Melanoma accounts for the vast majority of skin cancer deaths.
The main cause of melanoma, which causes around 48,000 deaths around the globe each year, is excessive exposure to ultraviolet (UV) radiation from the sun.
The Yale Cancer Center team used DNA-sequencing technologies to analyze 147 melanomas originating on both sun-exposed and sun-shielded sites on patients' bodies. They found a large number of UV-induced mutations in sun-exposed melanomas, but most of these are "passenger" mutations that don't have a functional role in melanoma.
"We devised a mathematical model to sort out the relevant DNA alterations from over 25,000 total mutations," lead study author Michael Krauthammer, an associate professor of pathology, said in a Yale news release.
The researchers pinpointed a mutation in the RAC1 gene that speeds growth and movement in normal skin pigment cells, which are where melanoma begins. The mutation likely occurs at an early stage of melanoma development and promotes cancer cell growth and spread to other sites in the body, they said.
The RAC1 mutation was found in about 9 percent of melanomas from sun-exposed skin. It is the third-most frequent mutation after previously identified BRAF and NRAS mutations. Because the RAC1 mutation is so common, it would be worthwhile to develop treatments that target it, the researchers added.
They also identified mutations that disable proteins that suppress tumours.
The study was published online July 29 in the journal Nature Genetics.
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