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New study reveals for first time how BRCA1 mutations cause breast cancer
Date:12/9/2007

Breast cancer tumors caused by BRCA1 are known as basal-like or triple-negative because these tumors usually lack estrogen, progesterone, and HER2 receptors, which are needed for most breast cancer treatments to be effective. Basal-like breast tumors are found in 10 to 20 percent of women with non-hereditary breast cancer (meaning, not caused by a genetic mutation in BRCA1 or another gene), and the researchers found that PTEN is also lost in the majority of these breast tumors as well.

Our results point to PTEN as a major player in both hereditary and non-hereditary basal-like breast cancer, a finding that may now be exploited to develop new therapeutic strategies to improve outcomes for women with these aggressive tumors, said Dr. Saal, who at the time of the research, was a fellow in Dr. Parsons Avon Foundation Breast Cancer Research Laboratory.

The researchers also predict that other cancer genes besides PTEN are targeted by BRCA1. By using the same techniques we used to find gross chromosomal rearrangements in PTEN, we hope to start identifying additional mutated genes involved in the development of breast cancer, said Dr. Parsons.

These kinds of mutations that break tumor suppressors in half may turn out to be common in many kinds of carcinomas, particularly those with deficiencies in DNA repair pathways similar to BRCA1, a question that only a systematic search can answer, said Dr. Saal.

Similar research is underway in tumors from carriers of germline mutations in BRCA2, the other known major breast cancer susceptibility gene, said Dr. Borg. BRCA2 has a role downstream in the same DNA double strand break repair pathway as BRCA1, but tumors from BRCA2 mutation carriers have a quite different phenotype compared to BRCA1 tumors, less often involving PTEN loss. However, like BRCA1, BRCA2 tumors have an instable genome with massive chromosomal aberrations, suggesting that other genes may be targeted.

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Contact: Elizabeth Streich
eas2125@columbia.edu
212-305-6535
Columbia University Medical Center
Source:Eurekalert

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