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

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, 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 and Greenman, Christopher (2011) Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma. Nature, 469 (7331). pp. 539-542. ISSN 1476-4687

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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 ~3,500 genes by PCR-based exon re-sequencing identified several new cancer genes in ccRCC including UTX (also known as KDM6A), 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. 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.

Item Type: Article
Uncontrolled Keywords: sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School: Faculty of Science > School of Biological Sciences
Faculty of Science > School of Computing Sciences

UEA Research Groups: Faculty of Science > Research Groups > Computational Biology
Depositing User: Christopher Greenman
Date Deposited: 22 Jun 2011 10:57
Last Modified: 21 Apr 2023 23:54
URI: https://ueaeprints.uea.ac.uk/id/eprint/30581
DOI: 10.1038/nature09639

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