Epigenetic regulation of metabolic adaptation predicts response to Inositol hexakisphosphate (IP6) treatment in Group 4 medulloblastoma (HumanMethylation850)
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ABSTRACT: Deregulation of chromatin modifiers plays an essential role in the pathogenesis of medulloblastoma (MB), the most common paediatric malignant brain tumour. Here, we identify a BMI1-dependent sensitivity to deregulation of inositol metabolism in a proportion of medulloblastoma. We demonstrate mTOR pathway activation and metabolic adaptation specifically in medulloblastoma of the molecular subgroup G4 characterised by a BMI1High;CHD7Low signature and show this can be counteracted by IP6 treatment. Finally, we demonstrate that IP6 synergises with cisplatin to enhance its cytotoxicity in vitro and extends survival in a pre-clinical BMI1High;CHD7Low xenograft model.
ORGANISM(S): Homo sapiens
PROVIDER: GSE155962 | GEO | 2021/03/04
REPOSITORIES: GEO
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