Sunlight causes genetic mutations that turn moles malignant

Continued sunlight exposure can push moles to turn malignant from induced genetic mutations, says a study. It found a distinct signature in cancer-causing genes at every stage of melanoma progression from precursor skin lesions to malignant skin cancer. Melanoma like some other forms of cancer starts with benign growths that can progress to cancer, found the study.

"This study shows that they (mutations) occur in benign moles, in the melanoma that arises from these moles, and in intermediate lesions. UV both initiates and causes the progression of melanoma, so exposing even benign moles to the sun is dangerous," said Boris Bastian, the Gerson and Barbara Bass Bakar Distinguished Professor of Cancer Research at the UC San Francisco Helen Diller Family Comprehensive Cancer Center.

The research reaffirms the role of sun exposure in the emergence of precursor lesions, and also suggests that continued ultraviolet radiation damage to benign precursor lesions may push them towards malignancy. By studying the lesions for mutations, scientists can predict where a mole is headed.

The study clearly shows there is an intermediate stage for skin lesions between a mole and malignancy and it is determined by the number and types of genetic mutations. This has been hotly debated among dermatologists and pathologists.

Three stages

The team led by A Hunter Shain, PhD, a postdoctoral fellow in the Bastian laboratory gathered skin samples containing both melanoma and the precursor lesions from around it, taken from 37 patients around the world. They sequenced the DNA for 293 cancer causing genes in both types.

They found that mutations build up over time. They also found extra mutations in parts of the mole that had not yet turned cancerous. "Some doctors consider these 'intermediate' types of lesions to be entirely benign, or shave off only part of the lesion and leave some behind. But others treat it as an early melanoma. This work should open the door to understanding how risky these lesions are and when they should be completely removed," said Bastian.

In all of the 13 areas that were assessed as benign by the pathologists, the researchers found only a single pathogenic mutation, one called BRAF V600E, long associated with melanoma.
However, in most intermediate lesions, BRAF mutations were accompanied by additional mutations, but not the full set observed in invasive melanoma.

Moreover, while the researchers found more point mutations in intermediate lesions than in benign moles, there were far fewer point mutations in intermediate lesions than in invasive melanomas, and copy-number alterations were rare. This showed the intermediate stage as a distinct stage.

"Kids who are in the sunlight more tend to have a greater number of benign moles, and if they continue to stay in the sunlight, those moles are more likely to progress to melanoma," Shain said. "This study shows that UV-radiation-induced mutations start to accumulate before a benign mole forms, and that UV-radiation-induced mutations continue to drive the progression of some benign and intermediate lesions towards melanoma. So exposing even benign moles to UV is not without risk."

Melanoma is the deadliest form of skin cancer. According to the National Cancer Institute, 74,000 Americans will be diagnosed with melanoma and around 10,000 will die from it in 2015. The study is published in the New England Journal of Medicine.