Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma

被引：990

作者：

Varela, Ignacio ^{[2
]}

Tarpey, Patrick ^{[2
]}

Raine, Keiran ^{[2
]}

Huang, Dachuan ^{[1
]}

Ong, Choon Kiat ^{[1
]}

Stephens, Philip ^{[2
]}

Davies, Helen ^{[2
]}

Jones, David ^{[2
]}

Lin, Meng-Lay ^{[2
]}

Teague, Jon ^{[2
]}

Bignell, Graham ^{[2
]}

Butler, Adam ^{[2
]}

Cho, Juok ^{[2
]}

Dalgliesh, Gillian L. ^{[2
]}

Galappaththige, Danushka ^{[2
]}

Greenman, Chris ^{[2
]}

Hardy, Claire ^{[2
]}

Jia, Mingming ^{[2
]}

Latimer, Calli ^{[2
]}

Lau, King Wai ^{[2
]}

Marshall, John ^{[2
]}

McLaren, Stuart ^{[2
]}

Menzies, Andrew ^{[2
]}

Mudie, Laura ^{[2
]}

Stebbings, Lucy ^{[2
]}

Largaespada, David A. ^{[3
]}

Wessels, L. F. A. ^{[4
]}

Richard, Stephane ^{[5
,6
,7
]}

Kahnoski, Richard J. ^{[8
]}

Anema, John ^{[8
]}

Tuveson, David A. ^{[9
]}

Perez-Mancera, Pedro A. ^{[9
]}

Mustonen, Ville ^{[10
]}

Fischer, Andrej ^{[10
,11
]}

Adams, David J. ^{[10
]}

Rust, Alistair ^{[10
]}

Chan-on, Waraporn ^{[1
]}

Subimerb, Chutima ^{[1
]}

Dykema, Karl ^{[12
]}

Furge, Kyle ^{[12
]}

Campbell, Peter J. ^{[2
]}

Teh, Bin Tean ^{[1
,13
,14
]}

Stratton, Michael R. ^{[2
,15
]}

Futreal, P. Andrew ^{[2
]}

机构：

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

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

[3] Univ Minnesota, Mason Canc Ctr, Minneapolis, MN 55455 USA

[4] Netherlands Canc Inst, Dept Mol Biol, NL-1066 CX Amsterdam, Netherlands

[5] Fac Med Paris Sud, INSERM, U753, Genet Oncol EPHE, F-94805 Villejuif, France

[6] Inst Cancerol Gustave Roussy, F-94805 Villejuif, France

[7] Hop Bicetre, AP HP, Serv Urol, Ctr Expert Natl Canc Rares INCa PREDIR, F-94276 Le Kremlin Bicetre, France

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

[9] Canc Res UK, Cambridge Res Inst, Li Ka Shing Ctr, Cambridge CB2 0RE, England

[10] Wellcome Trust Sanger Inst, Hinxton CB10 1SA, England

[11] Univ Cologne, Inst Theoret Phys, D-50937 Cologne, Germany

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

[13] DUKE NUS Grad Med Sch, Lab Canc Therapeut, Singapore, Singapore

[14] Van Andel Res Inst, Canc Genet Lab, Grand Rapids, MI 49503 USA

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

来源：

NATURE | 2011年 / 469卷 / 7331期

基金：

英国惠康基金;

关键词：

TUMOR-SUPPRESSOR GENE; CELL CARCINOMA; CANCER; MUTAGENESIS; BAF180; ARID1A; MOUSE; INACTIVATION; SENESCENCE; INDUCTION;

D O I：

10.1038/nature09639

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：

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 similar to 3,500 genes by PCR-based exon re-sequencing identified several new cancer genes in ccRCC including UTX (also known as KDM6A)(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 histone H3 regulates chromatin structure and is implicated in transcriptional control(3). 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.

引用

页码：539 / 542

页数：4

共 31 条

[1] Polybromo-associated BRG1-associated factor components BRD7 and BAF180 are critical regulators of p53 required for induction of replicative senescence [J].

Burrows, Anna E. ;

Smogorzewska, Agata ;

Elledge, Stephen J. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (32) :14280-14285

[2] Polybromo-1-bromodomains bind histone H3 at specific acetyl-lysine positions [J].

Chandrasekaran, Renu ;

Thompson, Martin .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2007, 355 (03) :661-666

[3]

Clifford SC, 1998, GENE CHROMOSOME CANC, V22, P200, DOI 10.1002/(SICI)1098-2264(199807)22:3<200::AID-GCC5>3.0.CO

[4]

2-#

[5] Cancer gene discovery in solid tumours using transposon-based somatic mutagenesis in the mouse [J].

Collier, LS ;

Carlson, CM ;

Ravimohan, S ;

Dupuy, AJ ;

Largaespada, DA .

