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Key mutations act cooperatively to fuel aggressive brain tumor
Date:3/14/2011

Mutations in three pathways important for suppressing tumors cooperate to launch glioblastoma, an aggressive brain tumor that strikes children and adults. But new research from St. Jude Children's Research Hospital scientists shows those changes alone are not sufficient to cause cancer. Tumor formation requires additional mutations, some affecting different points in the same disrupted regulatory pathways.

Researchers demonstrated that in mouse models of glioblastoma, tumors develop in several regions of the brain.

The findings, as well as the technique investigators used to generate them, are now being used as a possible tool for understanding patients' responses to investigational therapies that target some of the same pathways. The research appears in the March 15 edition of the scientific journal Cancer Cell.

The work builds on previous studies that linked glioblastoma to disruptions in the RB1, p53 and Pten pathways, each of which has a key role in preventing tumor formation. For this study, St. Jude investigators developed a novel system that allowed them to delete the genes, either singly or in various combinations, for which the pathways are named. Researchers then tracked the impact of those deletions on the brains of adult mice.

Gliomas are the most common primary malignant brain tumor, representing more than half of the 18,000 malignant brain tumors diagnosed annually in the U.S. These tumors remain the second most common cause of cancer death among individuals ages 15 through 44. Survival is less than 10 percent for patients with the most aggressive gliomas subtype, glioblastoma.

"In this study, we set out to look at the contribution of each of these pathways and how they cooperate to generate gliomas," said Suzanne Baker, Ph.D., a member of the St. Jude Department of Developmental Neurobiology and the paper's senior author. "When you analyze a human tumor, you see all of the accumulated mutatio
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Contact: Summer Freeman
summer.freeman@stjude.org
901-595-3061
St. Jude Children's Research Hospital
Source:Eurekalert

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