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Sox9 directs divergent epigenomic states in brain tumor subtypes

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

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE202961 | GEO | 2022/05/20

REPOSITORIES: GEO

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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

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 (ChIP-Seq)

Project description: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.

2022-05-20 | GSE202960 | GEO

Sox9 directs divergent epigenomic states in brain tumor subtypes

Project description:Sox9 directs divergent epigenomic states in brain tumor subtypes

| PRJNA837883 | ENA

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

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

| PRJNA837888 | ENA

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

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

| PRJNA837891 | ENA

Divergent genomic and epigenomic landscapes of lung cancer subtypes underscore the selection of different oncogenic pathways during tumor development.

Project description:For therapeutic purposes, non-small cell lung cancer (NSCLC) has traditionally been regarded as a single disease. However, recent evidence suggest that the two major subtypes of NSCLC, adenocarcinoma (AC) and squamous cell carcinoma (SqCC) respond differently to both molecular targeted and new generation chemotherapies. Therefore, identifying the molecular differences between these tumor types may impact novel treatment strategy. We performed the first large-scale analysis of 261 primary NSCLC tumors (169 AC and 92 SqCC), integrating genome-wide DNA copy number, methylation and gene expression profiles to identify subtype-specific molecular alterations relevant to new agent design and choice of therapy. Comparison of AC and SqCC genomic and epigenomic landscapes revealed 778 altered genes with corresponding expression changes that are selected during tumor development in a subtype-specific manner. Analysis of >200 additional NSCLCs confirmed that these genes are responsible for driving the differential development and resulting phenotypes of AC and SqCC. Importantly, we identified key oncogenic pathways disrupted in each subtype that likely serve as the basis for their differential tumor biology and clinical outcomes. Downregulation of HNF4? target genes was the most common pathway specific to AC, while SqCC demonstrated disruption of numerous histone modifying enzymes as well as the transcription factor E2F1. In silico screening of candidate therapeutic compounds using subtype-specific pathway components identified HDAC and PI3K inhibitors as potential treatments tailored to lung SqCC. Together, our findings suggest that AC and SqCC develop through distinct pathogenetic pathways that have significant implication in our approach to the clinical management of NSCLC.

| S-EPMC3357406 | biostudies-literature

Epigenomic tensor predicts disease subtypes and reveals constrained tumor evolution.

Project description:Understanding the epigenomic evolution and specificity of disease subtypes from complex patient data remains a major biomedical problem. We here present DeCET (decomposition and classification of epigenomic tensors), an integrative computational approach for simultaneously analyzing hierarchical heterogeneous data, to identify robust epigenomic differences among tissue types, differentiation states, and disease subtypes. Applying DeCET to our own data from 21 uterine benign tumor (leiomyoma) patients identifies distinct epigenomic features discriminating normal myometrium and leiomyoma subtypes. Leiomyomas possess preponderant alterations in distal enhancers and long-range histone modifications confined to chromatin contact domains that constrain the evolution of pathological epigenomes. Moreover, we demonstrate the power and advantage of DeCET on multiple publicly available epigenomic datasets representing different cancers and cellular states. Epigenomic features extracted by DeCET can thus help improve our understanding of disease states, cellular development, and differentiation, thereby facilitating future therapeutic, diagnostic, and prognostic strategies.

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BRD4 directs glycolytic metabolism through a comprehensive epigenomic and transcriptional network

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

2018-03-31 | GSE59162 | GEO

Epigenomic comparison of distinct pluripotent stem cell states reveals a new class of enhancers with roles throughout mammalian development

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

2014-06-04 | E-GEOD-57409 | biostudies-arrayexpress