The Cancer Genome Atlas (TCGA) Research Network—a nationwide collaboration to study the molecular basis of cancer—announced results of its first study of the most common form of brain cancer, gliblastoma (GBM). Peter Laird, associate professor of surgery, biochemistry and molecular biology at the Keck School of Medicine of USC and director of the USC Epigenome Center, was one of a national consortium of scientists who took part in the large-scale study, which appeared in the September edition of the journal Nature. The article 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.

“We are excited to be part of this large-scale collaboration aimed at understanding the genetic and epigenetic characteristics underlying this deadly disease,” Laird said.

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. Epigenetic (DNA methylation) analyses were performed collaboratively by the USC Epigenome Center and The Johns Hopkins University, Laird said.

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 National Cancer Institute (NCI) and the National Human Genome Research Institute of the National Institutes of Health 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.

In its Nature paper, the TCGA Research Network describes the interim results of its analyses of GBM, the first type of cancer to be studied in the TCGA pilot. The pioneering work pulled together and integrated multiple types of data generated by several genome characterization technologies from investigators at 18 different participating institutions and organizations. The data include small changes in DNA sequence, known as genetic mutations; larger-scale changes in chromosomes, known as copy number variations and chromosomal translocations; the levels of protein-coding RNA being produced by genes, known as gene expression; patterns of how certain molecules, such as methyl groups, interact with DNA, known as epigenomics; and information related to patients’ clinical treatment.

”This type of comprehensive, coordinated analysis of unprecedented multi-dimensional data is made possible by advanced technologies utilized by teams of scientists driven to solve complex questions,” said NCI Director John E. Niederhuber, M.D. “It will now fall to a dedicated cadre of laboratory scientists to turn this important information into new life-saving therapies and diagnostics for cancer.

For more details about The Cancer Genome Atlas, including Q&As, a graphic, a glossary and a brief guide to genomics, visit the Cancer Genome Atlas Web site.