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Researchers Fish for Clues to Cancerous Moles

Study in zebrafish yields genetic answers

TUESDAY, Feb. 8, 2005 (HealthDay News) -- Research in fish is shedding new light on how human skin moles develop into the deadly skin cancer melanoma.

Studying zebrafish, scientists at Children's Hospital Boston and the Dana-Farber Cancer Institute found that a specific mutation in a gene called BRAF is essential to mole development. When combined with another mutation in a gene called p53, moles developed into melanoma.

The findings are outlined in the Feb. 8 issue of the journal Current Biology.

Previous research found that the BRAF gene is mutated in about 75 percent of melanomas. But its role in causing this form of cancer wasn't clear.

In this study, scientists focused on genetically engineered zebrafish, an ideal candidate for genetic research since its genome is fully mapped and resembles that of humans. Female zebrafish can also give birth to more than 300 babies per week, allowing researchers to track genes as they are passed on.

The Boston team engineered zebrafish to produce the mutated form of human BRAF. These fish developed black-pigmented moles on their skin but did not develop melanoma.

However, when the fish were also engineered to be deficient in the p53 gene, which normally suppresses tumor growth, moles developed into invasive melanomas.

When cells from these tumors were injected into healthy zebrafish, they also developed melanomas, the researchers add

"We now know that BRAF, when activated, is sufficient to make moles. 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," researcher Dr Leonard Zon said in a prepared statement.

He and his colleagues plan to search for gene mutations other than the p53 mutation that may also play a role in turning moles in melanoma.

"Some of these genes may lead us to excellent pharmaceutical targets for treatment of melanoma," Zon said.

More information

The American Academy of Family Physicians has more about melanoma.

SOURCE: Children's Hospital Boston, news release, Feb. 7, 2005
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