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Mar 22, 2007

Gene Mutation that May Suppress Colon Cancer Discovered

  • Cancer biologists at the Kimmel Cancer Center at Jefferson found a gene mutation that can reduce the number of colon polyps that develop, potentially cutting the risk of cancer. The finding may provide new ways to diagnose, prevent, and treat colon cancer, the scientists say.

    In experiments with mice, researchers discovered that those carrying one copy of the damaged gene Atp5a1 had about 90% fewer polyps in the small intestine and colon.

    The team studied a type of mice called 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 developing 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 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 the number of polyps—and tumors—either higher or lower and can mean a person is more prone or resistant to developing polyps and tumors.”

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

    The researcher was 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. The findings will be reported in the March 22, 2007, issue of the journal Genome Research.



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