When Does A Mole Become A Melanoma?14 years ago
Posted on Feb 21, 2005, 6 a.m.
By Bill Freeman
Researchers at Children's Hospital Boston and the Dana-Farber Cancer Institute have found an important clue about the origins of the deadly skin cancer melanoma. Using black-and-white-striped zebrafish to model human melanoma, they showed that a specific mutation in a gene called BRAF is critical to the development of moles, and when combined with a separate mutation, leads to cancer.
Melanoma is now an epidemic cancer: its incidence is rising faster than that of any other cancer, doubling every 10-20 years. When melanoma is metastatic, or spreads to other organs, the average life expectancy is only 6-10 months. Previous studies have indicated that the BRAF gene is mutated in about 75 percent of melanomas, but until this study, no one knew its role, if any, in causing the cancer.
Dr. Leonard Zon, a Howard Hughes Medical Institute investigator in the Children's/Dana-Farber Division of Hematology/Oncology, postdoctoral fellow Dr. Elizabeth Patton, and colleagues genetically engineered zebrafish to make the mutated form of human BRAF. The mutant fish developed black-pigmented moles on their skin, but none developed melanoma. When the fish were also made to be deficient for a gene called p53, which suppresses tumor growth, the moles developed into invasive melanomas resembling human cancers. When cells from these tumors were injected into healthy zebrafish, they too developed melanomas. ''We now know that BRAF, when activated, is sufficient to make moles,'' says Zon. ''We also know that it's insufficient to make cancer - you need other mutations, like a deficiency in the p53 tumor suppressor gene, to get melanoma.''