Frequent Somatic Mutations of GNAQ in Uveal Melanoma and Blue Naevi

Overview

Journal Nature

Specialty Science

Date 2008 Dec 17

PMID 19078957

Citations 685

Authors

Catherine D Van Raamsdonk

Vladimir Bezrookove

Gary Green

Jurgen Bauer

Lona Gaugler

Joan M OBrien

Elizabeth M Simpson

Gregory S Barsh

Boris C Bastian

Affiliations

Soon will be listed here.

Abstract

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. However, BRAF and NRAS mutations are absent in a number of other melanocytic neoplasms in which the equivalent oncogenic events are currently unknown. 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.

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