3D genome topology distinguishes molecular subgroups of medulloblastoma
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ABSTRACT:
PROVIDER: PRJNA1031604 | ENA |
REPOSITORIES: ENA
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Project description:Four main medulloblastoma (MB) molecular subtypes have been identified based on transcriptional, DNA methylation and genetic profiles. However, it is currently not known whether MB subtypes have their own specific 3D genome architecture. Hi-C maps were globally stable across MB subtypes. However, among the 3D genome features we tested, boundary strengths of topologically associating domains (TADs) were the best at classifying MB samples – including Group 3 and Group 4 specimens - according to their known molecular subtypes. Although boundary strength was not generally associated with differential gene expression between subtypes, we found that Group 3 and Group 4 specimens had differential TAD boundary strengths near genes that are uniquely expressed in their respective lineages of origin. Accordingly, we provide examples of TAD boundary reorganization that clearly distinguish Group 3 and 4 samples at these developmentally important genomic sites. TAD boundary strength allows classification of MB molecular subtypes, indicating that the shape of the 3D genome is unique to each molecular subtype. Genome topologies of Group 3 and 4 tumors are shaped differently at key lineage genes, but these differences are not strongly predictive of changes in gene expression. 3D genome architecture might be a fossil of the lineages of origin of MB subtypes.
2024-09-29 | GSE246125 | GEO
Project description:Proteogenomic landscape of medulloblastoma subgroups
| PRJNA420382 | ENA
Project description:Extensive high-throughput sequencing led to the characterization of four main medulloblastoma subgroups. However, to date these analyses have not attained a global comprehension of their dynamic network complexity. Wishing to get a comprehensive view of all medulloblastoma subgroups, we employed a proteomic analysis to integrate accurate protein activity. In this study we present the first analysis regrouping genomic and methylation status, whole-transcriptome sequencing and quantitative proteomics. First, our proteomic analysis clarified medulloblastoma subgroup identity. Second, analysis of proteome and phosphoproteome highlighted disregulated signalling pathways that have not been predicted by transcriptomic analysis. Altogether, combined multi-scale analyses of medulloblastoma have allowed us to identify and prioritize novel molecular drivers involved in human medulloblastoma.
2018-09-09 | GSE107508 | GEO
Project description:Extensive high-throughput sequencing led to the characterization of four main medulloblastoma subgroups. However, to date these analyses have not attained a global comprehension of their dynamic network complexity. Wishing to get a comprehensive view of all medulloblastoma subgroups, we employed a proteomic analysis to integrate accurate protein activity. In this study we present the first analysis regrouping genomic and methylation status, whole-transcriptome sequencing and quantitative proteomics. First, our proteomic analysis clarified medulloblastoma subgroup identity. Second, analysis of proteome and phosphoproteome highlighted disregulated signalling pathways that have not been predicted by transcriptomic analysis. Altogether, combined multi-scale analyses of medulloblastoma have allowed us to identify and prioritize novel molecular drivers involved in human medulloblastoma.
2018-09-09 | GSE104728 | GEO
Project description:Medulloblastoma is a malignant childhood brain tumour comprising four discrete subgroups. To identify mutations that drive medulloblastoma we sequenced the entire genomes of 37 tumours and matched normal blood. One hundred and thirty-six genes harbouring somatic mutations in this discovery set were sequenced in an additional 56 medulloblastomas. Recurrent mutations were detected in 41 genes not yet implicated in medulloblastoma: several target distinct components of the epigenetic machinery in different disease subgroups, e.g., regulators of H3K27 and H3K4 trimethylation in subgroup-3 and 4 (e.g., KDM6A and ZMYM3), and CTNNB1-associated chromatin remodellers in WNT-subgroup tumours (e.g., SMARCA4 and CREBBP). Modelling of mutations in mouse lower rhombic lip progenitors that generate WNT-subgroup tumours, identified genes that maintain this cell lineage (DDX3X) as well as mutated genes that initiate (CDH1) or cooperate (PIK3CA) in tumourigenesis. These data provide important new insights into the pathogenesis of medulloblastoma subgroups and highlight targets for therapeutic development. A total of 76 pediatric medulloblastoma samples were analyzed, representing 4 expression classes
2012-07-05 | E-GEOD-37418 | biostudies-arrayexpress
Project description:Proteogenomic landscape of medulloblastoma subgroups [methylation]
| PRJNA413673 | ENA
Project description:Proteogenomic landscape of medulloblastoma subgroups [SNP]
| PRJNA420381 | ENA
Project description:Medulloblastoma is a malignant childhood brain tumour comprising four discrete subgroups. To identify mutations that drive medulloblastoma we sequenced the entire genomes of 37 tumours and matched normal blood. One hundred and thirty-six genes harbouring somatic mutations in this discovery set were sequenced in an additional 56 medulloblastomas. Recurrent mutations were detected in 41 genes not yet implicated in medulloblastoma: several target distinct components of the epigenetic machinery in different disease subgroups, e.g., regulators of H3K27 and H3K4 trimethylation in subgroup-3 and 4 (e.g., KDM6A and ZMYM3), and CTNNB1-associated chromatin remodellers in WNT-subgroup tumours (e.g., SMARCA4 and CREBBP). Modelling of mutations in mouse lower rhombic lip progenitors that generate WNT-subgroup tumours, identified genes that maintain this cell lineage (DDX3X) as well as mutated genes that initiate (CDH1) or cooperate (PIK3CA) in tumourigenesis. These data provide important new insights into the pathogenesis of medulloblastoma subgroups and highlight targets for therapeutic development.
2012-07-06 | GSE37418 | GEO
Project description:Two medulloblastoma cell lines (ONS-76 and HDMB-03) were grown in 3D hyaluronan hydrogels for three weeks. We observed nodules forming showing different behavior and wanted to evaluate if these different nodules (slow vs fast vs non-growing, migrating and invading cells) are also characterised by different gene expression patterns. We performed this experiment on a SHH (ONS-76) and on a group 3 MB (HDMB-03) cell line to compare if certain subpopulations would be unique for the subgroups.
2023-02-23 | E-MTAB-12591 | biostudies-arrayexpress
Project description:Medulloblastoma in adults: Cytogenetic phenotypes identify prognostic subgroups
| PRJNA704366 | ENA