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Genetic Tests Show How Sunlight Turns Moles into Melanoma

A doctor examines a mole PA Wire

Researchers have found a new way to tell if a suspicious-looking mole is about to turn malignant by looking at its genetic changes.

And they’ve confirmed that people who have moles should not let the sun get on them. Ultraviolet radiation from the sun directly causes the genetic mutations that finally tip a mole over into becoming melanoma, they report in the New England Journal of Medicine.

“Ultraviolet radiation turns moles into melanoma,” said Dr. Boris Bastian of the University of California San Francisco, a pathologist who helped lead the study.

“Moles don’t belong in the sun.”

Bastian and colleagues dove into a collection of moles that had turned malignant taken from 37 patients around the world. They sequenced the DNA in the tumors and compared it to DNA from healthy tissue that’s almost always taken from around the tumor to make sure all the cancer cells are removed.

“Moles don’t belong in the sun.”

Moles have a genetic mutation that makes them moles, but it’s not dangerous. “The melanomas invariably had additional genetic mutations,” said Bastian.

What they also found was that the mutations build up over time. They found extra mutations in parts of the mole that had not yet turned cancerous.

“What we have shown is those alterations can be found in the benign precursors,” Bastian said.

That means melanoma is similar to other forms of cancer, such as colon cancer or cervical cancer, which start with benign growths that can progress to cancer.

Skin cancer experts had disagreed over whether there was an intermediate stage in melanoma, between a normal harmless mole and a malignancy. This study shows there is one, and it’s determined by how many mutations there are and what kind of mutations there are.

Image: A cancerous mole
A cancerous mole depicted in a study done at the University of California San Francisco Boris Bastian / University of California San Francisco

Normal moles had a mutation called BRAF V600E, the team found. The moles then acquired more and more mutations before they became cancerous.

And there’s one cause.

“What we can find is these secondary and tertiary mutations that came after the mole formed and that make the mole progress to melanoma are caused by radiation,” Bastian said.

“The overwhelming majority of moles do not turn into melanoma. You need all the pathogenic mutations, and you have to have all those mutations in the same cell. That is highly unlikely to occur.”

But one thing does make it more likely to happen— sunlight. “By exposing yourself to UV radiation, you are forcing your bad luck,” Bastian said.

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Researchers have long known that people with more moles are more likely to develop melanoma. And they know sunlight causes most cases of melanoma.

Melanoma is the deadliest form of skin cancer. According to the National Cancer Institute, 74,000 Americans will be diagnosed with melanoma and nearly 10,000 will die from it this year.

Bastian hopes genetic tests may be used to save people from having big chunks of skin removed if they have an ugly mole.

“By exposing yourself to UV radiation, you are forcing your bad luck."

“Right now we practice defensive medicine,” Bastian said. “When in doubt, cut it out.”

It could also save people who have melanoma that’s not obvious. If a dermatologist removes a suspicious-looking mole that doesn’t turn out to be cancer, but that has mutations that show it’s well on its way to becoming cancer, doctors may take more precautions — removing more of the surrounding tissue, to be safe, and testing nearby lymph nodes to be sure that cancer hasn’t developed and spread.

Two experts on the genetic testing of tumors, Dr. Bert Vogelstein and Dr. Kenneth Kinzler of the Howard Hughes Medical Institute and Johns Hopkins University, said genetic tests like these are starting to open new ways to catch cancer earlier – and to treat it more effectively.

Newer drugs target the genetic mutations that make tumors dangerous, instead of just killing cells wholesale.

“It's a whole new ball game,” they wrote in a commentary on the findings