Scientists discover "missing link" between rare disease and inherited forms of breast cancer

New pathway to BRCA1 discovered

Boston - Scientists following the gene trail of one of the world's rarest diseases have found it leads to an entirely unexpected place - to BRCA1, a gene that, when defective, is the most common source of inherited breast cancer.

In two studies published in the February issue of Molecular Cell, researchers led by Alan D'Andrea, M.D., of Dana-Farber Cancer Institute show how genes involved in a condition called Fanconi anemia form a "pathway" to the activation of BRCA1. If BRCA1 or any of the Fanconi genes are abnormal, the risk of cancer increases dramatically.

"There's strong evidence that under normal conditions, BRCA1 helps repair DNA damage in cells, preventing the cells from becoming cancerous," D'Andrea says. "But until now, little was known of how BRCA1 is switched on. This new study presents a pathway leading to BRCA1 activation - and it was discovered by studying a condition that's known to affect only 500 families in the United States."

The finding means that physicians may soon have a new tool for determining who is at risk for inherited breast cancer. Since a mutation in any of the Fanconi genes can block BRCA1 from being activated - thereby preventing it from doing its DNA repair work - testing for those mutations may offer a way of identifying women likely to develop breast tumors.

Although inherited forms of breast cancer comprise only about 5 percent of all breast cancer cases, testing for mutations in Fanconi genes could help identify women with normal BRCA1 genes who are still at risk for the disease.

The new study is an outgrowth of D'Andrea's research into Fanconi anemia, an inherited disorder that causes children to develop bone marrow failure by age five, leaving them unable to produce oxygen-carrying red blood cells. While a bone marrow transplant can cure the failure, many patients go on to develop cancer as young adults - usually leukemia, but also tu

Contact: Todd Ringler
Dana-Farber Cancer Institute

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