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Jefferson scientists uncover gene mutation that cuts colon polyps, may suppress cancer

(PHILADELPHIA) Cancer biologists at the Kimmel Cancer Center at Jefferson have found a gene mutation that can dramatically reduce the number of colon polyps that develop, and in turn, potentially cut the risk of cancer.

In experiments with mice genetically prone to develop polyps, researchers discovered that animals carrying one copy of the damaged gene, Atp5a1, had about 90 percent fewer polyps in the small intestine and colon. Because people with large numbers of such polyps are at significantly higher risk to develop colon cancer, the finding may provide new ways to diagnose, prevent and treat colon cancer, the scientists say. They report their findings March 22, 2007 online in the journal Genome Research.

The researchers, led by Arthur Buchberg, Ph.D., and Linda Siracusa, Ph.D., both associate professors of microbiology and immunology at Jefferson Medical College of Thomas Jefferson University in Philadelphia, studied a type of mice called Min (multiple intestinal neoplasia). Such mice carry mutations in the Apc gene, which causes the development of intestinal tumors in mice. An alteration in the corresponding human gene, APC, is the first step in most cases of the development of colon polyps and the majority of colorectal cancers.

It turns out that Atp5a1, which is crucial for the cells energy production, is also a modifier gene. Modifier genes play roles in individual susceptibility to cancers. Modifier genes alter a phenotype dictated by other genes, explains Dr. Siracusa. If a person inherits a mutation in the APC gene, a modifier gene can make that number of polyps and tumors either higher or lower, and can mean a person is more prone or resistant to developing polyps and tumors.

In earlier work, the husband and wife team had identified the general region on the chromosome for the mutation. Now, weve identified the gene and its very important it encodes a subunit of the ATP synthase protein, which is kn
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Contact: Steve Benowitz
steven.benowitz@jefferson.edu
215-955-5291
Thomas Jefferson University
21-Mar-2007


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