More than 10 years ago, scientists discovered that mutations in a gene called BRCA1 lead to a particularly deadly type of breast cancer. Now an international group of researchers has found at least one reason why. BRCA1 inactivates a tumor suppressor gene known as PTEN.
Mutations occur spontaneously, but most organisms have mechanisms that can prevent the damage they might cause. PTEN has instructions to produce a protein that stops the uncontrolled cell growth of cancer. BRCA1, the scientists reported online Sunday in Nature Genetics, prevents PTEN from doing its work.
The researchers found that inactivating the PTEN gene in mice led to the formation of the malignant tumor associated with BRCA1 mutations. Then they examined PTEN in nonhereditary breast tumors from 297 patients and tumors from 34 women who had inherited the BRCA1 mutation. In most cases, the protein that PTEN produces was undetectable in tumor cells, but clearly present in nearby normal cells.
PTEN might be a target for chemotherapy. “I am cautiously optimistic,” said Dr. Ramon E. Parsons, the lead researcher and a professor of pathology at Columbia, “that within the next five years we’ll be using drugs that are effective on the PTEN pathway.”
Women with BRCA1 mutations are at very high risk for breast cancer at an early age. Those who know they carry the mutation sometimes choose preventive mastectomies.