GEO series

An Inhibitor of Mutant IDH1 Delays Growth and Promotes Differentiation of Glioma Cells Methylation Data for Xenograft Samples

GSE45198 Homo sapiens Methylation profiling by array 28 samples Submitted 2013/04/04 Platform GPL13534

Summary

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.

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Direct links to NCBI, no account and no request form: the whole study as GSE45198_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 28 samples.

Whole study · RAW.tar ↓ Series matrix ↓ All supplementary files ↗

Also filed as BioProject PRJNA193200. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 23558169) ↗

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