期刊
NEUROSURGERY CLINICS OF NORTH AMERICA
卷 30, 期 1, 页码 17-+出版社
W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1016/j.nec.2018.08.011
关键词
Low-grade glioma; Astrocytoma; Oligodendroglioma; Mutant IDH
资金
- NIGMS NIH HHS [T32 GM007308] Funding Source: Medline
- NINDS NIH HHS [R01 NS102665, R03 NS087349] Funding Source: Medline
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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