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International study points to new breast cancer-susceptibility gene

BOSTON -- A gene whose existence was detected only a couple of years ago may increase womens risk of breast cancer when inherited in a mutated form, and may contribute to prostate cancer as well, researchers at Dana-Farber Cancer Institute and colleagues in Finland report in a new study.

The gene, known as PALB2, may play a role in only about 1 percent of breast cancer cases in the select population that was studied (Finnish women), but its discovery sheds light on the complex web of gene interactions that underlies the disease, say the authors of the study, which is being published by the journal Nature on its Web site, www.nature.com/nature, and later in a print edition.

"Breast cancer can arise from a wide variety of genetic abnormalities, and mutations acquired during the evolution of breast tumor cells are relatively common in the disease," said the studys co-lead author, Bing Xia, PhD, of Dana-Farber. "However, only about 10 percent of all cases are the result of inherited mutations, and, of those, only about 20-30 percent result from mutations in the two main breast cancer-susceptibility genes, BRCA1 and BRCA2. So there is room for other such genes to be discovered."

The new study stems from research by Xia and Dana-Farber's David Livingston, MD, a senior author of the paper, into BRCA2's "binding partners" proteins that interact with the BRCA2 protein. They found that the PALB2 protein is an especially close partner of BRCA2, with substantial portions of the proteins binding to each other.

"We found that PALB2 helps anchor BRCA2 in key areas of the cell nucleus, where BRCA2 repairs damaged DNA," Xia said. Mutations in BRCA2 can prevent such repairs from being made, which can lead to runaway cell growth. If BRCA2 is normal, but PALB2 is defective, BRCA2 may be out of position for fixing damaged DNA, with similar pathological effects on cell growth.

To determine wh
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Contact: Bill Schaller
william_schaller@dfci.harvard.edu
617-632-5357
Dana-Farber Cancer Institute
8-Feb-2007


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