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Jan 4, 2008

Number of Gene Copies Effect Cancer Risk

  • The number of copies of a particular gene can affect the severity of colon cancer in a mouse model, according to investigators at Johns Hopkins and Ohio State University.

    The research team started with a mouse model that carries, rather than a whole extra copy of chromosome 21 as is seen in trisomy 21, or Down syndrome, a partial copy containing 108 genes. They then mated those trisomic mice to mice that carry a mutation that causes intestinal tumors, similar to those seen in colon cancer in humans. The trisomic, colon cancer mice had 44% fewer intestinal tumors compared to the colon cancer mice without the extra 108 genes.

    The investigators then used another mouse model of Down syndrome, one that carries extra copies of only 33 genes on chromosome 21, and repeated their genetic crosses. Mice with three copies of the 33 genes developed half the number of tumors as mice with the standard two copies. Mice carrying a deletion that left them with only one copy of these 33 genes developed twice the number of tumors as usual.

    The scientists then focused on one gene, Ets2, which previously has been implicated as a cause of cancer. Some research suggested, however, that Ets2 activity might be involved in pathways that cause cells to die.

    The team then repeated their genetic crosses, this time with mice that had three, two, or one copy of the Ets2 gene only. Once again, mice that were trisomic for 33 genes including Ets2 had fewer tumors. Mice that were trisomic for 32 of these genes but had the normal two copies of Ets2, though, had a tumor number similar to control mice. Mice with just one copy of Ets2 developed more tumors.

    The study was published in the January 3 issue of Nature.



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