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Skin Cancer Clues Revealed By Zebrafish

by Tanya Thomas on April 10, 2011 at 10:16 AM
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 Skin Cancer Clues Revealed By Zebrafish

Zebrafish has offered new hope to people with melanoma, an aggressive form of skin cancer.

Researchers identified SETDB1 as a new gene that promotes the growth of melanoma and may play a role in up to 70 percent of malignant melanomas.

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"We hope our discovery will ultimately lead to better therapeutic strategies for patients with melanoma," says study co-first author Yariv J. Houvras, assistant professor of medicine in the Departments of Surgery, Medicine, and Cell and Developmental Biology at Weill Cornell Medical College.

Houvras and colleagues created "MiniCoopR," a transposon-based vector to deliver candidate human test genes into a specially engineered strain of zebrafish that harbors a mutated BRAF gene. The researchers screened more than 3,000 zebrafish and found one gene that dramatically accelerated melanoma formation: SETDB1, which encodes a histone methyltransferase enzyme. Fish melanomas with elevated levels of SETDB1 are highly invasive and have a set of deregulated genes that are present in human tumors with high levels of SETDB1.
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The discovery that SETDB1 accelerates melanoma formation in zebrafish is important because SETDB1 appears to be frequently overexpressed in human melanomas. "SETDB1 is an enzyme, so it may be a good drug target," explains Houvras. In a second report led by first author Richard White, researchers found that the combination of leflunomide, a drug used to treat arthritis, and a BRAF inhibitor in clinical development was effective in blocking the formation of stem cells in zebrafish that give rise to melanoma.

Houvras explains that the zebrafish is becoming a popular method for investigating malignancies, including melanoma, leukemia and sarcoma.

The study was published in the journal Nature.

Source: ANI
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