Temporal and Clonal Progression in Pediatric Ependymoma
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PROVIDER: PRJNA408011 | ENA |
REPOSITORIES: ENA
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Project description:Temporal and Clonal Progression in Pediatric Ependymoma
| PRJNA408012 | ENA
Project description:Pediatric ependymoma has relatively low frequencies of DNA mutations, which suggest that epigenetics may drive tumors. However, the epigenetic mechanisms for recurrent ependymoma are still poorly understood. Here, we performed longitudinal and comprehensive DNA methylation and gene expression analysis for recurrent pediatric ependymoma tumors from 10 patients, total 46 DNA methylomes (including primary tumors and matched recurrent tumors; normal pediatric brain tissues and PDOX tumors). Both RELA and PFA tumors maintained the subtype DNA methylation signatures during repeated relapses. We further identified the potential DNA methylation predictors, drivers and boosters and their potential regulated genes for recurrent ependymoma tumors. Increased DNA methylation levels within H3K4me1 enriched regions indicates disturbed functions of LSD1 gene in recurrent ependymoma tumors. Combining novel LSD1 inhibitor SYC-836 with radiation (XRT) significantly prolonged animal survival times in PDOX models of recurrent PFA ependymoma. Our PDOX models provide a unique platform for preclinical testing drugs and development of new therapy for pediatric recurrent ependymoma.
2022-07-12 | GSE156619 | GEO
Project description:We compared genomic characteristics of primary and first recurrent pediatric ependymoma to identify sub-group specific differences.
2016-09-11 | GSE50876 | GEO
Project description:ZFTA-RELA is the most recurrent genetic alteration seen in ependymoma, and sufficient to initiate tumors when expressed during mouse brain development. Despite ZFTA-RELA’s potent oncogenic potential, ZFTA-RELA gene fusions are observed exclusively in ependymoma and have never been documented in any other adult or pediatric malignancy. We hypothesized that specific chromatin modules accessible during brain development would render specific cells-of-origin at increased risk of transformation by ZFTA fusion proteins. To this end we performed integrated single cell ATAC and RNA-seq analysis (referred to as scMultimome) in mouse and human ependymoma tumors driven by the ZFTA-RELA fusion. We demonstrate that specific epi-developmental programs present in radial glia and regulated by Plagl1 are at direct risk of transformation. Oncoprotein engagement of this chromatin module leads to persistent oncogene expression, a failure to halt cellular proliferation, and initiate terminal cellular differentiation. Surprisingly, ependymomas exhibit significant heterogeneity across lineage differentiation programs, and continued activation of Plagl1 networks in differentiated cell types such as tumor neuronal-like cells contribute to tumor progression. These findings implicate specific chromatin modules in cells of origin as critical mediators of ependymoma initiation. Persistent activation and erosion of developmetn lineage programs serve as drivers of tumor development and contribute to the cellular heterogeneity of the tumor microenvironment.
2026-03-25 | GSE269937 | GEO
Project description:Epigenetic Landscape of Pediatric Ependymoma Recurrence
| PRJNA658524 | ENA
Project description:We compared molecular characteristics of primary and recurrent pediatric ependymoma to identify sub-group specific differences. Gene expression profiles were used to identify unique immunobiologic sub-types of posterior fossa pediatric ependymoma. Gene expression profiles were generated from surgical tumor (ependymoma) (n=65) using Affymetrix HG-U133plus2 chips (Platform GPL570). Normalization was performed on our entire cohort of ependymoma. Of the 65 samples, a sub-set of 58 were used in the corresponding manuscript. Excluded samples are noted. Gene expression profiles were filtered to obtain gene expression of key immune cell markers. Comparative analyses between tumor samples were used to identifiy unique immunobiology between posterior fossa sub-groups.
2013-08-30 | E-GEOD-50385 | biostudies-arrayexpress
Project description:We compared molecular characteristics of primary and recurrent pediatric ependymoma to identify sub-group specific differences. Gene expression profiles were used to identify unique immunobiologic sub-types of posterior fossa pediatric ependymoma.
2013-08-30 | GSE50385 | GEO
Project description:Single cell multiome atlas of pediatric ependymoma
| PRJNA1124137 | ENA
Project description:Single-cell RNA-seq of pediatric ependymoma
| PRJNA593551 | ENA
Project description:Ependymoma (EPN) is the third most common central nervous system (CNS) tumor in childhood and, recently, has been classified in nine robust molecular subgroups (Pajtler et al., 2015). However, molecular and clinical features of pediatric EPNs from Brazilian cohorts remain unexplored. Herein, we aimed to analyze the gene expression profile among three different molecular subgroups: ST-EPN-RELA, ST-EPN-YAP1 and PF-EPN-A.
2023-03-03 | GSE181162 | GEO