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Pubmed ID :20054297
Publication Date : //

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


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.

Authors : 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 ,

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