Unknown

Dataset Information

0

An Inhibitor of Mutant IDH1 Delays Growth and Promotes Differentiation of Glioma Cells Methylation Data for In Vitro Model


ABSTRACT: The recent discovery of mutations in metabolic enzymes has rekindled interest in harnessing the altered metabolism of cancer cells for cancer therapy. One potential drug target is isocitrate dehydrogenase 1 (IDH1) which is mutated in multiple human cancers. Here, we examine the role of mutant IDH1 in fully transformed cells with endogenous IDH1 mutations. A selective R132H-IDH1 inhibitor (AGI-5198) identified through a high-throughput screen dose-dependently blocked the ability of the mutant enzyme (mIDH1) to produce R-2-hydroxyglutarate (R-2HG). Under conditions of near complete R-2HG inhibition, the mIDH1 inhibitor induced demethylation of histone H3K9M3 and expression of genes associated with gliogenic differentiation. Blockade of mIDH1 impaired the growth of IDH1-mutant - but not IDH1-wildtype – glioma cells without appreciable changes in genome wide DNA methylation. These data suggest that mIDH1 may promote glioma growth through mechanisms beyond its well-characterized epigenetic effects. Samples were maintained in either DMSO or 1.5uM 5198 for 2 passages up to 20 passages. Biological replicates for each passage and treatment was collected and genomic DNA was extracted and analyzed on the Illumina 450K Methylation platform for a total of 16 samples.

SUBMITTER: Daniel Rohle 

PROVIDER: E-GEOD-45199 | BioStudies | 2013-04-04

SECONDARY ACCESSION(S): GSE45199

REPOSITORIES: biostudies

Similar Datasets

2013-01-01 | S-EPMC3985613 | BioStudies
2013-04-04 | E-GEOD-45199 | ArrayExpress
2013-04-04 | E-GEOD-45198 | ArrayExpress
2013-04-04 | E-GEOD-45197 | ArrayExpress
2015-01-01 | S-EPMC4569544 | BioStudies
1000-01-01 | S-EPMC5063515 | BioStudies
2018-01-01 | S-EPMC5902553 | BioStudies
2020-01-01 | S-EPMC7584476 | BioStudies
2013-01-01 | S-EPMC3548957 | BioStudies
2017-01-01 | S-EPMC5435119 | BioStudies