導(dǎo)致MAPK 信號作用發(fā)生組成性激發(fā)的B-Raf 和 N-Ras的突變,，已在很多種黑素瘤（包括良性的和惡性的）中以高頻率被發(fā)現(xiàn)。然而,，它們尚未在葡萄膜黑素瘤（在使眼睛產(chǎn)生顏色的細(xì)胞中產(chǎn)生）或藍(lán)痣黑素瘤（一種良性的藍(lán)-黑色痣）中被發(fā)現(xiàn),。
現(xiàn)在,，對活檢樣品進(jìn)行的一項(xiàng)基因篩選表明，這些黑素瘤亞型在G-蛋白阿爾法亞單元GNAQ上表現(xiàn)出頻繁的激發(fā)突變,，而且導(dǎo)致MAPK通道的激發(fā),。這一結(jié)果表明，GNAQ下游的信號作用成分是潛在的治療目標(biāo),。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature 457, 599-602 (29 January 2009) | doi:10.1038/nature07586
Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi
Catherine D. Van Raamsdonk1, Vladimir Bezrookove2, Gary Green2, Jürgen Bauer2,4, Lona Gaugler2, Joan M. O'Brien3, Elizabeth M. Simpson5, Gregory S. Barsh6 & Boris C. Bastian2
1 Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia V6T1Z3, Canada
2 Department of Dermatology and Comprehensive Cancer Center,
3 Department of Ophthalmology and Comprehensive Cancer Center, University of California, San Francisco, California 94143, USA
4 Department of Dermatology, University of Tübingen, Tübingen D-72076, Germany
5 Centre for Molecular Medicine and Therapeutics and Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia V6T1Z3, Canada
6 Department of Genetics, Stanford University, Stanford, California 94305, USA.
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 pathway1, 2. However, BRAF and NRAS mutations are absent in a number of other melanocytic neoplasms in which the equivalent oncogenic events are currently unknown3. Here we report frequent somatic mutations in the heterotrimeric G protein -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.
