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| Status |
Public on Jul 08, 2020 |
| Title |
Metabolic Regulation of the Epigenome Drives Lethal Infantile Ependymoma |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by genome tiling array
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| Summary |
Posterior fossa type A (PFA) ependymomas are a lethal glial malignancy of the hindbrain found in babies and toddlers. Lacking any highly recurrent somatic mutations, PFAs have been proposed as a largely epigenetically driven tumor type. An almost complete lack of model systems has inhibited discovery of novel PFA therapies. Both in vitro and in vivo, the PFA hypoxic microenvironment controls the availability of specific metabolites to diminish histone methylation, and to increase both histone demethylation and acetylation at H3K27. PFA ependymoma initiates from a cell lineage in the first trimester of human development where there is a known hypoxic microenvironment. Unique to PFA cells, transient exposure to ambient oxygen results in irreversible cellular toxicity. PFA tumors exhibit a low basal level of H3K27me3, and paradoxically inhibition of H3K27 methylation shows significant and specific activity against PFA. Targeting metabolism and/or the epigenome presents a unique opportunity for rational therapy for infants with PFA ependymoma.
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| Overall design |
Bisulphite converted DNA from each sample was hybridised to the Illumina Infinium EPIC Human Methylation BeadChip.
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| Contributor(s) |
Michealraj KA, Kumar SA, Kim LJ, Guilhamon P, Mack SC, Agnihotri S, Rich JN, Taylor MD |
| Citation(s) |
32445698 |
| Submission date |
Mar 05, 2020 |
| Last update date |
Jul 08, 2020 |
| Contact name |
Paul Guilhamon |
| Organization name |
SickKids
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| Street address |
686 Bay Street
|
| City |
Toronto |
| State/province |
ON |
| ZIP/Postal code |
M5G0A4 |
| Country |
Canada |
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| Platforms (1) |
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| Samples (10)
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| Relations |
| BioProject |
PRJNA610567 |
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