Journal
NATURE
Volume 457, Issue 7229, Pages 599-U108Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nature07586
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Funding
- National Cancer Institute [P01 CA025874 Project 2]
- Melanoma Research Alliance, the Canadian Institutes of Health Research [MOP-79511]
- National Institutes of Health
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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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