Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Genomic, transcriptomic and epigenomic profiling of GCTB

ABSTRACT: Giant cell tumor of bone is a rare bone neoplasm driven by oncogenic hotspot G34W/L/V mutations in the non-canonical histone variant H3.3. This study provides primary data of genomic (WGS), transcriptomic (RNA-seq) and epigenomic (histone mark ChIP-seq, WGBS, ATAC-seq) profiling of primary GCTB samples from several cohorts in Germany and Korea. We confirm the H3.3-G34 mutations as sole genetic drivers of GCTB, and describe the epigenetic alterations in mutant GCTB stromal cells.

PROVIDER: EGAS00001003730 | EGA |

REPOSITORIES: EGA

ACCESS DATA

Json Xml

Similar Datasets

H3.3G34W promotes growth and impedes differentiation of osteoblast-like mesenchymal progenitors in Giant Cell Tumour of Bone [RNA-Seq]

Project description:Glycine 34 to tryptophan (G34W) substitutions in H3.3 arise in ~90% of giant cell tumour of bone (GCT). Here, we show H3.3G34W is necessary for tumour formation. Profiling the epigenome, transcriptome and secreted proteome of patient samples and tumour-derived cells CRISPR/Cas9-edited for H3.3G34W shows that H3.3K36me3 loss on mutant H3.3 induces a shift of the repressive H3K27me3 mark from intergenic to genic regions, beyond areas of H3.3 deposition. This promotes the redistribution of antagonistic chromatin marks and aberrant downregulation of contractile myofibroblast-associated genes altering cell fate in mesenchymal progenitors. Single-cell transcriptomics reveals that H3.3G34W stromal cells recapitulate a neoplastic trajectory from an SPP1+ osteoblast progenitor-like population towards an ACTA2+ myofibroblast population, which secretes extracellular matrix ligands predicted to recruit and activate osteoclasts. Our findings suggest that H3.3G34W leads to GCT by sustaining a transformed state in osteoblast-like progenitors which promotes neoplastic growth, pathological recruitment of giant osteoclasts, and bone destruction.

2020-10-01 | GSE149209 | GEO

H3.3G34W promotes growth and impedes differentiation of osteoblast-like mesenchymal progenitors in giant cell tumour of bone [scRNA-Seq and snRNA-Seq]

2020-10-01 | GSE149201 | GEO

H3.3G34W promotes growth and impedes differentiation of osteoblast-like mesenchymal progenitors in Giant Cell Tumour of Bone [ChIP-Seq]

2020-10-01 | GSE149198 | GEO

Gene expression data of pHGG tumor samples

2014-05-14 | GSE49822 | GEO

4ec20a21-6fd0-4e08-bc35-6ec503ead02d - samples

Project description:This dataset contains primary raw data of whole-genome sequencing, whole-genome bisulfite sequencing, ATAC-seq, ChIP-seq (ChIP-mentation) of histone variants and modifications, as well as RNA-seq of giant cell tumor of bone tissue and primary cell line samples.

| EGAD00001005109 | EGA

Gene expression data of pHGG tumor samples

Project description:Pediatric high-grade gliomas (pHGGs) harboring the K27M mutation of H3F3A (histone H3.3) are characterized by global reduction of the repressive histone mark H3K27me3 and DNA hypomethylation. Analysis of K27M-induced changes on H3K27me3 occupancy and DNA methylation at differentially expresed genes (K27M vs. wild-type H3.3) in primary pHGG tumor samples. 22 glioblastoma samples from pHGG patients were selected for RNA extraction and hybridization on Affymetrix Affymetrix Human Genome U133 Plus 2.0 Arrays. Expression profiling data of 17 pHHGs are part of our previous study (GSE36245 or GSE34824).

2014-05-14 | E-GEOD-49822 | biostudies-arrayexpress

Histone H3.3 is required for endogenous retroviral element silencing and genome stability [RNA-Seq]

Project description:Endogenous retroviruses (ERVs) have provided an evolutionary advantage in the diversification of transcript regulation and are thought to be involved in the establishment of extraembryonic tissues during development. However, silencing of these elements remains critical for the maintenance of genome stability. Here, we define a new chromatin state that is uniquely characterized by the combination of the histone variant H3.3 and H3K9me3, two chromatin ‘marks’ that have previously been considered to belong to fundamentally opposing chromatin states. H3.3/H3K9me3 heterochromatin is fundamentally distinct from ‘canonical’ H3K9me3 heterochromatin that has been under study for decades and this unique functional interplay of a histone variant and a repressive histone mark is crucial for silencing ERVs in ESCs. Our study solidifies the emerging notion that H3.3 is not a histone variant associated exclusively with “active” chromatin and further suggests that its incorporation at unique heterochromatic regions may be central to its function during development and the maintenance of genome stability. RNA-seq analysis of three embryonic stem cell lines WT, H3.3 KO1, and H3.3 KO2)

2015-05-05 | E-GEOD-59104 | biostudies-arrayexpress

ChIP-sequencing of high grade glioma (HGG) mouse cells encoding for H3.3-G34R vs H3.3-WT histones, derived from a Sleeping beauty based-genetically engineered mouse model.

Project description:ChIP-sequencing of H3.3-G34R and H3.3-WT HGG cells was performed for several histone marks to uncover differences on histone mark deposition related to the presence of H3.3-G34R mutation, using a Sleeping beauty derived genetically engenieered mouse model.

2020-11-16 | GSE161503 | GEO

The histone variant H3.3 G34W substitution in giant cell tumor of the bone link chromatin and RNA processing [RNA-seq]

Project description:While transcription as regulated by histones and their post-translational modifications have been well described, the connection between histone variants and changes to transcription remains poorly characterized. Potentially important insight into this process is provided by the frequently occurring mutations of H3.3, leading to G34 substitutions in childhood glioblastoma and giant cell tumor of the bone (GCTB). In this study, we have established primary cell lines from GCTB patients and used them to uncover the influence on cellular growth behavior, gene expression, and chromatin compaction. The primary cells with G34W show increased colony formation, infiltration and proliferation, hallmarks in aggressive tumor development. Isogenic cell lines with G34W recapitulated the increased proliferation observed in primary cells. Transcriptomic analysis of primary cells and biopsies suggest that most genes are downregulated, which is also reflected in increased chromatin compaction. We identified components of the spliceosome complex specifically interacting with G34W in established isogenic cell lines with a GFP-tagged H3.3. RNA-sequencing analysis and hybridization-based validations further enforced splicing aberrations. Our data uncover a role in RNA processing and chromatin modulation that is blocked by G34W, potentially driving the tumorigenic process in GCTB.

2017-10-18 | GSE103559 | GEO

The histone variant H3.3 G34W substitution in giant cell tumor of the bone link chromatin and RNA processing

2017-10-18 | GSE102193 | GEO