Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes.

Dalgliesh, GL, Furge, K, Greenman, C, Chen, L, Bignell, G, Butler, A, Davies, H, Edkins, S, Hardy, C, Latimer, C, Teague, J, Andrews, J, Barthorpe, S, Beare, D, Buck, G, Campbell, PJ, Forbes, S, Jia, M, Jones, D, Knott, H, Kok, CY, Lau, KW, Leroy, C, Lin, M-L, McBride, DJ, Maddison, M, Maguire, S, McLay, K, Menzies, A, Mironenko, T, Mulderrig, L, Mudie, L, O'Meara, S, Pleasance, E, Rajasingham, A, Shepherd, R, Smith, R, Stebbings, L, Stephens, P, Tang, G, Tarpey, PS, Turrell, K, Dykema, KJ, Khoo, SK, Petillo, D, Wondergem, B, Anema, J, Kahnoski, RJ, Teh, BT, Stratton, MR and Futreal, PA (2010) Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes. Nature, 463 (7279). pp. 360-363. ISSN 1476-4687

Full text not available from this repository. (Request a copy)

Abstract

Clear cell renal cell carcinoma (ccRCC) is the most common form of adult kidney cancer, characterized by the presence of inactivating mutations in the VHL gene in most cases, and by infrequent somatic mutations in known cancer genes. To determine further the genetics of ccRCC, we have sequenced 101 cases through 3,544 protein-coding genes. Here we report the identification of inactivating mutations in two genes encoding enzymes involved in histone modification-SETD2, a histone H3 lysine 36 methyltransferase, and JARID1C (also known as KDM5C), a histone H3 lysine 4 demethylase-as well as mutations in the histone H3 lysine 27 demethylase, UTX (KMD6A), that we recently reported. The results highlight the role of mutations in components of the chromatin modification machinery in human cancer. Furthermore, NF2 mutations were found in non-VHL mutated ccRCC, and several other probable cancer genes were identified. These results indicate that substantial genetic heterogeneity exists in a cancer type dominated by mutations in a single gene, and that systematic screens will be key to fully determining the somatic genetic architecture of cancer.

Item Type: Article
Faculty \ School: Faculty of Science > School of Computing Sciences
Related URLs:
Depositing User: Christopher Greenman
Date Deposited: 22 Jun 2011 12:00
Last Modified: 03 Jan 2019 10:30
URI: https://ueaeprints.uea.ac.uk/id/eprint/30587
DOI: 10.1038/nature08672

Actions (login required)

View Item