Researchers ID Subset of Brain Cancers with Better Outcomes
May 1, 2010 - A national network of cancer researchers have identified a common set of molecular changes in some forms of the deadly brain tumor glioma that indicate a patient is likely to have a more favorable outcome.
The findings, published online April 15 in the journal Cancer Cell, may lead to more personalized approaches to treating glioma patients based on their individual genomic alterations. Participants included researchers at the Johns Hopkins Kimmel Cancer Center, University of Southern California and MD Anderson Cancer Center, and others participating in The Cancer Genome Atlas (TCGA) Research Network.
“The ability to differentiate brain tumors based on their altered genetic code lays the groundwork for more effective treatment strategies, such as targeted drug treatments,” says Stephen B. Baylin, M.D., professor of oncology and deputy director of the Johns Hopkins Kimmel Cancer Center.
For the study, TCGA researchers led by scientists Peter Laird, Ph.D., at University of Southern California and Kenneth Aldape, M.D. at MD Anderson Cancer Center, profiled genetic and epigenetic alterations in 273 glioblastomas, a highly lethal cancer that represents more than half of all glioma tumors.
Among this genome profiling data, the investigators found that a distinct subset of glioblastomas had heavy areas of methylation - a process in which biochemicals called methyl groups are added to certain DNA sequences known as CpG islands. The scientists say that tumors in which this “chemical flagging” or methylation is found in large numbers of genes might suggest a separate subgroup of gliomas.
Indeed, the researchers found that 24 of the 273 glioblastoma samples (8.8 percent) met the characteristics of this new subtype. They had distinct molecular features, including a high frequency of mutations to the gene isocitrate dehydrogenase 1 (IDH1), a mutation previously linked by another group of Johns Hopkins scientists to brain cancer and better survival. Patients with methylated tumors were found to be younger at diagnosis (average ages of 36 versus 61), displayed improved survival times (average survival of 150 weeks versus 42 weeks), and were twice as common among low- and intermediate-grade gliomas.
The researchers said “molecular characterization using markers such as methylation is the only way to identify in patients with advanced brain tumors whose tumors are more or less likely to respond well to treatment.”
"Such findings are critical to the detection and treatment of brain cancer based on the genetic or epigenetic profile of each patient's disease," says National Institutes of Health (NIH) Director Francis Collins, M.D., Ph.D. "The depth and breadth of expertise in The Cancer Genome Atlas research network, combined with ever-improving genomic technologies, is generating remarkably detailed insights into cancer."
TCGA is a collaborative effort of more than 150 researchers at dozens of institutions across the nation funded by the National Cancer Institute and National Human Genome Research Institute. In ongoing TCGA research projects, investigators hope to identify genetic and epigenetic alterations in ovarian, lung and colon and other cancers, Baylin said.
The current study was supported by the National Cancer Institute and grants from the Brain Tumor Funders’ Collaborative, the V Foundation and the Rose Foundation.
Glioblastoma is a very fast-growing type of tumor. In recent years, three of every 100,000 Americans have been diagnosed with the cancer, representing the highest incidence rate among malignant brain tumors, according to the National Cancer Institute. Most patients with glioblastoma die of the disease within approximately 14 months of diagnosis.
Leslie M. Cope and James G. Herman of Johns Hopkins also were authors of the study. Other institutions contributing to the work were: the University of Southern California; the University of Texas MD Anderson Cancer Center; Genentech, Inc.; Massachusetts Institute of Technology and Harvard University; Dana-Farber Cancer Institute; University of North Carolina at Chapel Hill; Washington University School of Medicine; and the University of California, Berkeley.
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