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Genetic Tests Establish How Exposure To Sunlight Mutates Moles To Melanoma

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It has long been established that moles can be cancerous. A new study by international researchers shows how genetic tests can determine or predict if suspicious-looking moles can become malignant.

Researchers from the University of California San Francisco wanted to determine genetic changes that happen in skin lesions and how these turn into melanoma. Though less common than other skin cancers, the fast progression of melanoma makes it one of the deadliest cancers.

Despite accounting for just 2 percent of all skin cancers, melanoma causes a large majority of skin cancer-related deaths. Apparently, it occurs 20 times more often in fair-skinned people.

This year, an estimate of 73,870 new melanomas will be diagnosed and 9,940 people are expected to die from the disease.

The researchers found that genetic changes in moles or precursor lesions that happen for a long period of time are caused by exposure to sunlight. Ultraviolet (UV) rays can turn benign skin lesions into malignant ones, which can be very deadly.

In the study, the researchers took advantage of a unique characteristic of melanoma where the malignant lesion usually appears adjacent to a precursor lesion. They were then able to compare the genetic changes that happen in both the malignant and benign skin lesions.

Skin samples from archives containing both the precursor and malignant lesions were collected and around 293 cancer-causing genes were sequenced from the samples. The specimens were grouped by pathologists into categories such as "benign" or "invasive" based on their progression.

"What happens to patients now is totally unstandardized," senior author Dr. Boris Bastian, Cancer Research at the UCSF Helen Diller Family Comprehensive Cancer Center (HDFCCC) said in a press release.

"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," he added.

In the areas that were pathologists assessed as benign, the researchers found only a single pathogenic mutation called BRAF V600E, which has long been associated with melanoma. However, this single alteration in the BRAF gene appears to be sufficient for the formation of a mole that can possibly develop into melanoma. 

Mutations from UV damage have a unique "signature" the researchers observed in cancer-causing genes at every stage of melanoma progression. 

"It is clear from epidemiologic studies that UV radiation is a pathogenic factor promoting the development of melanoma," Dr. Bastian said in an interview.

"Our study clarifies this role, implicating UV radiation in both the formation of precursor lesions and the progression from precursor lesions to melanoma. Therefore, clinicians should continue to advise their patients to avoid the sun, and in particular, patients with numerous nevi should avoid the sun," he added.

The study was published in The New England Journal of Medicine.

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