Study Probes Mutations That Underlie Uveal Melanoma

Most uveal melanomas have somatic mutations in GNAQ or GNA11, pointing to role in development

THURSDAY, Nov. 18 (HealthDay News) -- Most uveal melanomas and blue nevi may have mutations in GNAQ -- which encodes an alpha subunit of heterotrimeric G proteins -- or GNA11, a paralogue of GNAQ, according to research published online Nov. 17 in the New England Journal of Medicine.

Catherine D. Van Raamsdonk, Ph.D., of the University of British Columbia in Vancouver, Canada, and colleagues analyzed data generated from sequencing exon 5 of GNAQ and GNA11 in 713 different types of melanocytic neoplasms, including uveal melanomas and blue nevi.

The researchers found that 83 percent of uveal melanomas had a constitutively active mutation in GNAQ or GNA11. Somatic mutations were seen in exon 5, which affected Q209, and exon 4, which affected R183, in GNAQ and GNA11 in a mutually exclusive manner. Q209 mutations were more prevalent in GNAQ or GNA11 than mutations affecting R183. In a mouse model, mutations in GNA11 were linked to spontaneously metastasizing tumors and activation of the mitogen-activated protein kinase pathway.

"Because mutation of GNA11 or GNAQ is not sufficient on its own to induce malignant transformation, aberrations in other pathways are probably critical to the genesis of uveal melanoma. The identification of these pathways would be a useful next step," write the authors of an accompanying editorial.

One study author disclosed a financial relationship with Alnylam Pharmaceuticals, involving patents for the use of GNAQ and GNA11 in melanoma.

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