Breast Cancer Causing Gene, BRCA1 Mystery Solved

More than 20 years after scientists revealed that mutations in the BRCA1 gene predispose women to breast cancer, researchers at Yale have discovered the molecular mechanism that allows those mutations to cause breast cancer.

Understanding the molecular mechanism of the gene will not only help researchers design drugs to combat breast and ovarian cancer, but also help identify women who are at high risk of developing them, the authors say.

‘Understanding the mechanism of the BRCA-dependent DNA repair pathway will help scientists design drugs to kill cancer cells more efficiently.’

"There have been about 14,000 papers written about BRCA1, and you would think we already know everything about the gene, but we don't," said senior author Patrick Sung, professor of molecular biophysics and biochemistry and therapeutic radiology and member of the Yale Cancer Center.

The discovery of BRCA1's role in DNA repair and suppression of tumors was the first evidence that the risk of cancer could be inherited. It was originally thought that mutations in BRCA1 and the related BRCA2 gene might account for 7% to 8% of breast and ovarian cancers, Sung said. However, the cancer risk is likely a lot higher because in many cancer cases the expression of the BRCA genes is silenced even though no mutation can be found, he added.

Sung and colleagues reported that the interaction of BRCA1 with its partner BARD1 is necessary to recruit the exact genetic sequence needed to repair breaks in DNA caused by endogenous stress and environmental insults such as radiation exposure.

"Defining the mechanism of the BRCA-dependent DNA repair pathway will help scientists design drugs to kill cancer cells more efficiently," Sung said.

"Understanding this mechanism will provide the predictive power for doctors trying to establish a patient's risk of developing cancer."

The complete research report is published in the journal Nature.

Source: Eurekalert