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Mutant gene identified that causes abnormal chromosome count, leading to cancer
Date:8/18/2011

Washington, D.C. Cells with too few or too many chromosomes have long been known to be a hallmark of cancer but the cause of this abnormal number of chromosomes has been little understood. Now, in the August 19th issue of Science, researchers at the Georgetown Lombardi Comprehensive Cancer Center, a part of Georgetown University Medical Center, have identified a gene that is commonly mutated in human cancers and have demonstrated its direct role in causing aneuploidy, an abnormal number of chromosomes.

The researchers found that 20 percent of the brain cancer (glioblastoma multiforme), skin cancer (malignant melanoma), and bone cancer (Ewing's sarcoma) samples they examined made no STAG2 protein, often due to a missing or mutated STAG2 gene. The STAG2 gene encodes a component of a protein structure known as the "cohesin complex" which regulates the separation of replicated chromosomes during cell division.

What this means is that if the STAG2 gene has been inactivated by a mutation, chances increase that a cell undergoing division will distribute an uneven number of chromosomes to the two new "daughter" cells being created. These cells, which now have too few or too many genes, are significantly more likely to develop into cancer.

"Scientists have long been searching for the genetic basis of aneuploidy in cancer cells, and our study provides substantial new insight into that process," says the study's senior investigator, cancer geneticist Todd Waldman, M.D., Ph.D., an associate professor at Georgetown Lombardi.

"In the cancers we studied, mutations in STAG2 appear to be a first step in the transformation of a normal cell into a cancer cell," he says. "We are now looking at whether STAG2 might be mutated in breast, colon, lung, and other common human cancers."

The study may also provide a new direction for cancer therapy, says the study's lead author, David Solomon, Ph.D., a student in the M.D./Ph.D. pr
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Contact: Karen Mallet
km463@georgetown.edu
Georgetown University Medical Center
Source:Eurekalert

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