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Gene variant that ups risk of brain tumours discovered

London , Mon, 27 Aug 2012 ANI

London, August 27 (ANI): People who carry a "G" instead of an "A" at a specific spot in their genetic code have roughly a six-fold higher risk of developing certain types of brain tumours, a new study has found.

The findings could help researchers identify people at risk of developing certain subtypes of gliomas which account for about 20 percent of new brain cancers diagnosed annually in the U.S. and may lead to better surveillance, diagnosis and treatment.

Researchers still have to confirm whether the spot is the source of tumours, but if it's not, "it is pretty close," said senior author Robert Jenkins, M.D., Ph.D., a pathologist at the Mayo Clinic Cancer Center.

"Based on our findings, we are already starting to think about clinical tests that can tell patients with abnormal brain scans what kind of tumour they have, just by testing their blood," Jenkins stated.

A few years ago, researchers began hunting for regions of the genome that might be associated with the development of gliomas. These groups observed a portion of chromosome 8 that contained single nucleotide polymorphisms or "SNPs" associated with brain tumours.

Since then, Dr. Jenkins and Margaret Wrensch, Ph.D., professor of neurological surgery at the University of California, San Francisco, have been using a combination of sophisticated genomic techniques to search for the SNP causing brain tumours to form.

They honed in on seven candidates. One-the SNP called rs55705857 -- confers a relative risk approaching that is seen with BRCA1, the breast cancer gene. Interestingly, this region was only found through the most laborious method used by the researchers, next generation sequencing, suggesting that experimental and mathematical shortcuts may miss such rare, highly potent gene variants, Dr. Jenkins said.

Drs. Jenkins and Wrensch found that having the "G" guanine version of this SNP-rather than the more common "A" adenine version-was strongly associated with slower growing gliomas.

"Being able to tell people that the mass in their brain is this type of tumour is actually good news, because it has a much better prognosis than other brain tumours," Dr. Jenkins explained.

"So what is it that predisposes people to develop less aggressive, but still lethal, gliomas? That makes understanding the function of this variant even more important," he said.

As part of their work, the researchers compared the sequence of the gene variant throughout mammalian evolution and found that it has been conserved as far back as the platypus. Computer modeling indicated that the region may be a microRNA, a special kind of nucleic acid that controls the activity of genetic messages within cells.

The modeling places the SNP within the functional part of the microRNA, suggesting that a change in genetic code from an A to a G could have significant consequences. The research team is investigating whether the microRNA actually exists, and what its functional implications might be.

"The altered microRNA might target tumour suppressor genes, it might activate a cancer gene, it might be involved in regulating the stability of the genome, or there might be something else going on altogether. One of the big challenges of the current genomic era is to assign functions to all these new gene variants," Dr. Jenkins added.

The findings have been published online in the journal Nature Genetics. (ANI)


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