Mutated Suppressor Gene Leads to a Type of Breast Cancer

Mutated Suppressor Gene Leads to a Type of Breast Cancer
MONDAY, Dec. 10 (HealthDay News) -- Scientists believe they'vediscovered how mutations in the cancer-susceptibility gene called BRCA1can cause some breast cancers.
Basal-like breast cancers (BBCs) represent 10 percent to 20 percent ofall breast cancers. BBCs generally have a poor prognosis, are difficult totreat, and are almost always associated with hereditary mutations in theBRCA1 gene, the researchers said.
The researchers found that inherited mutations in the BRCA1 genedeactivate another gene known as PTEN, which helps to suppress tumors.This suppressor gene is deactivated by the mutated BRCA1 gene's failure torepair a break in the PTEN gene's DNA, the scientists said.
The loss of the PTEN gene's tumor-suppressing ability allows increasedcell activity that increases tumor growth. That action "can convert thecell from being a well-behaving entity to a bad citizen," said studyco-author Dr. Ramon Parsons, a professor of medicine and pathology atColumbia University's College of Physicians and Surgeons.
"This is a very important finding, because this type of breast cancerdoesn't have a type of therapy targeted at this point," Parsons said.Basal-like or triple negative tumors don't have receptors for the hormonesestrogen and progesterone or the protein HER2, which most breast cancertherapies target, he said. Drugs that can target the pathway related tomutated PTEN genes "may be a way we can improve the survival for womenwith these basal-like tumors," he added.
Parsons said several pharmaceutical companies already are developingdrugs to do just that.
"My guess is there's going to be a huge bolus of clinical trials withthese drugs in the next couple of years," he said. "Since there's going tobe such a large variety of compounds, my hunch is one or more will beeffective." By effective, Parson said he doesn't mean one of them willoffer a cure, but the drugs in the right combination could lead to acure.
The development of these drugs also may be important for other types ofcancers that can involve deactivating the PTEN gene, Parsons said.
The study results were published online Dec. 9 in the journal NatureGenetics.
Parsons said the discovery of the PTEN deactivation "was kind of a reallong-term detective story." For 10 years, researchers have been trying tounderstand how the mutation in the BRCA1 gene can cause breast cancer.Instead of using traditional gene-sequencing techniques, Parsons and hiscolleagues looked for physical breaks in the PTEN gene. "PTEN is actuallyphysically broken in half, we estimate, in 30 to more than 50 percent ofthe BRCA1 tumors," he said.
Dr. Jeffrey Weitzel, an associate professor of medical oncology at theCity of Hope Comprehensive Cancer Center in Duarte, Calif., said the studyby Parsons' team "helps us understand what's under-appreciated in thecomplex nature of tumor changes."
Andrew Godwin, director of the clinical molecular genetics laboratoryat the Fox Chase Cancer Center in Philadelphia, added: "As we move towardspersonalized health care [and] medicine, identifying the cadre of geneticdefects in a given breast tumor will likely influence how that patient isultimately treated."