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Mysteries of a Common Brain Cancer Revealed

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A study published in Science by Johns Hopkins researchers reveals a "comprehensive map" of genetic mutations that occur in the second most common form of brain cancer, oligodendroglioma, according to a university press release. The team sequenced protein-coding genes in seven tissue samples of the brain cancer, and found recurring mutations in two genes — CIC and FUBP1 — that had never before been associated with this type of cancer. These two genes regulate cell-signaling processes, and CIC mutations have been linked to other cancers, the press release says. The team found mutations in the two genes in an additional 27 oligodendroglioma samples, and says the mutations may explain the "two hit" theory of how this cancer forms. "In oligodendrogliomas, the 'first hit' has long been known to occur in regions of chromosome 1 and 19, which fuse together resulting in a loss of a large number of genes on both chromosomes 1 and 19," the press release says. "Up to 70 percent of oligodendroglioma patients have these DNA fusions, and most of them respond better to chemotherapy and radiation than those who lack deletions in chromosomes 1 and 19." But evidence of a so-called "second hit" has been elusive, and researchers have been so far unable to pinpoint the specific gene mutations that allow for the development of this cancer. Now the team plans to conduct a trial to compare the prognostic favorability of patients with CIC and FUBP1 mutations compared to patients with the chromosomal fusion, the press release says. "We can focus now on when these mutations develop during tumor formation, whether they can guide prognosis, and how they might form targets for therapy," says Johns Hopkins' Chetan Bettegowda.

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