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Sox9 directs divergent epigenomic states in brain tumor subtypes (ChIP-Seq)

ABSTRACT: The goal of this study was to profile active H3K27ac marks between autochthonous mouse models of high-grade glioma (HGG) and ependymoma (EPN). Furthermore, with the objective of how transcription factor Sox9 affect H3K27ac states in these two models, we also profiled H3K27ac status between HGG and EPN after Sox9 overexpression (Sox9-GOF) or deletion (Sox9-LOF) in each of these models. In addition, we extended our studies to evaluate both H3K27ac and Sox9 states in human HGG and mouse EPN derived tumor cells.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE202960 | GEO | 2022/05/20

REPOSITORIES: GEO

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Sox9 directs divergent epigenomic states in brain tumor subtypes (RNA-Seq)

Project description:The goal of this study was to profile gene expression differences between autochthonous mouse models of high-grade glioma (HGG) and ependymoma (EPN). Furthermore, with the objective of how transcription factor Sox9 affect gene expression in these two models, we also profiled gene expression differences between HGG and EPN after Sox9 overexpression (Sox9-GOF) or deletion (Sox9-LOF) in each of these models.

2022-05-20 | GSE202958 | GEO

Sox9 directs divergent epigenomic states in brain tumor subtypes

Project description:Epigenetic dysregulation is a universal feature of cancer that results in altered patterns of gene expression that drive malignancy. Brain tumors exhibit subtype-specific epigenetic alterations, however the molecular mechanisms responsible for these diverse epigenetic states remain unclear. Here we show that the developmental transcription factor Sox9 differentially regulates epigenomic states in high-grade glioma (HGG) and ependymoma (EPN). These contrasting roles for Sox9 correspond with protein interactions with histone deacetylating complexes in HGG, and association with the Rela oncofusion in EPN. Together, our studies demonstrate how epigenomic states are differentially regulated in distinct subtypes of brain tumors, while revealing divergent roles for Sox9 in HGG and EPN tumorigenesis.

2022-07-13 | PXD033863 | Pride

RNA sequencing of posterior fossa ependymoma harboring 6q loss

Project description:Two distinct groups of posterior fossa ependymoma, PF-EPN-A and PF-EPN-B have been identified in children and are often associated with widely distinct outcomes. We have identified an ultra-high-risk PF-EPN-A ependymoma with 6q loss. We performed RNA sequencing of posterior fossa ependymoma A (PF-EPN-A) tumor samples with chromosome 6q loss and balanced to understand the differences in 6q loss at the transcriptomic level

2021-02-15 | GSE164292 | GEO

Investigation of the mechansim underlying the inflammatory phenotype in Group A ependymoma

Project description:Inflammatory response has been identified as a molecular signature of high-risk Group A ependymoma (EPN). To better understand the biology of this phenotype and aid therapeutic development, transcriptomic data from Group A and B EPN patient tumor samples, and additional malignant and normal brain data, were analyzed to identify the mechanism underlying EPN group A inflammation. Gene expression profiles of Group A and B EPN were contrasted to identify inflammatory transcriptional profiles (GSEA analysis). Candidate inflammatory mechanism genes were examined across a broader cohort of pediatric and adult brain tumor types and normal brain. Gene expression profiles were generated from surgical tumor and normal brain samples (n=149) using Affymetrix HG-U133plus2 chips (Platform GPL570).

2015-02-27 | E-GEOD-66354 | biostudies-arrayexpress

Adult intracranial ependymoma - relevance of DNA methylation profiling for diagnosis, prognosis and treatment

