Genetic Fusion in Brain Cancer Discovered

Glioblastoma causes include a fusion of two genes

(RxWiki News) Glioblastoma is the most common and unfortunately the most aggressive brain cancer. A recent study has pinpointed a genetic fusion that helps these brain tumors develop.

This discovery could translate into new treatment possibilities.

A small percentage of glioblastomas is caused by a fusion of two genes. Targeting the proteins produced by this abnormal gene fusion slowed down the growth of tumors when induced in mice.

"Learn the exact type and nature of cancer you have."

These are the findings of researchers at Columbia University Medical Center (CUMC) in New York.

“From a clinical perspective, we have identified a druggable target for a brain cancer with a particularly dismal outcome. From a basic research perspective, we have found the first example of a tumor-initiating mutation that directly affects how cells divide, causing chromosomal instability," said study leader Antonio Lavarone, MD, professor of pathology and neurology at CUMC.

"This discovery has implications for the understanding of glioblastoma as well as others types of solid tumors,” said Dr. Lavarone, a member of the Herbert Irving Comprehensive Cancer Center at New York-Presbyterian Hospital/Columbia University Medical Center.

It's estimated that about 10,000 Americans are diagnosed with glioblastomas every year and, at this point, no treatment works to save lives. So understanding its origins is important for developing new treatments.

For this very small study, researchers looked for gene fusions by analyzing the genetic makeup of glioblastomas from nine patients.

They found in the tumors that two genes fuse together - FGFR (fibroblast growth factor receptor) and TACC (transforming acidic coiled-coil). This fusion was linked to the development of glioblastomas.

Investigators saw aggressive tumors formed in 90 percent of the animals when FGFR-TACC was injected into brain cells of healthy mice.  

Researchers also looked to see the effect of a drug that blocks an enzyme which enables the fusion to go about its deadly business. They found the drug prevented mitosis (cell division) and doubled the lifespan of the mice, compared to mice that didn't receive the drug.

dailyRx asked Cedars-Sinai neurosurgeon, Keith L. Black, MD, for his thoughts on this research. "Clearly important is the finding that the fusion of two genes – FGFR and TACC – causes genetic instability that is a hallmark of cancer," said Dr. Black who is chair and professor of Cedars-Sinai’s Department of Neurosurgery and director of the Cochran Brain Tumor Center.

"But other questions remain: Do other fusions also occur in brain cancer? If so, how many? And will targeting the proteins resulting from these fusions bring clinical benefits to patients? If the fusion proteins that cause genetic instability are an early event in the formation of cancer, blocking them would be a logical step," said Dr. Black, who is also director of the Maxine Dunitz Neurosurgical Institute and the Ruth and Lawrence Harvey Chair in Neuroscience.

"But if many other cancer proteins also have been turned on by the time the tumor is detected, blocking the early fusion proteins may have limited clinical effect. The train may have already left the station, so to speak. That notwithstanding, this observation is a step forward," concluded Dr. Black.

This research was published July 26 in the journal Science.

This research was supported by National Cancer Institute grants, National Library of Medicine, National Institute of Neurological Disorders and Stroke, Partnership for Cure, Chemotherapy Foundation, the Associazione Italiana per la Ricerca sul Cancro, and the Italian Ministry of Health.

Several of the authors and CUMC have filed a patent application related to the diagnostic and therapeutic use of FGFR-TACC gene fusions. Otherwise, the authors declare no financial conflicts of interest.

Review Date: 
July 26, 2012