期刊
NATURE
卷 457, 期 7229, 页码 599-U108出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nature07586
关键词
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资金
- National Cancer Institute [P01 CA025874 Project 2]
- Melanoma Research Alliance, the Canadian Institutes of Health Research [MOP-79511]
- National Institutes of Health
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.
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