Demethylation and epigenetic modification with 5-azacytidine reduces IDH1 mutant glioma growth in combination with temozolomide.

ABSTRACT:

Background

Isocitrate deyhydrogenase (IDH) mutant glioma comprises the majority of grades II-III gliomas and nearly all secondary glioblastomas. These progressive gliomas arise from mutations in IDH1 or IDH2 that pathologically produce D-2-hydroxyglutarate (2HG), which interferes with cell reactions using alpha ketoglutarate, leading to a hypermethylated genome and epigenetic dysregulation of gene expression initiating tumorigenesis.

Methods

Human IDH1 wild type (wt) and IDH1 R132H cell lines and patient-derived xenografts (PDXs) were used to evaluate the FDA-approved DNA demethylating agent 5-azacytidine (5-aza). Cell growth, protein and gene expression, chromatin immunoprecipitation, and nucleosome position assays were performed in 5-aza treated cells. To evaluate antitumo

SUBMITTER: Yamashita AS 

PROVIDER: S-EPMC6374765 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature