Mutations in GNA11 in Uveal Melanoma

• Published in: The New England journal of medicine Vol. 363; no. 23; pp. 2191 - 2199
• Main Authors: Van Raamsdonk, Catherine D, Griewank, Klaus G, Crosby, Michelle B, Garrido, Maria C, Vemula, Swapna, Wiesner, Thomas, Obenauf, Anna C, Wackernagel, Werner, Green, Gary, Bouvier, Nancy, Sozen, M. Mert, Baimukanova, Gail, Roy, Ritu, Heguy, Adriana, Dolgalev, Igor, Khanin, Raya, Busam, Klaus, Speicher, Michael R, O'Brien, Joan, Bastian, Boris C
• Format: Journal Article
• Language: English
• Published: Waltham, MA Massachusetts Medical Society 02.12.2010
• Subjects: Animals; Biological and medical sciences; Cell culture; Cells, Cultured; DNA Mutational Analysis; Exons - genetics; General aspects; GTP-Binding Protein alpha Subunits - genetics; GTP-Binding Protein alpha Subunits, Gq-G11; Humans; Medical sciences; Melanocytes; Melanoma - genetics; Melanoma - mortality; Melanoma - secondary; Mice; Mutation; Neoplasm Transplantation; Nevus - genetics; Nevus - mortality; Nevus, Blue - genetics; Nevus, Blue - mortality; Ophthalmology; Prognosis; Proteins; Survival Analysis; Tumors; Tumors and pseudotumors of the eye, orbit, eyelid, lacrimal apparatus; Uveal Neoplasms - genetics; Uveal Neoplasms - mortality; Medicine; Eye disease; Genetics; Uvea disease; Malignant tumor; Mutation; Cancer; Uveal malignant melanoma
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJMoa1000584

A specific amino acid in the Gα 11 subunit of heterotrimeric G proteins was mutated in 32% of primary uveal melanomas and in 57% of uveal melanoma metastases analyzed in this study. This variant was found to activate the mitogen-activated protein kinase pathway. Uveal melanoma is a neoplasm that arises from melanocytes of the choroid plexus, ciliary body, and iris of the eye. 1 Unlike cutaneous melanoma, uveal melanoma lacks mutations in BRAF, NRAS, or KIT 2 – 5 and has characteristic cytogenetic alterations 6 and a strong tendency to metastasize to the liver. 1 , 7 The nevus of Ota, a subtle intradermal proliferation of melanocytes resulting in bluish-gray hyperpigmentation in the sclera and periorbital dermis, is a risk factor for uveal melanoma. 8 In mice, germline mutations that increase the activity of the closely related GTPases, Gα q (V179M) and Gα 11 (I63V), cause dermal hyperpigmentation. 9 The microscopical . . .