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, has been identified in a major international study.
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 by researchers from the U.S., the U.K. and Australia identified a mechanism by which MITF mutation could increase melanoma risk.
Another study from French researchers found that the same mutation increased the risk for the most common form of kidney cancer, for melanoma or for both tumours.
“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,” said David Fisher, MD, PhD, chief of Dermatology at Massachusetts General Hospital (MGH), director of the MGH Cutaneous Biology Research Center and co-senior author of the study.
“The currently discovered mutation appears to block sumoylation of MITF, and the resulting overactivity of MITF significantly increases melanoma risk,” he added.
The MITF mutation – designated E318K – was also associated with increased numbers of the common skin moles called nevi, a recognized risk factor for melanoma, and with a reduced likelihood of blue eye colour.
The finding is expected to appear in Nature.