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

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

PROVIDER: PRJNA352237 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR4841750_1.fastq.gz	Fastqsanger.gz
	SRR4841750_2.fastq.gz	Fastqsanger.gz
	SRR4849170_1.fastq.gz	Fastqsanger.gz
	SRR4849170_2.fastq.gz	Fastqsanger.gz
	SRR4849180_1.fastq.gz	Fastqsanger.gz

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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.

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Low 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.

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

2016-11-23 | GSE89448 | 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.

2016-11-23 | GSE89451 | GEO

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: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

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

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

2016-11-23 | GSE89452 | GEO

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.

2022-05-01 | GSE196013 | GEO

Homo sapiens

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

| PRJNA347565 | ENA

EZHIP / CXorf67 mimics K27M mutated oncohistones and functions as an intrinsic inhibitor of PRC2 function in aggressive posterior fossa ependymoma

Project description:Posterior fossa A (PFA) ependymomas comprise one out of nine molecular groups of ependymoma. PFA tumors are mainly diagnosed in infants and young children, show a poor prognosis and are characterized by a lack of the repressive histone H3 lysine 27 trimethylation (H3K27me3) mark. Recently, we reported CXorf67 overexpression as hallmark of PFA ependymoma and showed that CXorf67 can interact with EZH2 thereby inhibiting polycomb repressive complex 2 (PRC2). Here, we report that the inhibitory mechanism of this interaction is similar as in diffuse midline gliomas harboring H3K27M mutations. A small, highly conserved peptide sequence located in the C-terminal region of CXorf67 mimics the H3K27M peptide and binds to the SET domain of EZH2. This interaction blocks EZH2 methyltransferase activity and causes H3K27 hypomethylation, an oncogenic mechanism that may be exploited for targeted therapy in PFA ependymoma. Based on its function, we have renamed CXorf67 into EZH2 Inhibitory Protein (EZHIP).

2019-07-08 | PXD012318 | Pride

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