KIT, GNAQ, BRAF AND RAS ONCOGENE MUTATIONS IN PATIENTS WITH UVEAL MELANOMA

Uveal melanoma is the most frequent neoplasm of the eyes (UM). Oncogenes BRAF and NRAS are frequently mutated in melanoma of the skin, but rarely in uveal melanoma. Recently it was shown that oncogenes KIT and GNAQ are activated in uveal melanoma, but rarely mutated in skin melanoma. Mutation of the gene GNAQ is the first specific mutation in uveal melanoma. New oncogene GNAQ encodes the alpha subunit of heterotrimeric G-proteins with GTPase activity. Mutant form GNAQ protein unable to hydrolyze GTP leads to constitutive activation GNAQ and MAP-kinase cascade. The genomic analysis is necessary for specific target therapy of patients with advanced uveal melanoma. Thus, imatinib mesylate was recommended for treatment of UM patients with KIT mutations, while vemurofenib was suggested for treatment of UM patients with BRAF mutations (V600E).
The aim of our study was to determine the mutations in oncogenes BRAF, NRAS, KRAS, KIT and GNAQ in DNA from uveal melanoma. Tumor DNA was isolated from fresh tumor tissue obtained during operation of 17 patients with UM. All tumor tissues were histologically verified. For mutation analysis tumor DNA was amplified in PCR with primers to the sites of the most frequent mutations in followed with the sequencing of the PCR products. There were no mutations found in oncogenes BRAF, NRAS and KRAS in UM DNA from 17 patients. Deletions in exon 11 of the gene KIT we identified in two of 17 UM cases (12%). Mutations in exon 5 GNAQ corresponding to substitutions Q209P and Q209L in GNAQ protein were found in seven cases (7/17, 41%).

GNAQ, BRAF, KIT RAS

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