导致MAPK 信号作用发生组成性激发的B-Raf 和 N-Ras的突变，已在很多种黑素瘤（包括良性的和恶性的）中以高频率被发现。然而，它们尚未在葡萄膜黑素瘤（在使眼睛产生颜色的细胞中产生）或蓝痣黑素瘤（一种良性的蓝-黑色痣）中被发现。
现在，对活检样品进行的一项基因筛选表明，这些黑素瘤亚型在G-蛋白阿尔法亚单元GNAQ上表现出频繁的激发突变，而且导致MAPK通道的激发。这一结果表明，GNAQ下游的信号作用成分是潜在的治疗目标。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
