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Insights into Common Brain Cancer

A researcher purifies DNA, which glows orange under UV light.Mike Mitchell.

A large-scale, comprehensive study of glioblastoma, the most common form of brain cancer, has uncovered new genetic mutations and other types of DNA alterations with potential implications for the disease's diagnosis and treatment.

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 it. Glioblastoma is the most common type of brain cancer in adults. It's a very fast-growing type of tumor, with most patients dying of the disease within about 14 months of diagnosis.

Like most cancers, glioblastoma arises from changes that accumulate in cells' DNA over the course of a person's life. Until recently, however, scientists have understood little about the precise nature of these DNA changes in glioblastoma and how they alter biological pathways to cause disease.

The new study involved members of The Cancer Genome Atlas (TCGA) Research Network, a collaborative effort funded by NIH's �����鶹��Ƶ Cancer Institute (NCI) and �����鶹��Ƶ Human Genome Research Institute (NHGRI). TCGA was launched in 2006 as a pilot program to determine the feasibility of a full-scale effort to systematically explore the universe of genomic changes involved in human cancer.

Ten different academic centers and over 125 investigators worked together, using several genome characterization technologies, to produce high-quality, multi-dimensional data for an unprecedented level of analysis. The researchers analyzed the genomes, or complete sets of DNA, of tumor samples donated by 206 patients with glioblastoma. TCGA's interim results were published on September 4, 2008, in the advance online edition of the journal Nature. A complementary study by Johns Hopkins researchers of 22 glioblastoma tumors, partly funded by NIH, was published on the same day in Science.

Among the TCGA network's findings were the identification of many gene mutations involved in glioblastoma, including 3 frequent but previously unrecognized mutations. By combining sequencing data with other types of genome characterization information, the team also delineated 3 core biological pathways that may play a role in glioblastoma. These are involved in the regulation of cell division; the response to DNA damage and cell death; and the regulation of growth factor signals. Each pathway was disrupted in more than three-quarters of the glioblastoma tumors.

“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 Dr. Elias A. Zerhouni. “Clearly, it is time to move ahead and apply the power of large-scale, genomic research to many other types of cancer.”