Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes.
Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes.
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作者：
透明细胞肾细胞癌（ccRCC）是成人肾癌的最常见形式，其特征在于在大多数情况下存在VHL基因中的失活突变，并且在已知癌症基因中存在罕见的体细胞突变。为了进一步阐明ccRCC的遗传学，我们通过3544个蛋白编码基因对101例病例进行了测序。在这里，我们报告的失活突变的两个基因编码的酶参与组蛋白修饰，SETD2，组蛋白H3赖氨酸36甲基转移酶和JARID1C（KDM5C），组蛋白H3赖氨酸4脱甲基酶除了突变的组蛋白H3赖氨酸27脱甲基酶，UTX（KMD6A），我们最近报道。这些结果突出了突变在人类癌症中染色质修饰机制的组成部分中的作用。此外，在非VHL突变的ccRCC中发现了NF 2突变，并鉴定了几种其他可能的癌症基因。这些结果表明，大量的遗传异质性存在于由单个基因突变主导的癌症类型中，并且系统筛选将是充分阐明癌症的体细胞遗传结构的关键。
Clear cell renal cell carcinoma (ccRCC) is the most common form of adult kidney cancer, characterised by the presence of inactivating mutations in the VHL gene in the majority of cases and by infrequent somatic mutations in known cancer genes. To elucidate further the genetics of ccRCC, we have sequenced 101 cases through 3544 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 (KDM5C), a histone H3 lysine 4 demethylase in addition to mutations in the histone H3 lysine 27 demethylase, UTX (KMD6A), we recently reported. The results highlight the role of mutations in components of the chromatin modification machinery in human cancer. Additionally, NF2 mutations were found in non-VHL mutated ccRCC and several other likely 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 elucidating the somatic genetic architecture of cancer.
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DOI：
10.1073/pnas.0505337102
发表时间：
2005-08-09
影响因子：
11.1
作者：
Huh, KW;DeMasi, J;Münger, K
通讯作者：
Münger, K
DOI：
10.1126/science.1164382
发表时间：
2008-09-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Parsons DW;Jones S;Zhang X;Lin JC;Leary RJ;Angenendt P;Mankoo P;Carter H;Siu IM;Gallia GL;Olivi A;McLendon R;Rasheed BA;Keir S;Nikolskaya T;Nikolsky Y;Busam DA;Tekleab H;Diaz LA Jr;Hartigan J;Smith DR;Strausberg RL;Marie SK;Shinjo SM;Yan H;Riggins GJ;Bigner DD;Karchin R;Papadopoulos N;Parmigiani G;Vogelstein B;Velculescu VE;Kinzler KW
通讯作者：
Kinzler KW
影响因子：
11.2
作者：
Banks, RE;Tirukonda, P;Selby, PJ
通讯作者：
Selby, PJ
影响因子：
56.9
作者：
Lee, Min Gyu;Villa, Raffaella;Shiekhattar, Ramin
通讯作者：
Shiekhattar, Ramin
影响因子：
50.3
作者：
Mandriota, SJ;Turner, KJ;Maxwell, PH
通讯作者：
Maxwell, PH