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Jefferson scientists uncover gene mutation that cuts colon polyps

22.03.2007
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 cell’s 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.”

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In earlier work, the husband and wife team had identified the general region on the chromosome for the mutation. “Now, we’ve identified the gene and it’s very important – it encodes a subunit of the ATP synthase protein, which is known as the molecular motor in the mitochondria, and responsible for the production of ATP and energy in cells,” says Dr. Buchberg. They have dubbed Atp5a1 “Mom2,” for Modifier of Min 2 gene, having previously identified the first modifier of Min mice, Mom1.

“No one as far as we know has ever found a mutation in this gene,” says Dr. Siracusa, noting that both gene mutations – Apc and Atp5a1 – are on mouse chromosome 18. “If the other normal chromosome is lost for some reason, or mice have two copies of the mutant Atp5a1, they die in embryonic development, presumably because the cells lack an energy source.”

The corresponding human gene, ATP5A1, is also located on chromosome 18, in a region that sometimes shows genetic mutations in colon tumors.

Steve Benowitz | EurekAlert!
Further information:
http://www.jefferson.edu

Further reports about: Atp5a1 Chromosome Mutation colon polyps

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