Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma.
Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma.
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DOI：
10.1038/nature09639
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发表时间：
2011-01-27
期刊：
影响因子：
64.8
通讯作者：
Futreal, P. Andrew
中科院分区：
文献类型：
--
作者：
Varela, Ignacio;Tarpey, Patrick;Raine, Keiran;Huang, Dachuan;Ong, Choon Kiat;Stephens, Philip;Davies, Helen;Jones, David;Lin, Meng-Lay;Teague, Jon;Bignell, Graham;Butler, Adam;Cho, Juok;Dalgliesh, Gillian L.;Galappaththige, Danushka;Greenman, Chris;Hardy, Claire;Jia, Mingming;Latimer, Calli;Lau, King Wai;Marshall, John;McLaren, Stuart;Menzies, Andrew;Mudie, Laura;Stebbings, Lucy;Largaespada, David A.;Wessels, L. F. A.;Richard, Stephane;Kahnoski, Richard J.;Anema, John;Tuveson, David A.;Perez-Mancera, Pedro A.;Mustonen, Ville;Fischer, Andrej;Adams, David J.;Rust, Alistair;Chan-on, Waraporn;Subimerb, Chutima;Dykema, Karl;Furge, Kyle;Campbell, Peter J.;Teh, Bin Tean;Stratton, Michael R.;Futreal, P. Andrew
肾癌的遗传学由最常见的组织学亚型透明细胞癌(CcRCC)中VHL肿瘤抑制基因的失活所主导。最近通过对3500个基因的大规模筛选，发现了几个新的癌基因，包括UTX(KDM6A)、JARID1C(KDM5C)和SETD2。这些基因编码的酶使组蛋白H3的关键赖氨酸残基去甲基化(UTX，JARID1C)或甲基化(SETD2)。组蛋白H3的这些赖氨酸残基的甲基化状态的改变调节了染色质的结构，并与转录调控有关。然而，这些突变加在一起在不到15%的ccRCC中存在，这表明存在其他目前尚未确定的癌症基因。在这里，我们已经对一系列原发性肾细胞癌的蛋白质编码外显子组进行了测序，并报告了SWI/SNF染色质重塑复合体基因PBRM1是第二个主要的肾细胞癌基因，在41%(92/227)的病例中发生了截短突变。这些数据进一步阐明了ccRCC的体细胞遗传结构，并强调了异常染色质生物学的显著贡献。
The genetics of renal cancer is dominated by inactivation of the VHL tumour suppressor gene in clear cell carcinoma (ccRCC), the commonest histological subtype. A recent large-scale screen of ~3500 genes by PCR-based exon re-sequencing identified several new cancer genes in ccRCC including UTX (KDM6A), JARID1C (KDM5C) and SETD2. These genes encode enzymes that demethylate (UTX, JARID1C) or methylate (SETD2) key lysine residues of histone H3. Modification of the methylation state of these lysine residues of histone H3 regulates chromatin structure and is implicated in transcriptional control. However, together these mutations are present in fewer than 15% of ccRCC, suggesting the existence of additional, currently unidentified cancer genes. Here, we have sequenced the protein coding exome in a series of primary ccRCC and report the identification of the SWI/SNF chromatin remodeling complex gene PBRM1 as a second major ccRCC cancer gene, with truncating mutations in 41% (92/227) of cases. These data further elucidate the somatic genetic architecture of ccRCC and emphasize the marked contribution of aberrant chromatin biology.
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影响因子：
30.8
作者：
Papaemmanuil E;Hosking FJ;Vijayakrishnan J;Price A;Olver B;Sheridan E;Kinsey SE;Lightfoot T;Roman E;Irving JA;Allan JM;Tomlinson IP;Taylor M;Greaves M;Houlston RS
通讯作者：
Houlston RS
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
30.8
作者：
van Haaften, Gijs;Dalgliesh, Gillian L.;Davies, Helen;Chen, Lina;Bignell, Graham;Greenman, Chris;Edkins, Sarah;Hardy, Claire;O'Meara, Sarah;Teague, Jon;Butler, Adam;Hinton, Jonathan;Latimer, Calli;Andrews, Jenny;Barthorpe, Syd;Beare, Dave;Buck, Gemma;Campbell, Peter J.;Cole, Jennifer;Forbes, Simon;Jia, Mingming;Jones, David;Kok, Chai Yin;Leroy, Catherine;Lin, Meng-Lay;McBride, David J.;Maddison, Mark;Maquire, Simon;Mclay, Kirsten;Menzies, Andrew;Mironenko, Tatiana;Mulderrig, Lee;Mudie, Laura;Pleasance, Erin;Shepherd, Rebecca;Smith, Raffaella;Stebbings, Lucy;Stephens, Philip;Tang, Gurpreet;Tarpey, Patrick S.;Turner, Rachel;Turrell, Kelly;Varian, Jennifer;West, Sofie;Widaa, Sara;Wray, Paul;Collins, V. Peter;Ichimura, Koichi;Law, Simon;Wong, John;Yuen, Siu Tsan;Leung, Suet Yi;Tonon, Giovanni;DePinho, Ronald A.;Tai, Yu-Tzu;Anderson, Kenneth C.;Kahnoski, Richard J.;Massie, Aaron;Khoo, Sok Kean;Teh, Bin Tean;Stratton, Michael R.;Futreal, P. Andrew
通讯作者：
Futreal, P. Andrew
DOI：
10.1073/pnas.240208597
发表时间：
2000-11-21
影响因子：
11.1
作者：
Xue, YT;Canman, JC;Wang, WD
通讯作者：
Wang, WD
影响因子：
46.9
作者：
Keng, Vincent W.;Villanueva, Augusto;Chiang, Derek Y.;Dupuy, Adam J.;Ryan, Barbara J.;Matise, Ilze;Silverstein, Kevin A. T.;Sarver, Aaron;Starr, Timothy K.;Akagi, Keiko;Tessarollo, Lino;Collier, Lara S.;Powers, Scott;Lowe, Scott W.;Jenkins, Nancy A.;Copeland, Neal G.;Llovet, Josep M.;Largaespada, David A.
通讯作者：
Largaespada, David A.