Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Isocitrate dehydrogenase 1 mutations drive human gliomagenesis, probably through neomorphic enzyme activity that produces D-2-hydroxyglutarate. To model this disease, we conditionally expressed Idh1R132H in the subventricular zone (SVZ) of the adult mouse brain. The mice developed hydrocephalus and grossly dilated lateral ventricles, with accumulation of 2-hydroxyglutarate and reduced α-ketoglutarate. Stem and transit amplifying/progenitor cell populations were expanded, and proliferation increased. Cells expressing SVZ markers infiltrated surrounding brain regions. SVZ cells also gave rise to proliferative subventricular nodules. DNA methylation was globally increased, while hydroxymethylation was decreased. Mutant SVZ cells overexpressed Wnt, cell-cycle and stem cell genes, and shared an expression signature with human gliomas. Idh1R132H mutation in the major adult neurogenic stem cell niche causes a phenotype resembling gliomagenesis.

Original publication

DOI

10.1016/j.ccell.2016.08.017

Type

Journal article

Journal

Cancer Cell

Publication Date

10/10/2016

Volume

30

Pages

578 - 594

Keywords

DNA (hydroxy)methylation, Wnt, glioma, hydroxyglutarate, hydroxylase, isocitrate dehydrogenase, oncometabolite, stem cell, subventricular zone, α-ketoglutarate, Animals, Brain Neoplasms, DNA Methylation, Glioma, Isocitrate Dehydrogenase, Lateral Ventricles, Mice, Mice, Transgenic, Mutation, Neoplastic Stem Cells, Stem Cell Niche, Transcriptome