Gene fusion signposts aggressive brain cancer

Glioblastoma is one of the most common and aggressive forms of brain cancer, and the Columbia University Medical Center's (CUMC) discovery that a subset of cases are caused by the fusion of two genes could open the door to better diagnosis and more tailored treatment, if only for a tiny group of patients.

Glioblastomas affect up to 10,000 people in the U.S. each year, and despite surgery and radio- and chemotherapy, patient survival is generally measured in months rather than years. In the study published in Science, the researchers found a fusion of two genes, FGFR (fibroblast growth factor receptor) and TACC (transforming acidic coiled-coil), in 9 patients with glioblastoma.

The researchers then screened 97 tumor samples from the Cancer Genome Atlas project, sponsored by the National Cancer Institute, and found the same fusion in three cases. The fused genes produce a mutant protein (known as a fusion protein), and study leader Antonio Iavarone, professor of pathology and neurology at CUMC, described the tumors as being "addicted" to this protein, which leads to problems with cell division and abnormalities in the chromosomes in the tumor cells. This is known as aneuploidy, and is a hallmark of cancer.

"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. This discovery has implications for the understanding of glioblastoma as well as others types of solid tumors," Iavarone added.

The fusion protein caused brain tumors in mice, and then dosing them with an experimental drug that targeted FGFR kinase meant that the cancers in these mice grew more slowly, and the mice lived longer. FGFR kinases are currently in development for the treatment of a number of types of cancer.

Glioblastomas are likely to be caused by a number of different causes, and this approach, which is still at a very early stage, is unlikely to help all patients. Commenting on the finding, Cancer Research UK's Laura Bell said to the Press Association that the study could be the first vital step to a treatment for people with few other options. Knowing this genetic marker--and discovering others--could lead to closely tailored and personalized therapy for patients, improving the outcome for this aggressive disease that has affected many over the years, including Sen. Edward Kennedy in 2009 and New York Mets all-star catcher Gary Carter this year.

- read the press release
- see the abstract
- check out the article from the Press Association
- see the article in New Scientist

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