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

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Varela I, Tarpey P, Raine K, Huang D, Ong CK, Stephens P, Davies H, Jones D, Lin ML, Teague J, Bignell G, Butler A, Cho J, Dalgliesh GL, Galappaththige D, Greenman C, Hardy C, Jia M, Latimer C, Lau KW, Marshall J, McLaren S, Menzies A, Mudie L, Stebbings L, Largaespada DA, Wessels LF, Richard S, Kahnoski RJ, Anema J, Tuveson DA, Perez-Mancera PA, Mustonen V, Fischer A, Adams DJ, Rust A, Chan-on W, Subimerb C, Dykema K, Furge K, Campbell PJ, Teh BT, Stratton MR, Futreal PA

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. Epub 2011 Jan 19.

PubMed ID
21248752 [ View in PubMed
]
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 approximately 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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Polypeptides
NameUniProt ID
Cationic amino acid transporter 3Q8WY07Details
Sodium channel protein type 10 subunit alphaQ9Y5Y9Details
Voltage-dependent L-type calcium channel subunit alpha-1CQ13936Details
Histone deacetylase 9Q9UKV0Details
CubilinO60494Details
Low-density lipoprotein receptor-related protein 2P98164Details
Choline transporter-like protein 3Q8N4M1Details
Serine/threonine-protein kinase mTORP42345Details
Activin receptor type-2AP27037Details
Cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha'P51160Details
Fibrillin-2P35556Details
14-3-3 protein beta/alphaP31946Details
Leucine-rich repeat serine/threonine-protein kinase 2Q5S007Details
Cyclin-dependent kinase 17Q00537Details
Hyaluronidase PH-20P38567Details