Publication Date:
2010-01-08
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2820242/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2820242/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉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, Arjunan -- 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 -- Futreal, P Andrew -- 077012/Wellcome Trust/United Kingdom -- 077012/Z/05/Z/Wellcome Trust/United Kingdom -- 082359/Wellcome Trust/United Kingdom -- 088340/Wellcome Trust/United Kingdom -- 093867/Wellcome Trust/United Kingdom -- England -- Nature. 2010 Jan 21;463(7279):360-3. doi: 10.1038/nature08672. Epub 2010 Jan 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20054297" target="_blank"〉PubMed〈/a〉
Keywords:
Carcinoma, Renal Cell/*genetics/pathology
;
Cell Hypoxia/genetics
;
Chromatin/metabolism
;
Gene Expression Regulation, Neoplastic
;
*Genes, Neurofibromatosis 2
;
Histone Demethylases
;
Histone-Lysine N-Methyltransferase/*genetics
;
Histones/*metabolism
;
Humans
;
Kidney Neoplasms/*genetics/pathology
;
Mutation/genetics
;
Nuclear Proteins/*genetics
;
Oxidoreductases, N-Demethylating/*genetics
;
Sequence Analysis, DNA
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
