MEMORIAL SLOAN KETTERING — Right now, in your body, lurk thousands of cells with DNA mistakes that could cause cancer. Yet only in rare instances do these DNA mistakes, called genetic mutations, lead to a full-blown cancer. Why? The standard explanation is that it takes a certain number of genetic “hits” to a cell’s DNA to push a cell over the edge. But there are well-known cases in which the same set of mutations clearly causes cancer in one context, but not in another.
A good example is a mole. The cells making up a mole are genetically abnormal. Quite often, they contain a mutated version of the BRAF gene that, when found in cells located outside of a mole, will often lead to melanoma. But the vast majority of moles will never turn cancerous. It’s a conundrum that has scientists looking to cellular context for clues to explain the difference.
“We’ve known for a while that cellular context matters in cancer formation,” says Richard White, MD, PhD, a physician-scientist at MSK who studies melanoma in the lab. “But exactly how context combines with genetic mutations to promote cancer is largely unknown.”