A major international study has identified a novel gene mutation that appears to increase the risk of both inherited and sporadic cases of malignant melanoma, the most deadly form of skin cancer. The identified mutation occurs in the gene encoding MITF, a transcription factor that induces the production of several important proteins in melanocytes, the cells in which melanoma originates. While previous research has suggested that MITF may act as a melanoma oncogene, the current study identifies a mechanism by which MITF mutation could increase melanoma risk. The report from researchers from the U.S., the U.K., and Australia was published online in Nature on November 13, 2011. It is expected to appear in a print issue along with a study from French researchers finding that the same mutation increased the risk for the most common form of kidney cancer, for melanoma, or for both tumors. "We previously knew that MITF is a master regulator for production of the pigment melanin; and several years ago we identified a chemical modification, called sumoylation, that represses MITF activity," says Dr. David Fisher, chief of Dermatology at Massachusetts General Hospital (MGH), director of the MGH Cutaneous Biology Research Center and co-senior author of the Nature paper. "The currently discovered mutation appears to block sumoylation of MITF, and the resulting overactivity of MITF significantly increases melanoma risk." While approximately 10 percent of patients with melanoma report a family history of the disease, true hereditary melanoma, involving multiple cases across many generations, probably accounts for 1 percent or less of all cases, says co-senior author Dr. Hensin Tsao, of MGH Dermatology and the Wellman Center for Photomedicine.
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