The Cancer Genome Atlas (TCGA) Research Network, a collaborative effort funded by the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI) of the National Institutes of Health (NIH), has reported the first results of its large-scale, comprehensive study of the most common form of brain cancer, glioblastoma (GBM). In a paper published Sept. 4, 2008, in the advance online edition of the journal Nature, the TCGA team describes the discovery of new genetic mutations and other types of DNA alterations with potential implications for the diagnosis and treatment of GBM.

Among the TCGA findings are the identification of many gene mutations involved in GBM, including three previously unrecognized mutations that occur with significant frequency; and the delineation of core pathways disrupted in this type of brain cancer. Among the most exciting results is an unexpected observation that points to a potential mechanism of resistance to a common chemotherapy drug used for brain cancer.

More than 21,000 new cases of brain cancer are predicted in the United States this year, with more than 13,000 people likely to die from the disease. GBM, which is the type of brain cancer most often found in adults, is a very fast-growing type of tumor. Most patients with GBM die of the disease within approximately 14 months of diagnosis.
The TCGA network analyzed the complete sets of DNA, or genomes, of tumor samples donated by 206 patients with GBM. The work complements and expands upon a parallel study by Johns Hopkins researchers of 22 GBM tumors, which was also published today in the journal Science.

"These impressive results from TCGA provide the most comprehensive view to date of the complicated genomic landscape of this deadly cancer. The more we learn about the molecular basis of glioblastoma, the more swiftly we can develop better ways of helping patients with this terrible disease,"said NIH Director Elias A. Zerhouni, M.D. "Clearly, it is time to move ahead and apply the power of large-scale, genomic research to many other types of cancer."

Like most cancers, GBM arises from changes that accumulate in cells' DNA over the course of a person's life - changes that may eventually lead to the cells' uncontrolled growth. However, until recently, scientists have understood little about the precise nature of these DNA changes and their impact on key biological pathways that are important to the development of new interventions.

The NCI and the NHGRI initiated TCGA in 2006 to accelerate understanding of the molecular basis of cancer through the application of current genome characterization technologies, including large-scale genome sequencing. TCGA was launched as a pilot program to determine the feasibility of a full-scale effort to potentially systematically explore the universe of genomic changes involved in all types of human cancer.

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