Molecular Pathogenesis of Low-Grade Glioma

Overview

Journal Neurosurg Clin N Am

Specialty Neurosurgery

Date 2018 Nov 25

PMID 30470401

Citations 18

Authors

Devin Bready

Dimitris G Placantonakis

Affiliations

Soon will be listed here.

Abstract

Advances in genome sequencing have elucidated the genetics of low-grade glioma. Available evidence indicates a neomorphic mutation in isocitrate dehydrogenase (IDH) initiates gliomagenesis. Mutant IDH produces the oncometabolite 2-hydroxyglutarate, which inhibits enzymes that demethylate genomic DNA and histones. Recent findings by the authors and others suggest the ensuing hypermethylation alters chromatin conformation and the transcription factor landscape in brain progenitor cells, leading to a block in differentiation and tumor initiation. Work in preclinical models has identified selective metabolic and molecular vulnerabilities of low-grade glioma. These new concepts will trigger a wave of innovative clinical trials in the near future.

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