Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes

被引：912

作者：

Dalgliesh, Gillian L. ^{[6
]}

Furge, Kyle ^{[5
]}

Greenman, Chris ^{[6
]}

Chen, Lina ^{[6
]}

Bignell, Graham ^{[6
]}

Butler, Adam ^{[6
]}

Davies, Helen ^{[6
]}

Edkins, Sarah ^{[6
]}

Hardy, Claire ^{[6
]}

Latimer, Calli ^{[6
]}

Teague, Jon ^{[6
]}

Andrews, Jenny ^{[6
]}

Barthorpe, Syd ^{[6
]}

Beare, Dave ^{[6
]}

Buck, Gemma ^{[6
]}

Campbell, Peter J. ^{[6
]}

Forbes, Simon ^{[6
]}

Jia, Mingming ^{[6
]}

Jones, David ^{[6
]}

Knott, Henry ^{[6
]}

Kok, Chai Yin ^{[6
]}

Lau, King Wai ^{[6
]}

Leroy, Catherine ^{[6
]}

Lin, Meng-Lay ^{[6
]}

McBride, David J. ^{[6
]}

Maddison, Mark ^{[6
]}

Maguire, Simon ^{[6
]}

McLay, Kirsten ^{[6
]}

Menzies, Andrew ^{[6
]}

Mironenko, Tatiana ^{[6
]}

Mulderrig, Lee ^{[6
]}

Mudie, Laura ^{[6
]}

O'Meara, Sarah ^{[6
]}

Pleasance, Erin ^{[6
]}

Rajasingham, Arjunan ^{[6
]}

Shepherd, Rebecca ^{[6
]}

Smith, Raffaella ^{[6
]}

Stebbings, Lucy ^{[6
]}

Stephens, Philip ^{[6
]}

Tang, Gurpreet ^{[6
]}

Tarpey, Patrick S. ^{[6
]}

Turrell, Kelly ^{[6
]}

Dykema, Karl J. ^{[5
]}

Khoo, Sok Kean ^{[1
]}

Petillo, David ^{[1
]}

Wondergem, Bill ^{[5
]}

Anema, John ^{[2
]}

Kahnoski, Richard J. ^{[2
]}

Teh, Bin Tean ^{[1
,3
]}

Stratton, Michael R. ^{[4
,6
]}

机构：

[1] Van Andel Res Inst, Lab Canc Genert, Grand Rapids, MI 49503 USA

[2] Spectrum Hlth Hosp, Dept Urol, Grand Rapids, MI 49503 USA

[3] Natl Canc Ctr, NCCS VARI Translat Canc Res Lab, Singapore 169610, Singapore

[4] Inst Canc Res, Sutton SM2 5NG, Surrey, England

[5] Van Andel Res Inst, Lab Computat Biol, Grand Rapids, MI 49503 USA

[6] Wellcome Trust Sanger Inst, Canc Genome Project, Hinxton CB10 1SA, England

来源：

NATURE | 2010年 / 463卷 / 7279期

基金：

英国惠康基金;

关键词：

CELL CARCINOMA; PROGNOSTIC-SIGNIFICANCE; SOMATIC MUTATIONS; CANCER GENOMES; P600;

D O I：

10.1038/nature08672

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Clear cell renal cell carcinoma (ccRCC) is the most common form of adult kidney cancer, characterized by the presence of inactivating mutations in the VHL gene in most cases(1,2), and by infrequent somatic mutations in known cancer genes. To determine further the genetics of ccRCC, we have sequenced 101 cases through 3,544 protein-coding genes. Here we report the identification of inactivating mutations in two genes encoding enzymes involved in histone modification-SETD2, a histone H3 lysine 36 methyltransferase, and JARID1C (also known as KDM5C), a histone H3 lysine 4 demethylase-as well as mutations in the histone H3 lysine 27 demethylase, UTX (KMD6A), that we recently reported(3). The results highlight the role of mutations in components of the chromatin modification machinery in human cancer. Furthermore, NF2 mutations were found in non-VHL mutated ccRCC, and several other probable cancer genes were identified. These results indicate that substantial genetic heterogeneity exists in a cancer type dominated by mutations in a single gene, and that systematic screens will be key to fully determining the somatic genetic architecture of cancer.

引用

页码：360 / 363

页数：4

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