Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma
quwubin 添加于 2011-3-24 08:53
| 1722 次阅读 | 0 个评论
作 者
Ignacio Varela1, Patrick Tarpey1, Keiran Raine1, Dachuan Huang2, Choon Kiat Ong2, Philip Stephens1, Helen Davies1, David Jones1, , Meng-Lay Lin1, Jon Teague1, Graham Bignell1, Adam Butler1, Juok Cho1, Gillian L. Dalgliesh1, Danushka Galappaththige1, , Chris Greenman1, Claire Hardy1, Mingming Jia1, Calli Latimer1, KingWai Lau1, John Marshall1, Stuart McLaren1, Andrew Menzies1, , Laura Mudie1, Lucy Stebbings1, David A. Largaespada3, L. F. A.Wessels4, Stephane Richard5, 6, Richard J.Kahnoski7, John Anema7, , David A.Tu ... 摘 要
The genetics of renal cancer is dominated by inactivation of theVHL
tumour suppressor gene in clear cell carcinoma (ccRCC), the commonest
histological subtype. A recent large-scale screen of 3,500
genes byPCR-based exonre-sequencingidentified severalnewcancer
genes in ccRCC includingUTX (also known asKDM6A)1, JARID1C
(also known as KDM5C) and SETD2 (ref. 2). 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 histoneH3regulates chromatin structure
and is implicated in transcriptional control3. 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
remodelling complex gene PBRM1 (ref. 4) 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.-
详细资料
- 文献种类:期刊
- 期刊名称: Nature
- 期刊缩写: Nature
- 期卷页: 2011年 第469卷 第7331期 539-542页
- ISBN: 0028-0836
评论( 人)
相关链接
DOI URL
浙公网安备 33010202000686号 ( 浙ICP备09035230号-1 )
