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Ever wonder what genetic switch is flipped that turns a harmless mole into a potentially deadly melanoma? Researchers at Children's Hospital Boston and the Dana-Farber Cancer Institute did, and are using the tiny zebrafish—fast becoming a research subject of choice because of their genetic similarity to humans—to find an answer.
Leonard Zon, MD, Elizabeth Patton, PhD, and colleagues genetically engineered zebrafish with a mutation in a gene called BRAF that is critical to mole development. The fish developed black-pigmented moles on their skin, but not melanoma. When they were also made to be deficient for a gene called p53, which suppresses tumor growth, the moles developed into invasive melanomas resembling human cancers. And when cells from these tumors were injected into healthy zebrafish, they too developed melanomas.
Now that the zebrafish model has been created, Zon's team will use it to examine how melanomas metastasize, look for other gene mutations besides p53 that transform moles into malignant melanomas, test the effects of risk factors for human melanoma and how they interact with gene mutations to cause disease, and test potential anti-melanoma drugs. "Some of these genes may lead us to excellent pharmaceutical targets for treatment of melanomas," Zon says.
Finding an effective way to study human melanoma is especially important since its incidence is rising faster than any other cancer, doubling every 10 to 20 years. When melanoma spreads to other organs, the average life expectancy is only six to 10 months. The paper announcing the results of the study appeared in the February 8 issue of Current Biology.