Research News

Analysis of Brain Tumors Defines Genetic Abnormalities

The most common form of malignant brain cancer in adults, glioblastoma multiforme (GBM), is not a single disease but appears to be four distinct molecular subtypes, according to a study by The Cancer Genome Atlas (TCGA) Research Network. The researchers involved in this study also found that response to aggressive chemotherapy and radiation differed by subtype. Patients with one subtype treated with this strategy appeared to succumb to their disease at a rate approximately 50 percent slower than patients treated with less aggressive therapy. This effect was seen to a lesser degree in two of the subtypes and not at all in the fourth subtype.

Although the findings do not affect current clinical practice, the researchers said the results may lead to more personalized approaches to treating groups of GBM patients based on their genomic alterations. The study, published in the journal Cancer Cell, provides a solid framework for investigation of targeted therapies that may improve the near uniformly fatal prognosis of this cancer. The research team for TCGA is a collaborative effort funded by the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI), both parts of the National Institutes of Health.

GBM is a very fast-growing type of tumor. In recent years, three of every 100,000 Americans have been diagnosed with GBM, representing the highest incidence rate among malignant brain tumors. Most patients with GBM die of the disease within approximately 14 months of diagnosis.

The TCGA researchers expanded on previous studies, which had established gene expression profiling as a means to identify distinct subgroups of GBM. “We discovered a bundle of events that unequivocally occur almost exclusively within a subtype,” said lead author D. Neil Hayes of the University of North Carolina at Chapel Hill. “These are critical events in the history of the tumor’s development and spread, and evidence is increasing that they may relate to the initial formation of the tumors.”

TCGA researchers reported that the nature of these events indicate that the underlying pathology of each subtype may begin from different types of cells. This may provide a better understanding of which cell types undergo changes that ultimately drive initial cancer formation. This finding has potential clinical significance since determining the types of cells that form GBM is critical for establishing effective treatment regimens. Because the response to aggressive chemotherapy and radiation differed by subtype, some classes of drugs would be expected to work for some tumor subtypes and not others.

The new findings build on TCGA’s detailed view of GBM genomic changes reported in the journal Nature in October 2008. TCGA, launched in 2006, is a comprehensive and coordinated effort to accelerate understanding of the molecular basis of cancer through the application of genome analysis technologies, including large-scale genome sequencing.

This work is detailed in a paper titled, “Integrated Genomic Analysis Identifies Clinically Relevant Subtypes of Glioblastoma Characterized by Abnormalities in PDGFRA, IDH1, EGFR, and NF1.” An abstract of this paper is available at the journal’s Web site.
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