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Global reduction in 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: GSE89448 | GEO | 2016/11/23

SECONDARY ACCESSION(S): PRJNA352240

REPOSITORIES: GEO

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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

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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.

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ACVR1-mutant posterior fossa ependymoma

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Project description:Gene expression (mRNA) profiling of human ependymomas Despite the histological similarity of ependymomas from throughout the neuraxis, the disease likely comprises multiple independent entities, each with a distinct molecular pathogenesis. Transcriptional profiling of two large independent cohorts of ependymoma reveals the existence of two demographically, transcriptionally, genetically, and clinically distinct groups of posterior fossa (PF) ependymoma. Group-A patients are younger, have laterally located tumors with a balanced genome, and are much more likely to exhibit recurrence, secondary metastasis, and death as compared to Group-B patients. Identification and optimization of immunohistochemical markers for PF ependymoma subgroups allowed validation of our findings on a third independent group of tumors using a human ependymoma tissue microarray, and provides a tool for prospective prognostication and stratification of PF ependymoma patients. We analyzed 102 primary ependymomas on the Affymetrix Exon 1.0ST platform (Gene Level).

2011-08-14 | E-GEOD-27279 | biostudies-arrayexpress

Delineation of Two Clinically and Molecularly Distinct Subgroups of Posterior Fossa Ependymoma.

Project description:Despite histological similarity of ependymomas from throughout the neuraxis, the disease likely comprises multiple independent entities, each with a distinct molecular pathogenesis. Transcriptional profiling of two large independent cohorts of ependymomas reveals the existence of two demographically, transcriptionally, genetically and clinically distinct groups of posterior fossa (PF) ependymoma. Group A patients are younger, have laterally located tumors with a balanced genome, and are much more likely to exhibit recurrence, metastasis, and death as compared to Group B patients. Identification and optimization of immunohistochemical markers for PF ependymoma subgroups allowed validation of our findings on a third group of independent ependymomas using a human ependymoma tissue microarray, and provides a tool for prospective prognostication and stratification of PF ependymoma patients. This SuperSeries is composed of the following subset Series: GSE27283: Human ependymoma samples [expression] GSE27286: Human ependymoma samples, Subgrouping [aCGH - German Cancer Research Center human 33K BAC array] Refer to individual Series

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