Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Single cell multi-omic study of H3-K27M mutant diffuse midline glioma across age and location

ABSTRACT: Histone 3 lysine27-to-methionine (H3-K27M) mutations most frequently occur in childhood diffuse midline gliomas (DMGs) of the pons, but are also increasingly recognized in adult DMGs. Their potential heterogeneity at different ages and midline locations are vastly understudied. Here, through dissecting the single-cell transcriptomic, epigenomic and spatial architectures of a comprehensive cohort of patient H3-K27M DMGs, we delineate how age and anatomical location shape glioma cell-intrinsic and -extrinsic features in light of the shared driver mutation. We conducted multi-omic profiling of 50 H3-K27M mutant patient tumors. We performed deep full-length Smart-seq2 fresh single-cell (n=18) or frozen single-nucleus (n=25) RNA-sequencing (sc/snRNA-seq) of 43 tumors). We additionally analyzed the open chromatin profiles of 8 tumors utilizing the single-cell/nucleus assay for transposase-accessible chromatin using sequencing (snATAC-seq)

PROVIDER: EGAS00001006994 | EGA |

REPOSITORIES: EGA

ACCESS DATA

Json Xml

Similar Datasets

Single cell epigenomic study of H3-K27M mutant diffuse midline glioma across age and location

Project description:Histone 3 lysine27-to-methionine (H3-K27M) mutations most frequently occur in childhood diffuse midline gliomas (DMGs) of the pons, but are also increasingly recognized in adult DMGs. Their potential heterogeneity at different ages and midline locations are vastly understudied. Here, through dissecting the single-cell epigenomic architectures of a comprehensive cohort of patient H3-K27M DMGs, we delineate how age and anatomical location shape glioma cell-intrinsic and -extrinsic features in light of the shared driver mutation. We analyzed the open chromatin profiles of 8 tumors utilizing the single-cell/nucleus assay for transposase-accessible chromatin using sequencing (snATAC-seq)

| EGAS00001007035 | EGA

Histone H3 wild-type DIPG/DMG overexpressing EZHIP extend the spectrum diffuse midline gliomas with PRC2 inhibition beyond H3-K27M mutation

Project description:Characterisation of a new subgroup of DMG lacking H3-K27M mutation that is defined by H3K27me3 loss and EZHIP overexpression that can be detected by IHC. These tumors are distinct from EZHIP-positive posterior fossa ependymomas and are associated with a dismal prognosis. We propose that these EZHIP/H3-WT tumors need to be considered similar to canonical DIPG/DMG, thus extending the spectrum of DMG with PRC2 inhibition beyond H3-K27M mutation

2020-03-20 | E-MTAB-8888 | biostudies-arrayexpress

Whole exome-sequencing of pediatric and adult H3-K27M diffuse midline glioma

Project description:H3-K27M mutant difffuse midline gliomas across different age groups and anatomical locations were profiled by WES.

| EGAS00001006431 | EGA

Mutations within FGFR1 and BRAF indicate superior outcome in diffuse midline gliomas, H3F3A K27M mutant

Project description:Diffuse midline glioma (DMG) is a devastating disease that is defined by its localization, by the diffuse growth of astrocytic tumor cells, and by K27M mutations within Histone H3 proteins. In a large series of such tumor samples (n=83), we show here that 12 % of these cases (n=10) harbor concomitant hotspot mutations within FGFR1 or BRAF. Respective cases were all located in midline structures and matched with reference cases of DMG using global DNA methylation profiling. TP53 mutations were significantly more frequent in BRAF/FGFR1 wild type cases. Presence of hotspot mutations within FGFR1 or BRAF was associated with a significantly better overall survival, which was independent of the patients’ age and tumor localization. Thus, our results establish the relevance of FGFR1 or BRAF mutations in DMG as a prognostic marker and open new targeted therapy options in this subgroup of DMG.

2020-12-08 | GSE161944 | GEO

H3 K27M and EZHIP impede H3K27-methylation spreading by inhibing allosterically stimulated PRC2 [K27M]

Project description:In this study, we report that EZHIP and H3 K27M preferentially interact with an allosterically activated form of PRC2 in vivo. The formation of H3 K27M- and EZHIP-PRC2 complexes occurs at CpG islands containing H3K27me3 and impedes PRC2 and H3K27me3 spreading. Moreover, we find that H3 K27M inhibits PRC2 in trans and can reduce H3K27me3 levels independent of chromatin incorporation. While EZHIP is not found outside of placental mammals, we find that expression of human EZHIP reduces H3K27me3 in Drosophila melanogaster through a conserved molecular mechanism.

2020-10-12 | GSE151980 | GEO

5597e873-4b97-494f-8ca6-3ba129a345d5 - samples

Project description:This dataset contains the open chromatin profiles of 8 patient H3-K27M mutant DMGs utilizing the single-cell/nucleus assay for transposase-accessible chromatin using sequencing (snATAC-seq)

| EGAD00001010170 | EGA

Dual interactions of K27M mutant nucleosomes with PRC2 and MLL1 shape the cancer epigenetic landscape (ATAC-seq)

Project description:Cancer associated mutations in genes encoding histones dramatically reshape chromatin patterns and support tumorigenesis, despite their low prevalence. Lysine to Methionine substitution of residue 27 on histone H3 (K27M) is a driver mutation in high-grade pediatric gliomas, known to abrogate Polycomb activity. We applied single-molecule systems to image individual nucleosomes and delineate the combinatorial chromatin patterns associated with K27M expression. We find that K27M-mutant nucleosomes not only sequester PRC2, but also bind preferentially to MLL1, thus leading to genome-wide redistribution of H3K4me3. K27M-mediated deregulation of both repressive and activating chromatin marks maintains ‘bivalent’ chromatin, supporting a poorly differentiated cellular state. This study provides evidence for widespread effects of the K27M oncohistone on multiple core epigenetic pathways, and highlights the use of single-molecule tools to reveal mechanisms of chromatin deregulation in cacner.

2022-05-15 | GSE163182 | GEO

Dual interactions of K27M mutant nucleosomes with PRC2 and MLL1 shape the cancer epigenetic landscape (Cut&Run)

2022-05-15 | GSE158447 | GEO

Dual interactions of K27M mutant nucleosomes with PRC2 and MLL1 shape the cancer epigenetic landscape (MARS-seq)

2022-05-15 | GSE163183 | GEO

Single cell multi-omics profiling of H3-K27M DMG

Project description:Multi-omics profiling of H3-K27M DMGs across different age groups and locations, using fresh single whole cell RNA-seq, scATACseq, spatial in situ sequencing, and WES/targeted exome sequencing.

2022-08-09 | GSE184357 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data