Molecular Pathogenesis of Low-Grade Glioma.

Neurosurg Clin N Am 2019 Jan;30(1):17-25

Department of Neurosurgery, Kimmel Center for Stem Cell Biology, Laura and Isaac Perlmutter Cancer Center, Neuroscience Institute, Brain Tumor Center, NYU School of Medicine, 530 First Avenue, Skirball 8R, New York, NY 10016, USA. Electronic address:

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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Source
https://linkinghub.elsevier.com/retrieve/pii/S10423680183091
Publisher Site
http://dx.doi.org/10.1016/j.nec.2018.08.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6260953PMC
January 2019
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