Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi

被引：1173

作者：

Van Raamsdonk, Catherine D.

Bezrookove, Vladimir ^{[1
,2
]}

Green, Gary ^{[1
,2
]}

Bauer, Juergen ^{[1
,2
,4
]}

Gaugler, Lona ^{[1
,2
]}

O'Brien, Joan M. ^{[2
,3
]}

Simpson, Elizabeth M. ^{[5
,6
]}

Barsh, Gregory S. ^{[7
]}

Bastian, Boris C. ^{[1
,2
]}

机构：

[1] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA

[2] Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA

[3] Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA 94143 USA

[4] Univ Tubingen, Dept Dermatol, D-72076 Tubingen, Germany

[5] Univ British Columbia, Ctr Mol Med & Therapeut, Vancouver, BC V6T 1Z3, Canada

[6] Univ British Columbia, Dept Med Genet, Vancouver, BC V6T 1Z3, Canada

[7] Stanford Univ, Dept Genet, Stanford, CA 94305 USA

来源：

NATURE | 2009年 / 457卷 / 7229期

基金：

加拿大健康研究院; 美国国家卫生研究院;

关键词：

KINASE-C; BRAF; MELANOCYTES; PATHWAY; CELLS;

D O I：

10.1038/nature07586

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

BRAF and NRAS are common targets for somatic mutations in benign and malignant neoplasms that arise from melanocytes situated in epithelial structures, and lead to constitutive activation of the mitogen- activated protein ( MAP) kinase pathway(1,2). However, BRAF and NRAS mutations are absent in a number of other melanocytic neoplasms in which the equivalent oncogenic events are currently unknown(3). Here we report frequent somatic mutations in the heterotrimeric G protein alpha-subunit, GNAQ, in blue naevi (83%) and ocular melanoma of the uvea ( 46%). The mutations occur exclusively in codon 209 in the Ras- like domain and result in constitutive activation, turning GNAQ into a dominant acting oncogene. Our results demonstrate an alternative route to MAP kinase activation in melanocytic neoplasia, providing new opportunities for therapeutic intervention.

引用

页码：599 / U108

页数：5

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