Zebrafish model reveals skin cancer-promoting gene

March 24th, 2011 - 5:07 pm ICT by ANI  

University of Massachusetts London, Mar 24 (ANI): You might have never thought that the dark stripes on the tiny zebrafish hold a key clue for discovering a treatment for the deadly skin cancer melanoma.

Now, Craig Ceol, assistant professor of molecular medicine at the University of Massachusetts Medical School, and collaborators at several institutions, have identified the melanoma-promoting gene SETDB1, by using a zebrafish model of the disease.

“We’ve known for some time that there are a number of genes that are responsible for the promotion and growth of melanoma,” said Ceol.

“With existing methods, it had been difficult to identify what those genes are. By developing a new approach, we were able to isolate SETDB1 as one of those genes,” he added.

Approximately 60 percent of human melanoma cases are caused by a mutation in the BRAF gene that drives proliferation of melanocytes, the cells responsible for skin pigmentation.

Ceol and colleagues set out to locate other genes implicated in this disease by focusing on areas of the genome that were over-represented in melanoma cells, hypothesizing that there were genes in these regions that enabled cells to grow unchecked, leading to cancerous tumors.

To evaluate genes from an over-represented region of chromosome 1, Ceol created a technique called MiniCoopR to deliver the test genes, one-by-one, to transgenic zebrafish models with the melanoma-causing BRAF mutation.

These fish also lacked the tumour suppressing gene p53.

The researchers, after painstakingly analysing more than 2,100 tumours from more than 3,000 zebrafish, found that in fish with the SETDB1 gene, melanoma not only appeared earlier, but also grew faster and invaded more deeply into the neighbouring muscle and spinal tissue.

With this new information, researchers screened 100 human melanomas for the SETDB1 gene.

In 70 percent of the sample tumours, SETDB1 was present at high levels, indicating that SETDB1 may be involved in the formation of a majority of human melanomas.

Further analysis showed that SETDB1 produces an enzyme that turns other genes on or off and is over-represented in other forms of cancer, such as ovarian, breast and liver cancer.

The discovery has been detailed in the March 24 issue of Nature. (ANI)

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