Publication Date:
2008-12-17
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2696133/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2696133/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Van Raamsdonk, Catherine D -- Bezrookove, Vladimir -- Green, Gary -- Bauer, Jurgen -- Gaugler, Lona -- O'Brien, Joan M -- Simpson, Elizabeth M -- Barsh, Gregory S -- Bastian, Boris C -- P01 CA025874/CA/NCI NIH HHS/ -- P01 CA025874-20A1/CA/NCI NIH HHS/ -- P01 CA025874-25A10020/CA/NCI NIH HHS/ -- P01 CA025874-280020/CA/NCI NIH HHS/ -- P01 CA025874-290020/CA/NCI NIH HHS/ -- R01 CA131524/CA/NCI NIH HHS/ -- England -- Nature. 2009 Jan 29;457(7229):599-602. doi: 10.1038/nature07586. Epub 2008 Dec 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia V6T1Z3, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19078957" target="_blank"〉PubMed〈/a〉
Keywords:
Apoptosis
;
Biopsy
;
Cell Proliferation
;
Cell Transformation, Neoplastic
;
Cells, Cultured
;
Codon/genetics
;
DNA Mutational Analysis
;
Enzyme Activation
;
GTP-Binding Protein alpha Subunits/chemistry/deficiency/*genetics/metabolism
;
Genes, Dominant/genetics
;
Humans
;
MAP Kinase Signaling System
;
Melanocytes/enzymology/pathology
;
Melanoma/enzymology/*genetics/pathology
;
Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism
;
Mutation/*genetics
;
Nevus, Blue/enzymology/*genetics/pathology
;
Oncogenes/genetics
;
Protein Structure, Tertiary
;
Skin Neoplasms/enzymology/*genetics/pathology
;
Uveal Neoplasms/enzymology/*genetics/pathology
;
ras Proteins/chemistry
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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