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Low H3K27me3 and DNA hypomethylation define poorly prognostic pediatric posterior fossa ependymomas

ABSTRACT: A subgroup of Posterior fossa ependymomas show reduced H3K27me3, global DNA hypomethylation, are more invasive, exhibit poor prognosis and epigenetically deregulated genes converge on radial glial factors, suggesting developing cerebellar radial glia as candidate cells-of-origin.

ORGANISM(S): Homo sapiens

PROVIDER: GSE89446 | GEO | 2016/11/23

SECONDARY ACCESSION(S): PRJNA352234

REPOSITORIES: GEO

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DNA hypomethylation define poorly prognostic pediatric posterior fossa ependymomas

Project description:A subset of genomically silent childhood posterior fossa ependymomas show reduced H3K27me3, global DNA hypomethylation, are more invasive, exhibit poor prognosis and epigenetically deregulated genes converge on radial glial factors, suggesting developing cerebellar radial glia as candidate cells-of-origin.

2016-11-28 | GSE87779 | GEO

Low H3K27me3 define poorly prognostic pediatric posterior fossa ependymomas

Project description:A subgroup of Posterior fossa ependymomas show reduced H3K27me3 are more invasive, exhibit poor prognosis and epigenetically deregulated genes converge on radial glial factors, suggesting developing cerebellar radial glia as candidate cells-of-origin.

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Global reduction in H3K27me3 and DNA hypomethylation define poorly prognostic pediatric posterior fossa ependymomas

Project description:A subgroup of Posterior fossa ependymomas show reduced H3K27me3, global DNA hypomethylation, are more invasive, exhibit poor prognosis and epigenetically deregulated genes converge on radial glial factors, suggesting developing cerebellar radial glia as candidate cells-of-origin.

2016-11-23 | GSE89448 | GEO

Lowered H3K27me3 and DNA hypomethylation define poorly prognostic pediatric posterior fossa ependymomas

Project description:Lowered H3K27me3 and DNA hypomethylation define poorly prognostic pediatric posterior fossa ependymomas

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Lowered H3K27me3 and DNA hypomethylation define poorly prognostic pediatric posterior fossa ependymomas.

Project description:Childhood posterior fossa (PF) ependymomas cause substantial morbidity and mortality. These tumors lack recurrent genetic mutations, but a subset of these ependymomas exhibits CpG island (CpGi) hypermethylation [PF group A (PFA)], implicating epigenetic alterations in their pathogenesis. Further, histological grade does not reliably predict prognosis, highlighting the importance of developing more robust prognostic markers. We discovered global H3K27me3 reduction in a subset of these tumors (PF-ve ependymomas) analogous to H3K27M mutant gliomas. PF-ve tumors exhibited many clinical and biological similarities with PFA ependymomas. Genomic H3K27me3 distribution showed an inverse relationship with CpGi methylation, suggesting that CpGi hypermethylation drives low H3K27me3 in PF-ve ependymomas. Despite CpGi hypermethylation and global H3K27me3 reduction, these tumors showed DNA hypomethylation in the rest of the genome and exhibited increased H3K27me3 genomic enrichment at limited genomic loci similar to H3K27M mutant gliomas. Combined integrative analysis of PF-ve ependymomas with H3K27M gliomas uncovered common epigenetic deregulation of select factors that control radial glial biology, and PF radial glia in early human development exhibited reduced H3K27me3. Finally, H3K27me3 immunostaining served as a biomarker of poor prognosis and delineated radiologically invasive tumors, suggesting that reduced H3K27me3 may be a prognostic indicator in PF ependymomas.

| S-EPMC5123566 | biostudies-literature

Gene expression data from posterior fossa ependymomas

Project description:We have discovered two major molecular subgroups of PFA molecular group posterior fossa ependymomas by DNA methylation profiling. These are also distinguished by gene expression profiling using Affymetrix U133v2 arrays with correspondence to data generated by DNA methylation profiling.

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Lowered H3K27me3 and DNA hypomethylation define poorly prognostic pediatric posterior fossa ependymomas

Project description:This SuperSeries is composed of the SubSeries listed below.

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Epigenomic Alterations Define Lethal CIMP-positive Ependymomas of Infancy

Project description:1) Illumina 450K methylation profiles-48 posterior fossa ependymomas NA

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ACVR1-mutant posterior fossa ependymoma

Project description:Genomewide DNA methylation array profiling of nine posterior fossa ependymomas harboring activating mutations in ACVR1. Two samples clustered with the PFA subtype and demonstrated H3K27me3 loss by immunohistochemistry, while the remaining 7 showed retained H3K27me3 and formed a methylation cluster distinct from other ependymal tumors. For these previsouly unpublished cases, the Illumina Infinium EPIC 850k Human DNA Methylation Beadchip was used to obtain DNA methylation profiles across approximately 850,000 CpG sites of genomic DNA extracted from formalin-fixed, paraffin-embedded tumor tissue.

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