Scientists discover how BRCA1 gene causes cancer

Scientists discover how BRCA1 gene causes cancer
An illustration released by New York's Columbia University Medical Center on December 9, 20007. Mutations in the BRCA1 breast cancer gene appear to be linked with the loss of a protein important for putting the brakes on cell growth, a finding that could lead to new therapies, researchers said on Sunday. (Handout/Reuters)CHICAGO (Reuters) - Mutations in the BRCA1 breast cancergene appear to be linked with the loss of a protein importantfor putting the brakes on cell growth, a finding that couldlead to new therapies, researchers said on Sunday.
The breakthrough could lead to more effective therapies forwomen with an aggressive and especially deadly cancer known astriple-negative that does not respond to current advanceddrugs, the researchers said.
"It doesn't have a good target for therapy at this point,"said Dr. Ramon Parsons of Columbia University Medical Center inNew York, who worked on the study.
Scientists have known for more than a decade that womenwith certain alterations in the BRCA1 gene were at high riskfor breast cancer. What they have not understood is exactly howa mutation in this gene leads to cancer.
Researchers at Columbia, working with at team at Sweden'sLund University, now believe mutations in the BRCA1 gene canleave cells incapable of repairing routine DNA damage. Whensuch damage occurs in a protein called PTEN, which regulatesthe growth of cells, cell growth is unchecked and tumors form.
Women with faulty copies of BRCA1 or BRCA2 have a 50 to 85percent chance of getting breast cancer. Mutations in thesegenes account for 5 to 10 percent of breast cancer cases.
Most breast tumors are called estrogen-receptor positive,because they are fuelled by the hormone estrogen. About 20percent are HER2-positive, because a protein called HER2 isinvolved. A third type is driven by the hormone progesterone.
These types of cancer have good treatments.
Then there are basal-like or triple-negative tumors, sonamed because they lack estrogen, progesterone or HER2receptors needed for most breast cancer drugs to work.
UNCHECKED GROWTH
"The basic idea is that BRCA1 is a repair enzyme that isinvolved in coordinating the repair of double strand DNAbreaks," said Parsons said in a telephone interview.
"When it is mutated, it is no longer present in a cell. Ifa cut occurs in PTEN, there is no way for this cell to fix it,"said Parsons, whose study was published in Nature Genetics.
"It is like cutting the brake cable on a car," he said. "IfPTEN is broken, you turn on a pathway that tells the cell togrow. It tells the cell to start dividing. It tells the cell,'don't die."'
Parsons said loss of the protein PTEN is how breast cancergets started in women who have inherited the BRCA1 genemutation.
His team made the connection between BRCA1 and PTEN bysearching for chromosome breaks within the PTEN gene.
They scanned 34 biopsies taken from women with BRCA1tumors. The PTEN gene had been split in two, but inadequatelyrepaired in about one-third of the cancers. In some cases,entire sections of the gene were missing.
They said these chromosomal mistakes trace back to thetumor's lack of BRCA1, which is charged with cell repair. Heestimates that about 50 percent of BRCA1 breast cancers harbormutated PTEN.
"These tumors have very high frequency loss of the PTENprotein," Parsons said. In breast cancers from women withnormal BRCA1, they rarely found large mutations in PTEN."A lot of drug companies are working on this. There isreasonably good hope that this approach will improve therapyfor patients," Parsons said.Basal-like breast tumors are also found in 10 to 20 percentof women whose cancer was not caused by BRCA1 or another gene.The researchers found PTEN is lost in most of these breasttumors as well.(Editing by Jackie Frank)