生在SMARCA 4酶亚基和被认为赋予功能特异性的亚基（ARID 1A、ARID 1B、PBRM 1和ARID 2）中。SWI/SNF突变并不排斥其他突变的癌症基因，包括TP 53和EZH 2（两者先前都与SWI/SNF相关）。我们的研究结果表明SWI/SNF在多种人类癌症中是一种重要但未被充分认识的肿瘤抑制因子，并为指导未来的研究提供了关键资源。
SWI/SNF is a multi-subunit chromatin remodeling complex that uses the energy of ATP hydrolysis to reposition nucleosomes, thereby modulating gene expression. Accumulating evidence suggests that SWI/SNF functions as a tumor suppressor in some cancers. However, the spectrum of SWI/SNF mutations across human cancers has not been systematically investigated. Here, we mined whole-exome sequencing data from 24 published studies representing 669 cases from 18 neoplastic diagnoses. SWI/SNF mutations were widespread across diverse human cancers, with an excess of deleterious mutations, and an overall frequency approaching TP53 mutation. Mutations occurred most commonly in the SMARCA4 enzymatic subunit, and in subunits thought to confer functional specificity (ARID1A, ARID1B, PBRM1, and ARID2). SWI/SNF mutations were not mutually-exclusive of other mutated cancer genes, including TP53 and EZH2 (both previously linked to SWI/SNF). Our findings implicate SWI/SNF as an important but under-recognized tumor suppressor in diverse human cancers, and provide a key resource to guide future investigations.
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影响因子：
3.7
作者：
DelBove, Jessica;Rosson, Gary;Weissman, Bernard E.
通讯作者：
Weissman, Bernard E.
影响因子：
3.9
作者：
Medina, Pedro P.;Romero, Octavio A.;Sanchez-Cespedes, Montse
通讯作者：
Sanchez-Cespedes, Montse
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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
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Papadopoulos N
DOI：
10.1126/science.1164382
发表时间：
2008-09-26
期刊：
Science (New York, N.Y.)
影响因子：
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作者：
Parsons DW;Jones S;Zhang X;Lin JC;Leary RJ;Angenendt P;Mankoo P;Carter H;Siu IM;Gallia GL;Olivi A;McLendon R;Rasheed BA;Keir S;Nikolskaya T;Nikolsky Y;Busam DA;Tekleab H;Diaz LA Jr;Hartigan J;Smith DR;Strausberg RL;Marie SK;Shinjo SM;Yan H;Riggins GJ;Bigner DD;Karchin R;Papadopoulos N;Parmigiani G;Vogelstein B;Velculescu VE;Kinzler KW
通讯作者：
Kinzler KW
DOI：
10.1126/science.1198056
发表时间：
2011-01-28
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Parsons DW;Li M;Zhang X;Jones S;Leary RJ;Lin JC;Boca SM;Carter H;Samayoa J;Bettegowda C;Gallia GL;Jallo GI;Binder ZA;Nikolsky Y;Hartigan J;Smith DR;Gerhard DS;Fults DW;VandenBerg S;Berger MS;Marie SK;Shinjo SM;Clara C;Phillips PC;Minturn JE;Biegel JA;Judkins AR;Resnick AC;Storm PB;Curran T;He Y;Rasheed BA;Friedman HS;Keir ST;McLendon R;Northcott PA;Taylor MD;Burger PC;Riggins GJ;Karchin R;Parmigiani G;Bigner DD;Yan H;Papadopoulos N;Vogelstein B;Kinzler KW;Velculescu VE
通讯作者：
Velculescu VE