Project description:Background: A methylation-based classification of ependymoma has recently found broad application. However, the diagnostic advantage and implications for treatment decisions remain unclear. Here, we retrospectively evaluate the impact of surgery and radiotherapy on outcome after molecular reclassification of adult intracranial ependymomas. Methods: Tumors diagnosed as intracranial ependymomas from 170 adult patients collected from eight diagnostic institutions were subjected to DNA methylation profiling. Molecular classes, patient characteristics, and treatment were retrospectively correlated with progression-free survival (PFS). Results: The classifier indicated an ependymal tumor in 73.5%, a different tumor entity in 10.6% and non-classifiable tumors in 15.9% of cases, respectively. The most prevalent molecular classes were posterior fossa ependymoma group B (EPN-PFB, 32.9%), posterior fossa subependymoma (PF-SE, 25.9%), and supratentorial ZFTA fusion-positive ependymoma (EPN-ZFTA, 11.2%). With a median follow-up of 60.0 months, the 5- and 10-year-PFS rates were 64.5% and 41.8% for EPN-PFB, 67.4% and 45.2% for PF-SE and 60.3% and 60.3% for EPN-ZFTA. In EPN-PFB, but not in other molecular classes, gross total resection (p=0.009) and postoperative radiotherapy (p=0.007) were significantly associated with improved PFS in multivariable analysis. Histological tumor grading (WHO 2 vs. 3) was not a predictor of prognosis within molecularly defined ependymoma classes. Conclusions: DNA methylation profiling improves diagnostic accuracy and risk stratification in adult intracranial ependymoma. The molecular class of PF-SE is unexpectedly prevalent among adult tumors with ependymoma histology and relapsed as frequently as EPN-PFB, despite the supposed benign nature. Gross total resection and radiotherapy may represent key factors in determining the outcome of EPN-PFB patients.

2023-02-21 | GSE224218 | GEO

Arabidopsis thaliana

Project description:YODA lof and gof seedlings

| PRJNA88039 | ENA

Gene expression data from Brazilian pediatric ependymoma samples.

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

Ependymoma subpopulation lineages underlie clinical classification and outcome (microarray data set)

Project description:Introduction: single-cell RNA sequencing identified multiple subpopulations in childhood posterior fossa ependymoma. The contribution of individual neoplastic subpopulations to bulk tumor transcriptome-based molecular classification and patient outcome was estimated by deconvolution in a cohort of clinically-annotated primary and recurrent EPN samples. The abundance of EPN subpopulations was estimated in primary EPN samples and showed that the ratio of subpopulation fractions dictated assignment to the two main transcriptomic classification subgroups in childhood posterior fossa ependymoma. Longitudinal analysis revealed that subpopulation fractions changed between presentation and recurrence. Outcome analyses demonstrated that a different proportions of subpopulations were associated with differential survival.

2020-07-31 | GSE125861 | GEO

Characterization of Two Novel Ependymoma Cell Lines with Chromosome 1q gain derived from Posterior Fossa Tumors of Childhood

Project description:Introduction: Ependymoma (EPN) studies have revealed certain genetic markers, such as gain of chromosome 1q (1q+), as indicators of poor survival and high rate of recurrence. Development of novel therapeutics for EPN has been hampered by a lack of in vivo and in vivo models. We describe two unique 1q+ cell lines (811 and 928) derived from two children with metastatic, recurrent EPN. Both cell lines were characterized using histological, karyotypic and transcriptomic methods Transcriptomic analysis revealed that both lines, when cultured in 3D format, clustered closer to primary EPN tumors than monolayer format and with better fidelity of EPN-specific transcripts, namely those related to cilia function. Additionally, 3D culture histology revealed striking ependymal rosette formation, similar to primary tumors. Transcriptional enrichment of extracellular matrix, however, was a common signature of EPN primary tumor and cell lines in both monolayer and 3D formats.

2016-09-09 | GSE86574 | GEO

TDP-43 Neurotoxicity in late D. melanogaster pupae

Project description:The aim of this study is to understand the mechanisms of TDP-43 neurotoxicity. Here, we perform a RNA-Seq analysis in TDP-43 gain-of-fucntion (GOF) , TDP-43 loss-of-function and wild-type late pupae heads (73-90 hours APF) and perform TDP-43 GOF vs wild type and TDP-43 LOF vs wild-type differential expression analysis to show that both mechanisms presents defects in ecdysone receptor (ECR)-dependeint transcriptional program switching, and strongly deregulate expression from the neuronal microtubule associated protien Map205. RNA-seq was performed in two wild-type D.melanogaster biological replicates (Canton S, w1118 ), four biological replicates for TDP-43 (LOF) with two distinct genotypes (dTDP-43Δ142/Df(2R)106,dTDP-43Δ23/Δ142 ) and two TDP-43 GOF biological replicates (act5c>dTDP-43 ).

2013-01-22 | E-GEOD-42844 | biostudies-arrayexpress

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