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PRC2 Heterogeneity Drives Tumor Growth in Medulloblastoma

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE206009 | GEO | 2022/06/18

REPOSITORIES: GEO

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PRC2 Heterogeneity Drives Tumor Growth in Medulloblastoma [Human]

Project description:Intratumor epigenetic heterogeneity is emerging as a key mechanism underlying tumor evolution and drug resistance. Epigenetic abnormalities frequently occur in medulloblastoma, the most common childhood malignant brain tumor. Medulloblastoma is classified into four subtypes including SHH medulloblastoma, which is characterized by elevated SHH signaling and a cerebellum granule neuron precursor (CGNP) cell-of-origin. Here we report that the histone H3K27 methyltransferase polycomb repressor complex 2 (PRC2) is often heterogeneous within individual SHH medulloblastoma tumors. In mouse models, complete deletion of the PRC2 core subunit EED inhibited medulloblastoma growth, while a mosaic deletion of EED significantly enhanced tumor growth. EED is intrinsically required for CGNP maintenance by inhibiting both neural differentiation and cell death. Complete deletion of EED led to CGNP depletion and reduced occurrence of medulloblastoma. Surprisingly, medulloblastomas with mosaic EED levels grew faster than control wildtype tumors and expressed increased levels of oncogenes such as Igf2, which is directly repressed by PRC2 and has been demonstrated to be both necessary and sufficient for SHH medulloblastoma progression. IGF2 mediated the oncogenic effects of PRC2 heterogeneity in tumor growth. Assessing clones of a human medulloblastoma cell line with different EED levels confirmed that EEDlow cells can stimulate the growth of EEDhigh cells through paracrine IGF2 signaling. Thus, PRC2 heterogeneity plays an oncogenic role in medulloblastoma through both intrinsic growth competence and non-cell autonomous mechanisms in distinct tumor subclones.

2022-06-18 | GSE206000 | GEO

PRC2 Heterogeneity Drives Tumor Growth in Medulloblastoma [mouse]

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PRC2 Heterogeneity Drives Tumor Growth in Medulloblastoma

Project description:PRC2 Heterogeneity Drives Tumor Growth in Medulloblastoma

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Variant PRC1 complex dependent H2A ubiquitylation drives PRC2 recruitment and polycomb domain formation

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-05-27 | E-GEOD-55698 | biostudies-arrayexpress

PRC2 Heterogeneity Drives Tumor Growth in Medulloblastoma [Human]

Project description:PRC2 Heterogeneity Drives Tumor Growth in Medulloblastoma [Human]

| PRJNA848779 | ENA

PRC2 Heterogeneity Drives Tumor Growth in Medulloblastoma [mouse]

Project description:PRC2 Heterogeneity Drives Tumor Growth in Medulloblastoma [mouse]

| PRJNA848790 | ENA

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Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

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Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-08-24 | E-GEOD-53248 | biostudies-arrayexpress

Endocan-PDGFRα mediated signaling drives glioblastoma spatial heterogeneity and influences tumor vasculature/radioresistance

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

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

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