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Series GSE45198 Query DataSets for GSE45198
Status Public on Apr 04, 2013
Title An Inhibitor of Mutant IDH1 Delays Growth and Promotes Differentiation of Glioma Cells Methylation Data for Xenograft Samples
Organism Homo sapiens
Experiment type Methylation profiling by array
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.
Overall design Xenograft experiments were carried out with treatment cohorts of vehicle, 150mg/kg/day, 450mg/kg/day. After the indicated tumors were harvested and genomic DNA was extracted and analyzed by the Illumina 450k Methylation array.
Contributor(s) Rohle DA, Mellinghoff IK
Citation(s) 23558169
Submission date Mar 15, 2013
Last update date Mar 22, 2019
Contact name Daniel Rohle
Organization name Memorial Sloan Kettering Cancer Center
Department The Human Oncology and Pathogenesis Program
Lab Ingo Mellinghoff Lab
Street address 1275 York Avenue
City New York
State/province NY
ZIP/Postal code 10065
Country USA
Platforms (1)
GPL13534 Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482)
Samples (28)
GSM1098985 vehicle m1
GSM1098986 150mg/kg AGI-5198 m11
GSM1098987 450mg/kg AGI-5198 m31
This SubSeries is part of SuperSeries:
GSE45200 An Inhibitor of Mutant IDH1 Delays Growth and Promotes Differentiation of Glioma Cells
BioProject PRJNA193200

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SOFT formatted family file(s) SOFTHelp
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Supplementary file Size Download File type/resource
GSE45198_RAW.tar 183.1 Mb (http)(custom) TAR
GSE45198_signals.txt.gz 64.1 Mb (ftp)(http) TXT
Processed data included within Sample table

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