Preventing benign moles from turning cancerous

Text by Greg Johnson

Human moles are generally similar in size, color, and shape. Usually absent at birth, they start out as tiny little dots that grow slowly for one to two years to a few millimeters, about the size of a pencil eraser, and then stop. The cells don’t die; they just exist.

Moles Melanoma

Human moles are generally similar in size, color, and shape. Usually absent at birth, they start out as tiny little dots that grow slowly for one to two years to a few millimeters, about the size of a pencil eraser, and then stop. The cells don’t die; they just exist.

A mole is medically known as a benign tumor or a benign proliferation of melanocytes, which are the cells that give human skin its pigmentation.

“Fortunately, most of the moles that folks have are innocuous and they sit there your whole life and they don’t cause problems,” says Todd W. Ridky, an assistant professor of dermatology at the Perelman School of Medicine. “Moles are probably the most common tumor on humans. Benign, but still an abnormal growth.”

Melanocytes that proliferate benignly cause moles; those that proliferate malignantly cause melanoma, a dangerous and potentially lethal form of skin cancer. Ridky says a fairly large percentage—a third, perhaps up to half—of all melanomas begin in a preexisting benign mole.

Moles Melanoma

Previous scientific studies have shown that a mutation in the BRAF gene causes abnormal melanocyte growth in the majority of moles and melanomas. Ridky says the mutation is “kind of like a gas pedal” for the BRAF gene, causing it to be “super active,” leading to the over-proliferation of melanocytes.

After a year or two of proliferating, most moles stop growing, halted by some biological brake. Long-standing, unresolved questions among dermatologists and cancer biologists have been: Why are most moles the same size, and why do they eventually stop proliferating?

Ridky and colleagues have found an answer. In a study published in the journal Cancer Discovery, they identified a major genetic factor that applies a brake to proliferating moles, and keeps them in their typical cancer- and growth-free state.

The researchers set out to determine how the human body normally stops melanocytes from growing. In order to do so, they took melanocytes from moles on human patients and compared them to melanocytes from regular human skin.

Ridky and colleagues looked at most of the major known protein factors inside cells that impact the cell cycle, or the machinery that allows cells to divide. They noticed a massive induction of the p15 protein in the mole cells. In other settings, p15 has been known to inhibit cell division.

“There was 140 times more p15 protein in the mole cells than there was in regular melanocytes,” Ridky says.

The researchers conducted several tests that confirmed that p15 is necessary and sufficient to stop the proliferation of melanocytes. In its absence, mole melanocytes develop the capability of dividing again and progressing to cancer.

“Every mole we looked at had a lot of p15 protein throughout the mole, but many of the melanomas had either depressed levels or no p15 at all,” Ridky says.

Ridky says their findings can be of great use in dermatology, and potentially affect how patients are treated. Dermatologists occasionally come across cases in which they are not entirely sure if an atypical looking mole is melanoma or not.

“A lot of times, it’s obvious, but there are cases where it’s not clear,” Ridky says. “If p15 is gone, that would be a pretty ominous sign. You’d probably want to treat that lesion more like a melanoma than you would a mole.”

If medical professionals could reintroduce p15 into cancerous melanocyte cells with low p15 levels, Ridky says tumor growth would likely be slowed or arrested. However, that technology does not currently exist.

“It’s conceivable that there could be some drug, some small molecule, that could be used to reactivate the p15 in some cases, but that’s going to require additional research,” he says.

Originally published on .