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2 genetic deletions in human genome linked to the development of aggressive prostate cancer
Date:4/9/2012

y of cancer cells to grow and to invade.

Both of these variants are small deletions in DNA that lead to over-expression of genes, Dr. Demichelis says. She and her colleagues found that one gene that is over-expressed due to the variant deletion is MGAT4C, which leads to the ability of cells to grow and migrate. "A man with the variant is four times more likely to develop prostate cancer if he inherited this variant than if he did not," Dr. Demichelis says. "Interestingly, MGAT4C was found to be significantly over-expressed in metastatic versus localized prostate cancer," she adds.

The role of the other genetic variant, located in the "junk" region of the human genome, is not yet known, but the researchers believe it activates a cascade of other genes. They calculated a man is three times more likely to develop prostate cancer if he has inherited this variant.

The investigators calculated these two newly identified variants occur at a frequency of between 1.5-3 percent of the overall population, but are found at a significantly higher percentage in men diagnosed with aggressive prostate cancer. "For the gene coding variant, MGAT4C, we were able to analyze metastatic human samples where we observed that the high-risk gene is abundantly present," says Dr. Demichelis.

Now researchers are looking for other variants they hope to be able to build into a comprehensive DNA test to be used as a diagnostic tool to help clinicians identify men whose prostate cancer will likely progress to advanced stages. "We could also potentially use such a DNA test for chemoprevention if risk of developing aggressive prostate cancer is deemed to be high," says Dr. Demichelis. "This is the start of a new strategy. It would not replace PSA, but would identify other risk factors."

"In this new area of research, we are starting to appreciate that the differences in inherited genomic variants account not only for why we look different or respond in var
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Contact: Lauren Woods
law2014@med.cornell.edu
212-821-0560
New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College
Source:Eurekalert

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