Exome sequencing identifies GRIN2A as frequently mutated in melanoma

被引：362

作者：

Wei, Xiaomu ^{[1
]}

Walia, Vijay ^{[1
]}

Lin, Jimmy C. ^{[2
,3
]}

Teer, Jamie K. ^{[4
]}

Prickett, Todd D. ^{[1
]}

Gartner, Jared ^{[1
]}

Davis, Sean ^{[5
]}

Stemke-Hale, Katherine ^{[7
]}

Davies, Michael A. ^{[7
,8
]}

Gershenwald, Jeffrey E. ^{[9
,10
]}

Robinson, William ^{[11
]}

Robinson, Steven ^{[11
]}

Rosenberg, Steven A. ^{[12
]}

Samuels, Yardena ^{[1
]}

机构：

[1] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA

[2] Ludwig Ctr Canc Genet & Therapeut, Baltimore, MD USA

[3] Johns Hopkins Kimmel Canc Ctr, Howard Hughes Med Inst, Baltimore, MD USA

[4] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA

[5] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA

[6] NHGRI, NIH Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA

[7] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA

[8] Univ Texas MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Houston, TX 77030 USA

[9] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA

[10] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA

[11] Univ Colorado, Denver Sch Med, Div Med Oncol, Aurora, CO USA

[12] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA

来源：

NATURE GENETICS | 2011年 / 43卷 / 05期

基金：

美国国家卫生研究院;

关键词：

MUTATIONS; GENE; EXPRESSION; RECEPTORS; REVEALS; TRRAP;

D O I：

10.1038/ng.810

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

The incidence of melanoma is increasing more than any other cancer, and knowledge of its genetic alterations is limited. To systematically analyze such alterations, we performed whole-exome sequencing of 14 matched normal and metastatic tumor DNAs. Using stringent criteria, we identified 68 genes that appeared to be somatically mutated at elevated frequency, many of which are not known to be genetically altered in tumors. Most importantly, we discovered that TRRAP harbored a recurrent mutation that clustered in one position (p. Ser722Phe) in 6 out of 167 affected individuals (similar to 4%), as well as a previously unidentified gene, GRIN2A, which was mutated in 33% of melanoma samples. The nature, pattern and functional evaluation of the TRRAP recurrent mutation suggest that TRRAP functions as an oncogene. Our study provides, to our knowledge, the most comprehensive map of genetic alterations in melanoma to date and suggests that the glutamate signaling pathway is involved in this disease.

引用

页码：442 / +

页数：7

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