(HealthDay News) – Metastatic melanomas from patients with chronic sun exposure have higher mutation rates, and a single gene is mutated in 14% of metastatic melanomas, according to a study published online May 9 in Nature.
Michael F. Berger, PhD, from the Broad Institute in Cambridge, MA, and colleagues performed whole-genome sequencing of 25 metastatic melanomas and matched peripheral blood.
The researchers found that, while the average mutation rate was 30 per megabase, the rate varied from 3 to 14 when the primary tumor originated from the nonultraviolet-exposed hairless skin of the extremities, and from 5to 55 in tumors from the hair-bearing skin of the trunk. In a tumor from a patient with a history of chronic sun exposure, the mutation rate was 111 per megabase. The PREX2 gene was mutated at a rate of 14% in an independent set of 107 human melanomas, and a mutant PREX2 accelerated tumor formation in human melanocytes in vivo.
“Thus, whole-genome sequencing of human melanoma tumors revealed genomic evidence of ultraviolet pathogenesis and discovered a new recurrently mutated gene in melanoma,” Berger and colleagues conclude.