Columbia Researchers Pinpoint Fault in Breast Cancer Gene

In a study published October 28, 2011, in Science, researchers from the Institute for Cancer Genetics and Herbert Irving Comprehensive Cancer Center have finally pinpointed the flaw in BRCA1 that causes cancer.

“Since BRCA1 was first discovered in 1994, a major emphasis in hereditary breast cancer research has been to elucidate how BRCA1 mutations cause cancer,” says Thomas Ludwig, PhD, associate professor of clinical pathology and cell biology who led the study with Richard Baer, PhD, professor of pathology.

Women who have inherited a faulty BRCA1 gene are five times more likely to develop breast cancer in their lifetimes than women with normal BRCA1 genes.  Until now, scientists have thought the higher risk stems from mutations in a region of BRCA1 that acts as an enzyme.

But when Ludwig, Baer, and their colleagues generated mice with BRCA1 that had lost its enzymatic function while retaining its other functions, no tumors developed. Ludwig and his team then generated mice with a mutation that left BRCA1’s enzymatic function intact but destroyed its ability to interact with phosphoproteins, including Abraxas, Bach1, and CtIP. Tumors developed frequently in these mice.

The researchers’ next goal is to identify the phosphoprotein(s) that help BRCA1 suppress cancer, in the search for interventions to prevent breast cancer in women with BRCA1 mutations.