Metabolic regulation of the epigenome drives lethal infantile ependymoma [Cut&Run]
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ABSTRACT:
PROVIDER: PRJNA612185 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11294234.fastq.gz | Fastqsanger.gz | |||
| SRR11294235.fastq.gz | Fastqsanger.gz | |||
| SRR11294236.fastq.gz | Fastqsanger.gz | |||
| SRR11294237.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Metabolic Regulation of the Epigenome Drives Lethal Infantile Ependymoma
| PRJNA610567 | ENA
Project description: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.
2020-08-13 | PXD018191 | Pride
Project description:PFA (posterior fossa group A) ependymomas are a lethal glial malignancy of the hindbrain found in infants 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.
2020-03-18 | GSE146858 | GEO
Project description: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.
2020-07-08 | GSE146426 | GEO
Project description:Posterior fossa A (PFA) ependymomas are lethal malignancies of the hindbrain in infants and toddlers. Lacking highly recurrent somatic mutations, PFA ependymomas are proposed to be epigenetically driven tumors for which model systems are lacking. Here we demonstrate that PFA ependymomas are maintained under hypoxia, associated with restricted availability of specific metabolites to diminish histone methylation, and increase histone demethylation and acetylation at histone 3 lysine 27 (H3K27). PFA ependymomas initiate from a cell lineage in the first trimester of human development that resides in restricted oxygen. Unlike other ependymomas, transient exposure of PFA cells to ambient oxygen induces irreversible cellular toxicity. PFA tumors exhibit a low basal level of H3K27me3, and, paradoxically, inhibition of H3K27 methylation specifically disrupts PFA tumor growth. Targeting metabolism and/or the epigenome presents a unique opportunity for rational therapy for infants with PFA ependymoma.
| S-EPMC10782558 | biostudies-literature
Project description:Epigenome analysis of ependymoma cell lines
| PRJNA436983 | ENA
Project description:Genome sequencing studies have uncovered the most frequent mutations in cancer and novel targets for therapy. While successful in many tumors, this approach has failed in others. Lethal infant ependymomas (Group A) lies at the far end of this spectrum with no recurrent focal genomic alterations, no recurrent somatic mutations, and no clear driver for targeted therapy. Despite a paucity of genetic aberrations, Group A ependymomas demonstrate widespread epigenetic alterations. We therefore sought to interrogate the oncogenic drivers of ependymoma by characterizing the enhancer landscapes of 30 primary tumors. Super enhancer (SE) mapping revealed novel ependymoma oncogenes such as PAX6, SKI, and FGFRL1 and uncovered subgroup specific SE lesions across ependymoma, specifically, in Group A such as PAX3, MEIS1, and IGF2BP1. Finally, we identified SE associated gene dependencies that maintain FGFR1 and WEE1 expression in ependymoma, demonstrating the utility of SE lesions to predict novel targets for cancer therapy.
2018-11-15 | GSE75017 | GEO
Project description:The goal of this study was to identify new mutations in the ENPP1 gene that produce infantile arterial calcification and fetal demise. A stillborn (proband) was diagnosed with infantile arterial calcification. Mutations in the ENPP1 gene account for ~80% of the cases of infantile arterial calcification through loss of function in both alleles (recessive inheritance).
2011-01-26 | GSE26860 | GEO
Project description:We compared molecular characteristics of primary and recurrent pediatric ependymoma to identify sub-group specific differences. Gene expression profiles were used to identify unique immunobiologic sub-types of posterior fossa pediatric ependymoma. Gene expression profiles were generated from surgical tumor (ependymoma) (n=65) using Affymetrix HG-U133plus2 chips (Platform GPL570). Normalization was performed on our entire cohort of ependymoma. Of the 65 samples, a sub-set of 58 were used in the corresponding manuscript. Excluded samples are noted. Gene expression profiles were filtered to obtain gene expression of key immune cell markers. Comparative analyses between tumor samples were used to identifiy unique immunobiology between posterior fossa sub-groups.
2013-08-30 | E-GEOD-50385 | biostudies-arrayexpress
Project description:We report an infantile case of midline ‘supratentorial ependymoma ZFTA fusion-positive’ involving both the infra- and the supra-tentorial compartments (i.e., cerebellar vermis, pons and midbrain). The radiological features, i.e., the upward displacement and compression of the supratentorial anatomical structures and the infiltrative margins of the tumour towards the cerebellar vermis, suggested an infratentorial origin of the lesion with secondary involvement of the supratentorial compartment. This case adds to the limited literature of non-hemispheric ‘supratentorial ependymoma ZFTA fusion-positive’ occurring in midline structures, both supratentorial (pineal region, thalamus) and infratentorial (cervico-medullary region and spinal cord), and in the cerebellum. These cases highlight the need to consider this entity in the differential diagnosis of paediatric non-hemispheric lesions and raise the question of whether the inclusion of the location within the WHO definition of this tumour type may be too restrictive
2023-01-01 | GSE220932 | GEO