New Genetic Study Strengthens Link Between UV Radiation and Melanoma

A new study appearing in the journal Nature greatly reinforces the findings of an earlier landmark genetic study linking damage from the sun’s ultraviolet rays (UVR) to melanoma, the deadliest form of skin cancer. In 2009, researchers out of Hinxton, England, used new molecular technology to examine the complete genetic material (the genome) of a melanoma taken from a patient with the disease, identifying thousands of mutations (genetic flaws) caused by damage from solar UVR. The study has been seen as the greatest evidence to date that UVR causes genetic damage that may lead to melanoma.

Now, researchers at Harvard and MIT have studied the genomes of 25 melanoma patients. They discovered a specific gene, PREX2, that was damaged and mutated in 11 of the 25 genomes. They observed, furthermore, that the amount of mutations in this gene was directly linked to chronic UV exposure; the more exposure patients had, the more mutations they had in PREX2, apparently confirming the role of sun damage in melanoma development. PREX2 mutations have occasionally been reported in colon, lung, and pancreatic cancer, and frequently reported in breast cancers; they have been found to accelerate tumor formation in human melanocytes (the pigment cells where melanomas develop).

PREX2 normally interacts with a certain tumor-suppressing protein; UV damage may cause changes in PREX2 that allow the protein to turn from a tumor suppressor into a tumor promoter, thereby leading to melanoma.  

“We still can’t say we know exactly how it works,” says Levi A. Garraway, senior coauthor of the study. “But PREX2 may be a very new category of mutated cancer genes that point us to at least one and maybe more pathways worth targeting therapeutically in melanoma.”    

Professor Mark Middleton, director of Cancer research UK’s Experimental Cancer Medicine Center at the University of Oxford, said that the study highlighted the important role played by sun damage in melanoma, and emphasized the need to follow simple sun safety measures such as shade, clothing, and SPF15+ sunscreen.