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Insight offers new angle of attack on variety of brain tumors
Date:12/15/2010

A newly published insight into the biology of many kinds of less-aggressive but still lethal brain tumors, or gliomas, opens up a wide array of possibilities for new therapies, according to scientists at Brown University and the University of California, San Francisco (UCSF). In paper published online Dec. 15 in the Journal of the National Cancer Institute, they describe how a genetic mutation leads to an abnormal metabolic process in the tumors that could be targeted by drug makers.

"What this tells you is that there are some forms of tumors with a fundamentally altered process," said Karl Kelsey, a professor of pathology and laboratory medicine and community health in the Warren Alpert Medical School of Brown and one of the paper's senior authors. "This is a really new way to look at potentially modifiable factors in brain tumors."

Scientists have known for a couple of years that a mutation in a gene called IDH is associated with glioma. They've also observed that people with gliomas carrying the mutation survive longer than those afflicted with tumors lacking the mutation. What the Brown and UCSF team show in the new paper is that the mutation is associated with a consistent pattern of an alteration known as "methylation" of the DNA which is associated with changes in gene expression. The pattern of methylation in tumors with the IDH mutation often occurred in metabolic genes, regardless of the tumor's specific type.

Margaret Wrensch, a professor of neurological surgery, epidemiology and biostatistics at UCSF's Helen Diller Family Comprehensive Cancer Center, said what the team found surprising is that DNA from almost all tumors with IDH mutations had the same distinctive methylation pattern. The degree of methylation throughout the genome was unusually high, and the same specific DNA was methylated.

"This one mutation is common to a whole subset of brain tumors," she said. "It's quite unique. It seems to dominate other
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Contact: David Orenstein
david_orenstein@brown.edu
401-863-1862
Brown University
Source:Eurekalert

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