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Shouldn't Be Over Here

Mutations in the housekeeping gene IDH may mediate the development of brain tumors by increasing methylation throughout the genome and disrupting usual DNA folding patterns, a Broad Institute-led team of researchers reports in Nature.

In particular, the Broad's Bradley Bernstein and his colleagues found that gain-of-function mutations in IDH lead to genome-wide hypermethylation of CTCF binding sites and the deregulation of boundary elements that divide different topological domains. The elimination of a boundary near PDGFRA, a glioma oncogene, enables an enhancer then to swing by and activate it.

Bernstein tells the New York Times that this way of becoming cancerous likely isn't limited to brain tumors.

Such excessive methylation also suggests a possible treatment, he notes. As he and his colleagues report in Nature, they found that treating patient-derived IDH mutant gliomaspheres with a demethylating agent like the first-generation chemotherapy drug 5-azacytidine partially restored insulator function and downregulated PDGFRA.

But first, Bernstein tells the Times, there needs to be a way to detect an overabundance of methyl tags and the breakdown of DNA topological domains.

"I am biased, obviously," Bernstein says before adding that he is "really optimistic about the potential of this information."