Since it's discovery in the early 1990's, scientists have identified hundreds of mutations in the BRCA1 gene, many of which are associated with an increased risk of cancer. Women with an abnormal BRCA1 or BRCA2 gene have up to a 60% risk of developing breast cancer by age 90. This year in the US alone, more than 20,000 women will be diagnosed with breast cancer resulting from mutations in either their BRCA1 or BRCA2 genes.

A functional BRCA1 gene is known to play a major role in preventing breast and ovarian cancer development - but just how it does this has long been debated. In the September 8th issue of Nature, researchers at the Salk Institute may have found an answer, and they hope their research may allow earlier detection and more effective treatments.

The researchers were working with mice that lacked the BRCA1 gene in their brains. In previous research the team had discovered that the neurons of these mice had a defect in the packaging of DNA. It turned out that BRCA1 was exerting regulatory control over a large number of genes by keeping these DNA bundled together tightly into a structure, known as heterochromatin, inside the nucleus. This tightly bundled DNA becomes inaccessible, and transcriptionally completely silent.

With BRCA1 absent, genes which are normally forced to be silent now become activated, "and they are able to do a lot of the things scientists ascribe to mutated BRCA1, which increases risk of cancer," says Salk research associate Gerald Pao, Ph.D., a study co-lead author. "Cells cannot efficiently repair their DNA, and there are problems with gene transcription and expression, errant cell division and chromosomal instability, among other things."

"From our findings, we propose that the role of BRCA1 in maintaining global heterochromatin integrity accounts for many of its tumor suppressor functions, and so when this crucial protein is missing, cancer can develop," Pao says.

Inder Verma, Ph.D., the study's senior investigator commented, "We hope this study now provides a new cohesive direction for BRCA1 research so that we can answer the fundamental questions about how this gene promotes cancer and how we might be able to improve early diagnosis and, possibly, treat BRCA1-induced cancer more effectively."

To learn more, please visit the official press release on the Salk Institute's website.