Researchers have identified and described a network of mutated genes and gene processes that, together, contribute to fatal brain tumors.
 
Dr. Markus Bredel is the director of the Brain Tumor Institute Research Program at Northwestern University's Feinberg School of Medicine in Chicago and co-author of two related papers in the July 15 issue of the Journal of the American Medication Association.
 
He said, "There is not a single gene that accounts for the development of brain tumors. It's the concert of those genes and the interaction of those genes that ultimately determine the progression of cancer."
 
Bredel proposed that a combination of therapies targeting specific biological events might improve treatment outcomes for the development of glioblastomas, the deadliest type of brain tumor.
 
Currently people with glioblastomas now live an average of 12 to 14 months. "We hope that's the future of therapy -- that we can, over the long term, transfer this into a more chronic disease so patients could hopefully live 10 to 15 years," Bredel said. However he said development of a cure in that time frame is unlikely.
                                                                                                    
The researchers analyzed tissue from almost 200 tumors and identified the same pattern of mutations occurring in the same area or territories on 10 chromosomes. They found that by tracking these so-called "landscape genes," the researchers were able to predict how long the patients would live.

Bredel said up to 50% of the 30,000 to 40,000 genes in the human genome may be altered in glioblastoma and the key is discovering which changes are actually important.

"Many of those changes will be just passengers or bystanders," Bredel said. "We tried to count up and prioritize the genes that are potentially the most important in glioblastoma disease and as a means to develop future therapy."
 
The researchers started with a genome-wide approach, using tissue from 501 people with this type of tumor and worked their way to 31 genes that appear to be the leaders of the complex genetic changes leading to glioblastoma.
 
The study found these 31 genes were altered in up to 75% of glioblastomas, forming a landscape common to about three-quarters of all cases of glioblastoma. The researchers said within those 31 genes, a subset of seven genes allowed them to group the disease into low, intermediate and high risk in terms of outcome, a tool that may be useful for prognosis
 
The researchers found not only the genes were important, but the relationships between them were also critical.                                                                                                                                            
                   
In the second study, the researchers went deeper into the mechanisms driving two of the 31 genes, one so-called hub of genes and one gene that interacted with that hub, meaning those that have a high level of connectivity with the other genes.
                                                            
According to the study the hub gene is the EGFR (epidermal growth factor receptor) oncogene on chromosome 7 which is amplified in about 45% of glioblastoma cases. Oncogenes are genes that drive cancer growth.
 
The amplification seems to take place parallel with a decrease in function in another gene, ANXA7, located on chromosome 10. They said a decrease in the function of ANXA7 kicks the EGFR oncogene into overdrive, contributing to the development and progression of malicious glioblastomas.
 
"The authors have really made sense of these genetic changes and identified some of the pathways that seem to be crucial for glioblastoma development," said Dr. Boris Pasche, co-author of an accompanying editorial in the journal and associate director of the Comprehensive Cancer Center at the University of Alabama at Birmingham. "It's very exciting because it holds promise for identification of the Achilles' heel of this disease. If you can target several pathways that are implicated in a given disease, you can effectively change the course of the disease."