899e7d94-7491-4f3a-9380-2f8754b84579 - samples
Ontology highlight
ABSTRACT:
PROVIDER: EGAD00001011339 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:Fastq or bam files are deposited for 28 patient H3-K27M diffuse midline gliomas. UMPEDD65 was profiled by targeted exome-sequencing using the TSO500 Illumina assay, while all other samples were sequenced by whole-exome sequencing.
| EGAD00001009269 | EGA
Project description:It is not known whether midline pediatric gliomas driven by Histone 3 K27M mutations (oncohistones) or EZHIP expression (oncohistone-mimics) share a common cell-of-origin, or arise from distinct cell types with unique vulnerabilities to PRC2 inhibition and partner alterations. Here, we define the etiological and oncogenic relationship between pediatric midline gliomas characterized by inhibition of K27M and K27M-like oncohistones. We assemble an extensive reference for gliogenesis from the developing mouse and human fetal brain. With bulk and single-cell transcriptomics and epigenomics, we profiled a large cohort of primary tumors comprising H3.1K27M and H3.3K27M pontine gliomas, H3.3K27M thalamic gliomas, and EZHIP+ posterior fossa ependymomas. We focus on differences across axes of location (thalamus vs. pons vs. posterior fossa), tumor type (diffuse midline gliomas vs. ependymomas), and oncohistone (H3.1/2K27M vs. H3.3K27M vs. EZHIP). We use tumor molecular features to delineate transcriptional states and cell-of-origin in each entity. Finally, we use culture models in isogenic contexts to interrogate the effect of each oncohistone or mimic.
2022-06-27 | GSE188625 | GEO
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 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)
| EGAS00001006994 | EGA
Project description:H3-K27M mutant difffuse midline gliomas across different age groups and anatomical locations were profiled by WES.
| EGAS00001006431 | EGA
Project description:Diffuse midline gliomas (DMGs) are uniformly fatal pediatric central nervous system cancers, refractory to standard of care therapeutic modalities. The primary genetic drivers are a set of recurrent amino acid substitutions in genes encoding histone H3 (H3.3 and H3.1, K27M), which are currently undruggable. These H3K27M oncohistones perturb normal chromatin architecture, resulting in an aberrant epigenetic landscape, which we interrogated here for epigenetic dependencies using a CRISPR screen in patient-derived H3K27M-glioma neurospheres. We show that H3K27M-glioma cells are dependent on core components of the mammalian SWI/SNF (BAF) chromatin remodeling complex for maintaining glioma stem cells in a cycling, oligodendrocyte precursor cell (OPC)-like state. Genetic perturbation of the BAF catalytic subunit SMARCA4 (BRG1), as well as pharmacological suppression opposes proliferation, promotes differentiation, and improves overall survival of patient-derived xenograft (PDX) models. In summary, we demonstrate that therapeutic inhibition of BAF complex has translational potential for children with H3K27M-gliomas.
2022-09-15 | GSE212782 | GEO
Project description:Diffuse midline gliomas (DMGs) are uniformly fatal pediatric central nervous system cancers, refractory to standard of care therapeutic modalities. The primary genetic drivers are a set of recurrent amino acid substitutions in genes encoding histone H3 (H3.3 and H3.1, K27M), which are currently undruggable. These H3K27M oncohistones perturb normal chromatin architecture, resulting in an aberrant epigenetic landscape, which we interrogated here for epigenetic dependencies using a CRISPR screen in patient-derived H3K27M-glioma neurospheres. We show that H3K27M-glioma cells are dependent on core components of the mammalian SWI/SNF (BAF) chromatin remodeling complex for maintaining glioma stem cells in a cycling, oligodendrocyte precursor cell (OPC)-like state. Genetic perturbation of the BAF catalytic subunit SMARCA4 (BRG1), as well as pharmacological suppression opposes proliferation, promotes differentiation, and improves overall survival of patient-derived xenograft (PDX) models. In summary, we demonstrate that therapeutic inhibition of BAF complex has translational potential for children with H3K27M-gliomas.
2022-09-15 | GSE212679 | GEO
Project description:Diffuse midline gliomas (DMGs) are uniformly fatal pediatric central nervous system cancers, refractory to standard of care therapeutic modalities. The primary genetic drivers are a set of recurrent amino acid substitutions in genes encoding histone H3 (H3.3 and H3.1, K27M), which are currently undruggable. These H3K27M oncohistones perturb normal chromatin architecture, resulting in an aberrant epigenetic landscape, which we interrogated here for epigenetic dependencies using a CRISPR screen in patient-derived H3K27M-glioma neurospheres. We show that H3K27M-glioma cells are dependent on core components of the mammalian SWI/SNF (BAF) chromatin remodeling complex for maintaining glioma stem cells in a cycling, oligodendrocyte precursor cell (OPC)-like state. Genetic perturbation of the BAF catalytic subunit SMARCA4 (BRG1), as well as pharmacological suppression opposes proliferation, promotes differentiation, and improves overall survival of patient-derived xenograft (PDX) models. In summary, we demonstrate that therapeutic inhibition of BAF complex has translational potential for children with H3K27M-gliomas.
2022-09-15 | GSE212700 | GEO
Project description:Diffuse midline gliomas (DMGs) are uniformly fatal pediatric central nervous system cancers, refractory to standard of care therapeutic modalities. The primary genetic drivers are a set of recurrent amino acid substitutions in genes encoding histone H3 (H3.3 and H3.1, K27M), which are currently undruggable. These H3K27M oncohistones perturb normal chromatin architecture, resulting in an aberrant epigenetic landscape, which we interrogated here for epigenetic dependencies using a CRISPR screen in patient-derived H3K27M-glioma neurospheres. We show that H3K27M-glioma cells are dependent on core components of the mammalian SWI/SNF (BAF) chromatin remodeling complex for maintaining glioma stem cells in a cycling, oligodendrocyte precursor cell (OPC)-like state. Genetic perturbation of the BAF catalytic subunit SMARCA4 (BRG1), as well as pharmacological suppression opposes proliferation, promotes differentiation, and improves overall survival of patient-derived xenograft (PDX) models. In summary, we demonstrate that therapeutic inhibition of BAF complex has translational potential for children with H3K27M-gliomas.
2022-09-15 | GSE212718 | GEO
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
Project description:Mutations within FGFR1 and BRAF indicate superior outcome in diffuse midline gliomas, H3F3A K27M mutant
| PRJNA679958 | ENA