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| 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
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| 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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| 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.
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| Contributor(s) |
Rohle DA, Mellinghoff IK |
| Citation(s) |
23558169 |
| Submission date |
Mar 15, 2013 |
| Last update date |
Mar 22, 2019 |
| Contact name |
Daniel Rohle |
| E-mail(s) |
rohled@mskcc.org
|
| Organization name |
Memorial Sloan Kettering Cancer Center
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| Department |
The Human Oncology and Pathogenesis Program
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| Lab |
Ingo Mellinghoff Lab
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| Street address |
1275 York Avenue
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10065 |
| Country |
USA |
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| Platforms (1) |
| GPL13534 |
Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482) |
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| Samples (28)
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| This SubSeries is part of SuperSeries: |
| GSE45200 |
An Inhibitor of Mutant IDH1 Delays Growth and Promotes Differentiation of Glioma Cells |
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| Relations |
| BioProject |
PRJNA193200 |
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