UC San Francisco researchers have identified the sequence of genetic changes that transform benign moles into malignant melanoma in a large cohort of human skin cancer patients and have used CRISPR gene editing to recreate the steps of melanoma evolution one by one in normal human skin cells in the lab. The research identified key molecular warning signs that could be used by clinicians to catch developing cancers before they spread and could also lead to new targeted therapies.
Melanoma is most commonly triggered by exposure to ultraviolet (UV) rays in sunlight, which damages DNA, creating genetic mutations that cause skin cells to multiply and spread. Often, these cells produce benign moles, pigmented skin growths that are self-limiting in size. While most moles never turn cancerous, some can transform into malignant melanoma and rapidly spread to other parts of the body. Melanomas can almost always be successfully treated if they are caught early, but fewer than 30 percent of patients with metastatic melanoma survive more than five years, making melanoma the deadliest form of skin cancer.
The new research, published July 9, 2018, in two companion papers in Cancer Cell, for the first time systematically traced how new mutations and changes in
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