New breast cancer gene mutation discovered

By Dr. Ananya Mandal, MDApr 1 2012

Researchers have discovered a key to unlocking the genetic code behind a host of serious diseases after finding a new breast cancer gene mutation.

A large international study led by University of Melbourne researchers has identified a mutation linked to breast cancer attached to the newly identified gene, called XRCC2. Lead researcher Melissa Southey said the discovery, using high-speed technology, would hopefully mean that more gene mutations responsible for causing breast cancer could be rapidly identified in the next few years.

Initially, the XRCC2 mutation was found in two families by Prof Southey and a colleague based in The Netherlands. The discovery formed the basis for a much larger study to determine whether the mutation was more widely responsible for breast cancer, which proved correct. The DNA of 689 families with multiple members affected by breast cancer, and 1308 women who had early onset breast cancer, was then analyzed, as well as 1120 healthy people.

At present women with a history of breast cancer in their family can only be screened for two of the disease's known genetic mutations, Prof Southey said. The two genes account for about 20 per cent of breast cancer cases, she said, with the remaining 80 per cent not linked to any known mutations, she said. “At the moment, if a woman with a strong family history of breast cancer goes to clinical genetic services and undergoes testing for the genes that we know today, the most likely outcome is that she will not be found to have a mutation in any of those genes,” Prof Southey said. Prof Southey said the study, published today in the American Journal of Human Genetics, was continuing, with much more data to analyze.

“We really are very optimistic that we will find additional genes like this.” Prof Southey said researchers used the latest genetic sequencing technology, called massively parallel sequencing, in the discovery. Previously DNA sequencing using a method called Sanger sequencing could take weeks or months, she explained. By using the new method scientists could analyze a person's entire DNA in a few days, Prof Southey said.

One of the study's co-authors, Melbourne University's Dr Daniel Park, said the findings showed the technology could be used to discover other cancer-causing genes. “Our study approach could be applied to many other common, complex diseases with components of unexplained heritability, such as colorectal and prostate cancers,” he said.

“We believe further risk genes will be identified at a faster rate than before and potentially for other cancers such as colorectal and prostate cancers.”  Southey said the discovery of new genetic links would lead to more targeted treatments. “People whose breast cancer is associated with XRCC2 mutations could also benefit from specific treatments that target the genetic fault,” Prof Southey said.

Sean Tavtigian, one of the researchers, a Huntsman Cancer Institute (HCI) investigator and associate professor in the Department of Oncological Sciences at the University of Utah said, ““We have added to the list of genes that harbor mutations causing breast cancer… This knowledge will improve breast cancer diagnostics and add years to patients' lives. More important, relatives who have not been affected by the disease but carry the mutations will benefit even more. They can find out they are at risk before they have cancer and take action to reduce their risk or catch the cancer early.” Further research is underway. “A worldwide effort has already been launched to figure out what fraction of breast cancer is due to mutations in this gene and how high the risk conferred by these mutations actually is,” Tavtigian said.

XRCC2 may also provide a new target for chemotherapy. “A type of drug called a PARP inhibitor appears to kill tumor cells that have gene mutations in a particular DNA repair pathway. XRCC2 is in this pathway, as are BRCA1 and BRCA2. It's reasonably likely that a breast cancer patient who has a mutation in XRCC2 will respond well to treatment with PARP inhibitors,” said Tavtigian.

The University of Utah was the main collaborator on the research, which also involved other research institutes in Australia and France. Cancer Council SA chief executive Professor Brenda Wilson said the discovery had the potential to save lives by detecting risk earlier.