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Abnormalities in new molecular pathway may increase breast cancer risk
Date:6/17/2013

PHILADELPHIA A new molecular pathway involving the gene ZNF365 has been identified and abnormalities in that pathway may predict worse outcomes for patients with breast cancer, according to data published in Cancer Discovery, a journal of the American Association for Cancer Research.

"Genomic instability is an increased tendency for abnormal changes in DNA, like the addition of extra copies of chromosomes, DNA breaks and mutations," said Ji-Hye Paik, Ph.D., assistant professor in the Department of Pathology and Laboratory Medicine at Weill Cornell Medical College in New York, N.Y. "Because these genetic abnormalities increase the chances for developing a tumor, it is fundamentally important to understand the molecular basis of genomic instability in cancer for prognosis and therapy."

Telomeres are segments at the end of the chromosome that protect the chromosome from deterioration. As the length of the telomeres shortens, they activate cell death, mediated by the tumor suppressor gene, p53. This process is critical in the suppression of cancer, and dysfunctional telomeres can cause chromosomal abnormalities and cancer.

Using cells designed to be cancer-prone because of defective telomeres, Paik and colleagues demonstrated that p53 activates ZNF365 to maintain genomic stability. The researchers found that cells deficient in ZNF365 showed signs of incomplete doubling of DNA, causing abnormal cell division and unequally divided chromosomes. They concluded that because ZNF365 promotes the timely resolution of cell division, its loss led to an abnormal number of chromosomes called aneuploidy, which is implicated in many diseases including cancer.

"Our study is the first to demonstrate molecular mechanisms underlying the p53ZNF365telomere pathway and to show how alterations in this pathway may lead to increased cancer risk," said Paik. "Understanding this pathway provides novel therapeutic opportunities for cancers."


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Contact: Jeremy Moore
jeremy.moore@aacr.org
215-446-7109
American Association for Cancer Research
Source:Eurekalert

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