August 27, 2012
Genomic Variant Increases Risk Of Some Brain Tumors
Brett Smith for redOrbit.com - Your Universe Online
Of the 6.4 billion nucleotides in the human genome, a single change from adenine to guanine at a specific location recently identified by geneticists can increase the odds of certain kinds of brain tumors by six times, according to the scientists´ report in the latest edition of the journal Nature Genetics.
The results produced by researchers at the University of California at San Francisco (UCSF) and the Mayo Clinic could result in the identification and preventative treatment of some types of gliomas in at-risk individuals.
"Being able to tell people that the mass in their brain is this type of tumor is actually good news, because it has a much better prognosis than other brain tumors," said senior author Dr. Robert Jenkins, a pathologist at the Mayo Clinic Cancer Center. "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."
A few years ago researchers began the hunt for a genetic mechanism that could lead to glioma development. They located a portion on chromosome 8 that contained several single nucleotide polymorphisms, or "SNPs," that were possible candidates. Jenkins and his colleagues then used “next generation sequencing” and genetic tagging to single out the SNPs that were causing brain tumors to form.
The results of their labor-intensive sequencing yielded seven candidates, including the SNP called rs55705857, which confers a relatively higher risk for glioma development. The amount of work into finding these regions highlights the value of actual genetic sequencing, versus the use of mathematical and computational models, the authors said.
The researchers are now looking to more positively confirm the carcinogenic effect of this SNP, but Jenkins assured that if it´s not “it´s pretty close.”
If the targeting of the joint research team is slightly off, the years of genetic sequencing have not been in vain as the work will eventually lead to more refined identification and treatment techniques.
"Understanding how this variant causes people to get these less aggressive, but still lethal, tumors will be extremely important," said co-author Margaret Wrensch, a professor in the Department of Neurological Surgery at UCSF. "It may eventually lead to methods to reverse the course of these tumors or possibly to prevent their formation."
Computer models used in the research indicated that the region may be a microRNA, a special class of nucleic acid that manages the activity of genetic signaling within cells. The modeling places the candidate SNP within the functional part of the microRNA, suggesting that an alteration in genetic code from adenine to guanine could have considerable consequences. Future research will also focus on determining if the microRNA actually exists, and what its function might be.
"The altered microRNA might target tumor 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," Jenkins said. "One of the big challenges of the current genomic era is to assign functions to all these new gene variants."