2. Academic Validation
  3. 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

  • Nature. 2011 Jan 27;469(7331):539-42. doi: 10.1038/nature09639.
Ignacio Varela 1,  Patrick Tarpey,  Keiran Raine,  Dachuan Huang,  Choon Kiat Ong,  Philip Stephens,  Helen Davies,  David Jones,  Meng-Lay Lin,  Jon Teague,  Graham Bignell,  Adam Butler,  Juok Cho,  Gillian L Dalgliesh,  Danushka Galappaththige,  Chris Greenman,  Claire Hardy,  Mingming Jia,  Calli Latimer,  King Wai Lau,  John Marshall,  Stuart McLaren,  Andrew Menzies,  Laura Mudie,  Lucy Stebbings,  David A Largaespada,  L F A Wessels,  Stephane Richard,  Richard J Kahnoski,  John Anema,  David A Tuveson,  Pedro A Perez-Mancera,  Ville Mustonen,  Andrej Fischer,  David J Adams,  Alistair Rust,  Waraporn Chan-on,  Chutima Subimerb,  Karl Dykema,  Kyle Furge,  Peter J Campbell,  Bin Tean Teh,  Michael R Stratton,  P Andrew Futreal
Affiliations

Affiliation

  • 1 Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK.
PMID: 21248752 DOI: 10.1038/nature09639
Abstract

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.

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