Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma.
Article Details
- CitationCopy to clipboard
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.
DrugBank Data that Cites this Article
- Polypeptides
Name UniProt ID Cationic amino acid transporter 3 Q8WY07 Details Sodium channel protein type 10 subunit alpha Q9Y5Y9 Details Voltage-dependent L-type calcium channel subunit alpha-1C Q13936 Details Histone deacetylase 9 Q9UKV0 Details Cubilin O60494 Details Low-density lipoprotein receptor-related protein 2 P98164 Details Choline transporter-like protein 3 Q8N4M1 Details Serine/threonine-protein kinase mTOR P42345 Details Activin receptor type-2A P27037 Details Cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha' P51160 Details Fibrillin-2 P35556 Details 14-3-3 protein beta/alpha P31946 Details Leucine-rich repeat serine/threonine-protein kinase 2 Q5S007 Details Cyclin-dependent kinase 17 Q00537 Details Hyaluronidase PH-20 P38567 Details