Shanika Jayasinghe, a geneticist at QIMR Berghofer in Brisbane, once examined a dataset of 85,000 people’s DNA and found something remarkable: 24 new genetic regions linked to mole count—each one a potential clue in the puzzle of melanoma. This discovery, part of the world’s largest genetic study of “moliness,” has uncovered over 250 key genes tied to both moles and melanoma, opening new doors in the fight against Australia’s most lethal skin cancer. Published in Nature Communications, the research shifts focus from sun exposure—the well-known villain—to the hidden genetic drivers behind why some people develop dozens of moles, and why some of those moles turn deadly.
Melanoma claims about 1,400 Australian lives each year, despite decades of SunSmart campaigns and advances in immunotherapy. "We know how to reduce sun exposure and risk through SunSmart behaviors, and new immunotherapies have greatly improved survival rates. But people still get melanoma and people still die from melanoma," says Associate Professor Matthew Law, head of QIMR Berghofer’s Genetics and Skin Cancer Lab. His team’s breakthrough lies in recognizing that moles and melanomas share the same origin: pigment-producing melanocytes. While moles stop growing on their own, melanomas don’t—and the genetic switch that controls this difference is now coming into focus.
The study identified 24 new genetic regions influencing mole count, a fivefold leap from the five previously known. All but one of these regions are also linked to melanoma risk. Among the most intriguing discoveries is the gene SIKE1, which normally helps regulate immune responses to viruses. When faulty, it may weaken the body’s ability to detect and destroy abnormal melanocyte growth—essentially allowing melanoma to sneak past immune defenses. This insight could lead to a new class of immunotherapies designed not just to treat, but to prevent melanoma before it starts.
The team has already used their findings to develop a Polygenic Risk Score (PRS) for moliness—a tool that could one day help doctors identify high-risk individuals earlier, enabling more frequent monitoring and earlier intervention. With about a third of melanomas arising from pre-existing moles, such precision could be life-saving. The researchers are now expanding their search, analyzing even larger datasets and screening existing drugs that might target these newly discovered pathways.
"I'm really proud to be continuing this long legacy of research," says Jayasinghe, whose work builds on QIMR Berghofer’s decades of leadership in skin cancer genetics. As the genetic map of melanoma grows clearer, so does the hope of turning one of Australia’s biggest health challenges into a preventable condition.