Medizinische Universität Graz - Research portal

Go directly to the nagivation.
Go directly to the content.

Navigation/Search

Selected Publication:

SHR Neuro Cancer Cardio Lipid Metab Microb

Van Raamsdonk, CD; Griewank, KG; Crosby, MB; Garrido, MC; Vemula, S; Wiesner, T; Obenauf, AC; Wackernagel, W; Green, G; Bouvier, N; Sozen, MM; Baimukanova, G; Roy, R; Heguy, A; Dolgalev, I; Khanin, R; Busam, K; Speicher, MR; O'Brien, J; Bastian, BC.
Mutations in GNA11 in Uveal Melanoma.
N ENGL J MED. 2010; 363(23): 2191-2199. Doi: 10.1056/NEJMoa1000584 [OPEN ACCESS]
Web of Science PubMed FullText FullText_MUG

Co-authors Med Uni Graz: Obenauf Anna Christina; Speicher Michael; Wackernagel Werner; Wiesner Thomas
Altmetrics:
Dimensions Citations:
Plum Analytics:
Scite (citation analytics):
Abstract:: Uveal melanoma is the most common intraocular cancer. There are no effective therapies for metastatic disease. Mutations in GNAQ, the gene encoding an alpha subunit of heterotrimeric G proteins, are found in 40% of uveal melanomas. We sequenced exon 5 of GNAQ and GNA11, a paralogue of GNAQ, in 713 melanocytic neoplasms of different types (186 uveal melanomas, 139 blue nevi, 106 other nevi, and 282 other melanomas). We sequenced exon 4 of GNAQ and GNA11 in 453 of these samples and in all coding exons of GNAQ and GNA11 in 97 uveal melanomas and 45 blue nevi. We found somatic mutations in exon 5 (affecting Q209) and in exon 4 (affecting R183) in both GNA11 and GNAQ, in a mutually exclusive pattern. Mutations affecting Q209 in GNA11 were present in 7% of blue nevi, 32% of primary uveal melanomas, and 57% of uveal melanoma metastases. In contrast, we observed Q209 mutations in GNAQ in 55% of blue nevi, 45% of uveal melanomas, and 22% of uveal melanoma metastases. Mutations affecting R183 in either GNAQ or GNA11 were less prevalent (2% of blue nevi and 6% of uveal melanomas) than the Q209 mutations. Mutations in GNA11 induced spontaneously metastasizing tumors in a mouse model and activated the mitogen-activated protein kinase pathway. Of the uveal melanomas we analyzed, 83% had somatic mutations in GNAQ or GNA11. Constitutive activation of the pathway involving these two genes appears to be a major contributor to the development of uveal melanoma. (Funded by the National Institutes of Health and others.).
Find related publications in this database (using NLM MeSH Indexing): Animals -; Cells, Cultured -; DNA Mutational Analysis -; Exons - genetics; GTP-Binding Protein alpha Subunits - genetics; Humans -; Melanocytes -; Melanoma - genetics Melanoma - mortality Melanoma - secondary; Mice -; Mutation -; Neoplasm Transplantation -; Nevus - genetics Nevus - mortality; Nevus, Blue - genetics Nevus, Blue - mortality; Prognosis -; Survival Analysis -; Uveal Neoplasms - genetics Uveal Neoplasms - mortality