An epigenetic mechanism in which gain-of-function IDH mutations promote gliomagenesis by disrupting chromosomal topology is presented, with IDH mutations causing the binding sites of the methylation-sensitive insulator CTCF to become hypermethylated; disruption of a CTCF boundary near the glioma oncogene PDGFRA allows a constitutive enhancer to contact and activate the oncogene aberrantly.
- William A. Flavahan
- Yotam Drier
- Bradley E. Bernstein