NATURE, 2005, 436 (7048) :272-276

[6] Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes [J].

Dalgliesh, Gillian L. ;

Furge, Kyle ;

Greenman, Chris ;

Chen, Lina ;

Bignell, Graham ;

Butler, Adam ;

Davies, Helen ;

Edkins, Sarah ;

Hardy, Claire ;

Latimer, Calli ;

Teague, Jon ;

Andrews, Jenny ;

Barthorpe, Syd ;

Beare, Dave ;

Buck, Gemma ;

Campbell, Peter J. ;

Forbes, Simon ;

Jia, Mingming ;

Jones, David ;

Knott, Henry ;

Kok, Chai Yin ;

Lau, King Wai ;

Leroy, Catherine ;

Lin, Meng-Lay ;

McBride, David J. ;

Maddison, Mark ;

Maguire, Simon ;

McLay, Kirsten ;

Menzies, Andrew ;

Mironenko, Tatiana ;

Mulderrig, Lee ;

Mudie, Laura ;

O'Meara, Sarah ;

Pleasance, Erin ;

Rajasingham, Arjunan ;

Shepherd, Rebecca ;

Smith, Raffaella ;

Stebbings, Lucy ;

Stephens, Philip ;

Tang, Gurpreet ;

Tarpey, Patrick S. ;

Turrell, Kelly ;

Dykema, Karl J. ;

Khoo, Sok Kean ;

Petillo, David ;

Wondergem, Bill ;

Anema, John ;

Kahnoski, Richard J. ;

Teh, Bin Tean ;

Stratton, Michael R. .

NATURE, 2010, 463 (7279) :360-363

[7] Solution hybrid selection with ultra-long oligonucleotides for massively parallel targeted sequencing [J].

Gnirke, Andreas ;

Melnikov, Alexandre ;

Maguire, Jared ;

Rogov, Peter ;

LeProust, Emily M. ;

Brockman, William ;

Fennell, Timothy ;

Giannoukos, Georgia ;

Fisher, Sheila ;

Russ, Carsten ;

Gabriel, Stacey ;

Jaffe, David B. ;

Lander, Eric S. ;

Nusbaum, Chad .

NATURE BIOTECHNOLOGY, 2009, 27 (02) :182-189

[8] Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse [J].

Hingorani, SR ;

Petricoin, EF ;

Maitra, A ;

Rajapakse, V ;

King, C ;

Jacobetz, MA ;

Ross, S ;

Conrads, TP ;

Veenstra, TD ;

Hitt, BA ;

Kawaguchi, Y ;

Johann, D ;

Liotta, LA ;

Crawford, HC ;

Putt, ME ;

Jacks, T ;

Wright, CVE ;

Hruban, RH ;

Lowy, AM ;

Tuveson, DA .

CANCER CELL, 2003, 4 (06) :437-450

[9] Core signaling pathways in human pancreatic cancers revealed by global genomic analyses [J].

Jones, Sian ;

Zhang, Xiaosong ;

Parsons, D. Williams ;

Lin, Jimmy Cheng-Ho ;

Leary, Rebecca J. ;

Angenendt, Philipp ;

Mankoo, Parminder ;

Carter, Hannah ;

Kamiyama, Hirohiko ;

Jimeno, Antonio ;

Hong, Seung-Mo ;

Fu, Baojin ;

Lin, Ming-Tseh ;

Calhoun, Eric S. ;

Kamiyama, Mihoko ;

Walter, Kimberly ;

Nikolskaya, Tatiana ;

Nikolsky, Yuri ;

Hartigan, James ;

Smith, Douglas R. ;

Hidalgo, Manuel ;

Leach, Steven D. ;

Klein, Alison P. ;

Jaffee, Elizabeth M. ;

Goggins, Michael ;

Maitra, Anirban ;

Iacobuzio-Donahue, Christine ;

Eshleman, James R. ;

Kern, Scott E. ;

Hruban, Ralph H. ;

Karchin, Rachel ;

Papadopoulos, Nickolas ;

Parmigiani, Giovanni ;

Vogelstein, Bert ;

Velculescu, Victor E. ;

Kinzler, Kenneth W. .

SCIENCE, 2008, 321 (5897) :1801-1806

[10] Frequent Mutations of Chromatin Remodeling Gene ARID1A in Ovarian Clear Cell Carcinoma [J].

Jones, Sian ;

Wang, Tian-Li ;

Shih, Ie-Ming ;

Mao, Tsui-Lien ;

Nakayama, Kentaro ;

Roden, Richard ;

Glas, Ruth ;

Slamon, Dennis ;

Diaz, Luis A., Jr. ;

Vogelstein, Bert ;

Kinzler, Kenneth W. ;

Velculescu, Victor E. ;

Papadopoulos, Nickolas .

SCIENCE, 2010, 330 (6001) :228-231

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