Histone Methyltransferase Gene SETD2 Is a Novel Tumor Suppressor Gene in Clear Cell Renal Cell Carcinoma

被引：195

作者：

Duns, Gerben ^{[1
]}

van den Berg, Eva ^{[1
]}

van Duivenbode, Inge ^{[1
]}

Osinga, Jan ^{[1
]}

Hollema, Harry ^{[2
]}

Hofstra, Robert M. W. ^{[1
]}

Kok, Klaas ^{[1
]}

机构：

[1] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9700 RB Groningen, Netherlands

[2] Univ Groningen, Univ Med Ctr Groningen, Dept Pathol, NL-9700 RB Groningen, Netherlands

来源：

CANCER RESEARCH | 2010年 / 70卷 / 11期

关键词：

ILLUMINA MICROARRAY; CANCER; IDENTIFICATION; MUTATIONS; INACTIVATION; METHYLATION; SEQUENCE;

D O I：

10.1158/0008-5472.CAN-10-0120

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Sporadic clear cell renal cell carcinoma (cRCC) is genetically characterized by the recurrent loss of the short arm of chromosome 3, with a hotspot for copy number loss in the 3p21 region. We applied a method called "gene identification by nonsense-mediated mRNA decay inhibition" to a panel of 10 cRCC cell lines with 3p21 copy number loss to identify biallelic inactivated genes located at 3p21. This revealed inactivation of the histone methyltransferase gene SETD2, located on 3p21.31, as a common event in cRCC cells. SETD2 is nonredundantly responsible for trimethylation of the histone mark H3K36. Consistent with this function, we observed loss or a decrease of H3K36me3 in 7 out of the 10 cRCC cell lines. Identification of missense mutations in 2 out of 10 primary cRCC tumor samples added support to the involvement of loss of SETD2 function in the development of cRCC tumors. Cancer Res; 70(11); 4287-91. (C) 2010 AACR.

引用

页码：4287 / 4291

页数：5

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