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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."

The Scan

And a Fourth?

A fourth dose of the Pfizer-BioNTech SARS-CoV-2 vaccine in an Israeli study increased antibody levels but did not prevent Omicron variant infections, according to the Financial Times.

For Better Science Software

A virtual institute funded by former Google CEO Eric Schmidt's philanthropy aims to lure software engineers to academia, Science reports.

Recommendation Explanations

The New York Times writes that the US Centers for Disease Control and Prevention is straining to both make and explain decisions based on limited information.

Genome Research Papers on De Novo Mutation Rates, Polyploid Genotyping, Oncogene Epigenomic Translocation

In Genome Research this week: de novo mutations rates in hemoglobin subunits, analysis of variant calling methods for polyploid plants, and more.