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Brain Cancer Health Center

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Genetic Defect at Work in Deadly Brain Tumors

1 in 4 Glioblastomas May Have Newly Discovered Fault in Gene
WebMD Health News
Reviewed by Laura J. Martin, MD

Dec. 22, 2010 -- Scientists say they’ve discovered a genetic defect that may contribute to the development of as many as one in four cases of glioblastoma, the most common and aggressive type of brain tumor.

The defect, a deletion in a gene known as NFKBIA, prevents cells from making enough of a protein that acts as a natural tumor suppressor.

Without the protein, called I-kappa-B, cancer cells become particularly aggressive and difficult to kill.

The study, which was published online Wednesday in The New England Journal of Medicine, found that patients with the NFKBIA deletion had significantly worse responses to treatment and much shorter survival times than those whose tumors did not have the defect.

When researchers boosted levels of I-kappa-B in cancer cells, however, the cells became more sensitive to a chemotherapy drug, giving researchers hope that they’d found a kind of biochemical Achilles’ heel for this kind of tumor, which is nearly always fatal.

“Unfortunately, glioblastoma is one of the most aggressive of human tumors, the median survival for patients with glioblastoma has not changed substantially since we started radiation many years ago, so there’s an urgent need to find therapies that prolong outcomes in these patients,” says Kenneth D. Aldape, MD, professor of pathology at the University of Texas M.D. Anderson Cancer Center in Houston, who was a co-author on the study.

“This provides the first step for a targeted therapy for a subset of patients with glioblastoma,” he says.

2 Gene Defects Show Up in a Majority of Brain Tumors

For the study, researchers tested 790 human glioblastoma brain tumors for defects in the NFKBIA gene and for abnormalities in a related, previously known gene that codes for epidermal growth factor receptor, or EGFR.

Researchers found that about one in four tumors carried the NFKBIA deletion. The EGFR glitch was present, as other studies had found, in about one-third of these tumors.

Only about 5% of all tumors carried both defects, indicating that the two genes, which affect the same biochemical pathway, may be responsible for about 60% of these kinds of brain tumors.

“In the majority of the cases, one of these two genes or abnormalities in these genes contributes significantly to the malignant behavior of these cells,” says senior author Griffith Harsh, MD, professor of neurosurgery at the Stanford University School of Medicine.

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