Two Gene Mutations Linked to Melanoma of the Eye

Researchers have elucidated mechanisms of two gene mutations associated with uveal melanoma, identified a therapeutic target for treating uveal melanoma in adults, and provided evidence that an existing therapy can be used to slow eye tumor growth.

The presence of one of two gene mutations approximately 70 percent of all tumors has led researchers to assume a genetic association with uveal melanoma. Now researchers have shown that the two genes implicated – GNAQ and GNA11 (they code for G proteins that normally function as molecular on-off switches)—have mutations that shift the G proteins to a permanent “on” or active status, which results in over-activation the Yes-associated protein (YAP). The activation of the YAP protein induces uncontrolled cell growth and inhibits cell death, causing malignancies.

Earlier research by other scientists has shown that the drug verteporfin, used to treat abnormal blood vessel formation in the eye, acts on the YAP pathway inhibiting the protein's YAP function. The UC San Diego-led team showed that in mouse models verteporfin also suppresses the growth of uveal melanoma tumors derived from human tumors. Kun-Liang Guan, PhD, professor of pharmacology at UC San Diego Moores Cancer Center and co-author of the study said in a statement, "The genetics of this cancer are very simple and our results have clear implications for therapeutic treatments for the disease."

The findings are published online in the May 29 issue of the journal Cancer Cell.