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Epigenomic Alterations Define Lethal CIMP-positive Ependymomas of Infancy

ABSTRACT: 1) Illumina 450K methylation profiles-48 posterior fossa ependymomas

ORGANISM(S): Homo sapiens

PROVIDER: GSE45353 | GEO | 2014/03/25

SECONDARY ACCESSION(S): PRJNA193601

REPOSITORIES: GEO

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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

2014-03-25 | E-GEOD-45353 | biostudies-arrayexpress

Epigenomic Alterations Define Lethal CIMP positive Ependymomas of Infancy

Project description:Ependymomas are common childhood brain tumors that occur throughout the nervous system, but are most common in the pediatric hindbrain. Current standard therapy comprises surgery and radiation, but not cytotoxic chemotherapy as it does not further increase survival. Whole-genome and whole-exome sequencing of 47 hindbrain ependymomas reveals an extremely low mutation rate, and zero significant recurrent somatic SNVs. While devoid of recurrent SNVs and focal copy number aberrations, poor prognosis hindbrain ependymomas exhibit a CpG island methylator phenotype (CIMP). Transcriptional silencing driven by CpG methylation converges exclusively on targets of the polycomb repressor complex 2 (PRC2) that represses expression of differentiation genes through tri-methylation of H3K27. CIMP-positive (CIMP+) hindbrain ependymomas are responsive to clinical drugs that target either DNA or H3K27 methylation both in vitro and in vivo. We conclude that epigenetic modifiers are the first rational therapeutic candidates for this deadly malignancy, which is epigenetically de-regulated but genetically bland. 10 primary posterior fossa ependymomas have been analyzed

2014-03-15 | E-GEOD-55920 | biostudies-arrayexpress

Epigenomic Alterations Define Lethal CIMP positive Ependymomas of Infancy

2014-03-15 | GSE55920 | GEO

Epigenomic alterations define lethal CIMP-positive ependymomas of infancy.

Project description: Not available

| S-EPMC4174313 | biostudies-literature

Epigenomic alterations define lethal CIMP-positive ependymomas of infancy

Project description:Ependymomas are common childhood brain tumours that occur throughout the nervous system, but are most common in the paediatric hindbrain. Current standard therapy comprises surgery and radiation, but not cytotoxic chemotherapy as it does not further increase survival. Whole-genome and whole-exome sequencing of 47 hindbrain ependymomas reveals an extremely low mutation rate, and zero significant recurrent somatic single nucleotide variants. Although devoid of recurrent single nucleotide variants and focal copy number aberrations, poor-prognosis hindbrain ependymomas exhibit a CpG island methylator phenotype. Transcriptional silencing driven by CpG methylation converges exclusively on targets of the Polycomb repressive complex 2 which represses expression of differentiation genes through trimethylation of H3K27. CpG island methylator phenotype-positive hindbrain ependymomas are responsive to clinical drugs that target either DNA or H3K27 methylation both in vitro and in vivo. We conclude that epigenetic modifiers are the first rational therapeutic candidates for this deadly malignancy, which is epigenetically deregulated but genetically bland.

| EGAS00001000443 | EGA

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

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 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 | GSE89446 | GEO

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

2016-11-23 | GSE89448 | GEO

Targeting integrated metabolic and epigenetic pathways in lethal childhood ependymomas

Project description:Childhood Posterior Fossa-A ependymomas (PFAs) have limited treatment options. Integrated metabolic/epigenetic analyses performed to discover therapeutic targets in PFAs demonstrated enhanced glycolysis and TCA-cycle metabolism. PFAs exhibit low H3K27me3, as in H3K27M gliomas. Therefore, we subjected them to panobinostat which kills H3K27M cells, along with the metabolic inhibitor metformin. Combined treatment increased H3K27me3, suppressed metabolism and demonstrated potent therapeutic efficacy in vitro and in vivo, suggesting promising therapeutic strategies.

2022-07-01 | GSE134572 | GEO

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