Researchers identify melanoma-driving genes

National report - Melanoma researchers may now have a better idea of which genes damaged by ultraviolet radiation actually drive the disease.

Melanoma tumor cells are full of UV-induced genetic damage caused by sunlight exposure, but due to sheer number of these “passenger” mutations, none have been conclusively tied to the development and progression of the disease, Newswise reports.

Researchers with the Broad Institute of Harvard and Massachusetts Institute of Technology, Boston; the Dana-Farber Cancer Institute, Boston; and the University of Texas M.D. Anderson Cancer Center, Houston; created a method by which to spot the “drivers” among these passengers and identified six genes with driving mutations in melanoma, three of which have recurrent “hot spot” mutations caused by UV light.

A number of important mutations - including BRAFV600 mutations, present in half of all melanomas, and NRAS (Q61) mutations - had previously been identified as melanoma drivers. The vast majority of these mutations, however, don’t appear to be caused by direct UV damage.

The six new melanoma genes the researchers identified are all significantly mutated and provide potential targets for new treatments. The team’s analysis identified functional mutations in the well-known cancer genes BRAF, NRAS, PTEN, TP53, CDKN2A and MAP2K1. It also uncovered five new genes-RAC1, PPP6C, STK19, SNX31 and TACC1-that had not been previously recognized as significantly mutated in melanoma. The sixth new gene tied to melanoma was ARID2, an apparent tumor-suppressor gene possessing a significant number of loss-of-function mutations found in 7 percent of patient samples.

Researchers said determining whether these genes are amenable to targeted therapy, or whether their mutations predict sensitivity to currently available drugs, would be an important next step in applying the study’s findings clinically.
The study was published online July 20 in Cell.

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