Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes

Dalgliesh, Gillian L., Furge, Kyle, Greenman, Chris, Chen, Lina, Bignell, Graham, Butler, Adam, Davies, Helen, Edkins, Sarah, Hardy, Claire, Latimer, Calli, Teague, Jon, Andrews, Jenny, Barthorpe, Syd, Beare, Dave, Buck, Gemma, Campbell, Peter J., Forbes, Simon, Jia, Mingming, Jones, David, Knott, Henry, Kok, Chai Yin, Lau, King Wai, Leroy, Catherine, Lin, Meng-Lay, McBride, David J., Maddison, Mark, Maguire, Simon, McLay, Kirsten, Menzies, Andrew, Mironenko, Tatiana, Mulderrig, Lee, Mudie, Laura, O'Meara, Sarah, Pleasance, Erin, Rajasingham, Aarjunan, Shepherd, Rebecca, Smith, Raffaella, Stebbings, Lucy, Stephens, Philip, Tang, Gurpreet, Tarpey, Patrick S., Turrell, Kelly, Dykema, Karl J., Khoo, Sok Kean, Petillo, David, Wondergem, Bill, Anema, John, Kahnoski, Richard J., Teh, Bin Tean, Stratton, Michael R. and Futreal, P. Andrew (2010) Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes. Nature, 463 (7279). pp. 360-363. ISSN 1476-4687

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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
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 Computing Sciences
UEA Research Groups:	Faculty of Science > Research Groups > Computational Biology
Depositing User:	Christopher Greenman
Date Deposited:	22 Jun 2011 11:00
Last Modified:	21 Apr 2023 07:32
URI:	https://ueaeprints.uea.ac.uk/id/eprint/30587
DOI:	10.1038/nature08672

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