Moles are benign tumors found on the skin of almost every adult. Scientists have known for years that a mutation in the BRAF gene makes them start growing, but until now haven’t understood why they stop. Now, researchers from the Perelman School of Medicine at the University of Pennsylvania have identified a major genetic factor that keeps moles in their usual non-cancerous, no-growth state. The study was published online first this summer in the journal Cancer Discovery.

“The BRAF mutation that stimulates the initial growth of moles also stimulates the production of a tumor suppressor protein, p15, which ultimately acts as a powerful brake on further cell division,” said senior author Todd W. Ridky MD, PhD, an assistant professor of Dermatology at Penn. “It’s this cell division that ultimately allows the transition from a normal mole into melanoma. When mole cells lose the p15 brake, cells can start dividing again and can progress into cancer.”

For their study, Ridky and his colleagues developed a new model of human melanoma, using tissue engineering to make skin grafts containing human mole cells in which p15 was removed. When combined with other mutations known to be important for the development of melanoma, and transplanted into mice, the p15 depleted cells progressed into melanoma.

“The model tissues are medically relevant because they used the naturally occurring human mole cells in the 3-dimensional environment of living skin, which allows detailed functional studies – the field hasn’t had an experimental system like this before,” said lead author Andrew McNeal, a research specialist in Ridky’s lab.