Researchers say they have discovered a major reason why women who have a mutated version of the gene BRCA1 have such a high risk of breast cancer -- and that finding could lead to new treatments.
Scientists have known for more than a decade that women who have inherited certain mutations in the BRCA1 gene are at high risk for breast cancer. What they have not understood is exactly how a mutation in this gene leads to cancer.
The new study finds that a second gene, called PTEN, which acts as a brake on cancer, plays a key role.
BRCA1 normally repairs damage to other genes, such as PTEN. But when the gene had mutations, it doesn't repair any damage to PTEN. That then allows cancer cells to grow and divide, unchecked.
Dr. Ramon Parsons of Columbia University, who reports the work with colleagues on the website of Nature Genetics, says his team believes that is "probably a major way'' that defects in BRCA1 produce breast cancer.
Mutations in BRCA1 and its cousin, BRCA2, account for less than 15 per cent of all breast cancers, but women with mutations in these genes have a 50 to 85 per cent chance of developing breast cancer in their lifetime.
The cancers are generally aggressive and have a poor prognosis because they do not respond to usual drug therapies, such as Herceptin or tamoxifen.
Parsons' team made its findings about the connection between BRCA1 and PTEN after scanning 34 biopsies taken from women with BRCA1 mutations who had developed breast tumours.
They found that the PTEN gene had been split in two in many of the cases. The team believes that these types of large chromosomal mistakes stem directly from the tumour's faulty BRCA1.
In breast cancers from women with normal BRCA1, they rarely found large mutations in PTEN.
Parsons estimates that about 50 per cent of BRCA1 breast cancers will be found to have mutated PTEN once a complete analysis of chromosomal mutations is done. They also expect that other cancer genes, besides PTEN, are targeted by BRCA1.
"These findings are exciting because ever since the link was established between BRCA1 and breast cancer more than 10 years ago, we have been frustrated by our lack of understanding about how mutations in this gene cause breast cancer. We have been stymied by our limited resources to treat these cancers, which are associated with very poor prognoses," said Parsons in a statement.
"Now that we know that PTEN is involved, we finally have a target for therapy for these cancers."
