Scientists identify gene linked to many breast cancers

Women who inherit mutated forms of those genes are at increased risk of developing breast cancer earlier in life.

In this case women are born with a healthy version of the new gene, dubbed IKBKE, but a mutation occurs during life that causes it to churn out too many copies of itself in breast cells, but nowhere else in her body.

The new breast cancer gene "plays a crucial role in the formation and survival of tumours," Hahn said.

The discovery was to be published today in the journal Cell.

An estimated 22,300 women in Canada will be diagnosed with breast cancer this year, and 5,300 will die of it.

An internationally recognized Canadian breast cancer expert says IKBKE has many of the hallmarks of a gene that could become important in cancer.

"It's present in a lot of (breast) cancers. If it was only found in one per cent of cancers, that would mean potentially only one per cent of the women could benefit from a drug," says Dr. Steven Narod, a University of Toronto professor and co-author of the original paper that identified the BRCA1 gene.

"If there's a 10-per-cent chance that this leads to a treatment for breast cancers that's going to be effective for 30 per cent of women, in our way of measuring things that's a big advance."

And there's reason to be hopeful. Herceptin, considered the largest breakthrough for breast cancer in the past 15 years, and Gleevec, a drug that has revolutionized the treatment of leukemia and some gastrointestinal tumours, also work by shutting down a single mutant gene.

While many genes are mutated, only a small fraction are probably important for cancer, Hahn says.

The rest are ‘passenger' mutations, which exist in tumours but have no functional consequences.

Old gene-sorting methods didn't allow researchers to distinguish between the two. Scientists had to evaluate genes one at a time. The technology now exists for experiments to be done on hundreds if not thousands of genes at once.

"My lab started out with the question, how can we come up with a very efficient way of figuring out, of all of these mutations, which are the ones that are really important for driving cancer?" Hahn says.

They focused on a class of proteins called kinases, which act as molecular starter pistols for chemical reactions within cells. "We asked the question: ‘If we put in too much of any individual kinase, will it help turn a cell into a cancer cell in the lab?' "

After scouring through some 1,200 genes, they found five could do just that.

At the same time, they took cancer cells from patients and turned off the same set of genes, looking for those crucial for the cells to survive.

What they found was a small set of genes not only essential for cancer cells to survive but — when over-produced — drive cancer formation.

And only one —IKBKE — jumped out as the one that was mutated in a significant proportion of human breast tumours.

In experiments, when IKBKE was "silenced" or switched off, the cancer cells died.

The goal now is to develop a drug that does that in women. Kinases are a class of molecules that chemists know well how to target. Three new drugs in cancer, Gleevec and the lung-cancer drugs Tarceva and Arissa, are all kinase inhibitors, or so-called "smart bombs." The drugs have fewer side effects than chemotherapy and are given orally in pills.

Herceptin targets a molecule called HER-2, which is produced in 20 to 25 per cent of breast cancers. "So this is on the order of magnitude of HER-2, which clearly has been shown to benefit patients when targeted with Herceptin," Hahn says.

However, Dr. Stephen Chia, a medical oncologist with the B.C. Cancer Agency in Vancouver, says bigger studies are needed to validate the findings.

"It's definitely not something that as a clinician I can utilize today," Chia says. But no one knows why most breast cancers develop, he says. They're not genetic. "They might have identified a very common sporadic mutation in breast cancer."

source : www.canada.com