Ontology highlight
ABSTRACT:
PROVIDER: PRJNA116143 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:This SuperSeries is composed of the following subset Series: GSE16581: Genomic landscape of meningiomas: gene expression GSE16583: Genomic landscape of meningiomas: genotyping Refer to individual Series
2010-12-01 | E-GEOD-16584 | biostudies-arrayexpress
Project description:Genomic landscape of meningiomas: gene expression
| PRJNA122763 | ENA
Project description:Meningiomas represent one of the most common and clinically heterogeneous brain tumor types that only modestly correlate with histopathologic features. While emerging molecular profiling efforts have linked specific genomic drivers to distinct clinical patterns, the proteomic landscape of meningiomas remains largely unexplored. We utilize mass spectrometry to profile a clinically well-annotated cohort (n=69) of meningiomas stratified to span all three World Health Organization (WHO) grades and various degrees of clinical aggressiveness. In total, we quantify 3042 unique proteins and compare the patterns across different clinical parameters. Unsupervised clustering analysis highlighted distinct proteomic (n=106 proteins, Welch’s t-test, P<0.01) and pathway-level (e.g. Notch and PI3K/AKT/mTOR) differences between convexity and skull base meningiomas. Supervised comparative analyses of different pathological grades revealed distinct patterns between benign (WHO Grade I) and atypical/malignant (WHO Grade II and III) meningiomas with classic oncogenes often enriched in higher grade lesions. Independent of WHO grade, clinically aggressive meningiomas, that rapidly recurred, also had distinctive protein patterns that converged on mRNA processing and impaired activation of the extracellular matrix naba matrisome complex. Larger sized meningiomas, and those with previous radiation exposure, also had distinct protein profiles. Collectively, we highlight distinct clinically-dependent proteomic patterns of meningiomas that may help better predict outcome and guide the development of more personalized and directed therapies.
2019-05-30 | PXD012923 | Pride
Project description:Meningiomas are mostly benign brain tumors, with a potential for becoming atypical or malignant. Based on comprehensive genomic, transcriptomic and epigenomic analyses of meningiomas, we compared benign tumors to atypical ones. We show that the vast majority of primary (de novo) atypical meningiomas display loss of NF2, which co-occurs either with genomic instability or recurrent mutations in SMARCB1. These tumors harbor increased H3K27me3 repressive signal and a hypermethylated phenotype, mainly occupying the polycomb repressive complex 2 (PRC2) binding sites in human embryonic stem cells (hESCs), thereby phenocopying a more primitive cellular state. Consistent with this observation, and based on differential gene expression analysis as well as correlation of mRNA:miRNA regulatory networks, atypical meningiomas exhibit up-regulation of EZH2, the catalytic subunit of the PRC2 complex, well as the E2F2 and FOXM1 transcriptional networks that promote proliferation through activation of the cell cycle pathways. In addition, based on H3K27ac ChIP-seq analysis, we show atypical tumors to display an activated super-enhancer near the meningeal identity transcription factor ZIC1, leading to its transcriptional upregulation. Importantly, these primary atypical meningiomas do not harbor activating TERT promoter mutations, which have been reported in atypical tumors that progressed from benign ones. Our results establish the genomic landscape of primary atypical meningiomas, differentiating their profile from benign and progressed tumors and establishing novel therapeutic targets.
2016-12-20 | GSE92558 | GEO
Project description:Meningiomas are mostly benign brain tumors, with a potential for becoming atypical or malignant. Based on comprehensive genomic, transcriptomic and epigenomic analyses of meningiomas, we compared benign tumors to atypical ones. We show that the vast majority of primary (de novo atypical meningiomas display loss of NF2, which co-occurs either with genomic instability or recurrent mutations in SMARCB1. These tumors harbor increased H3K27me3 repressive signal and a hypermethylated phenotype, mainly occupying the polycomb repressive complex 2 (PRC2 binding sites in human embryonic stem cells (hESCs, thereby phenocopying a more primitive cellular state. Consistent with this observation, and based on differential gene expression analysis as well as correlation of mRNA:miRNA regulatory networks, atypical meningiomas exhibit up-regulation of EZH2, the catalytic subunit of the PRC2 complex, well as the E2F2 and FOXM1 transcriptional networks that promote proliferation through activation of the cell cycle pathways. In addition, based on H3K27ac ChIP-seq analysis, we show atypical tumors to display an activated super-enhancer near the meningeal identity transcription factor ZIC1, leading to its transcriptional upregulation. Importantly, these primary atypical meningiomas do not harbor activating TERT promoter mutations, which have been reported in atypical tumors that progressed from benign ones. Our results establish the genomic landscape of primary atypical meningiomas, differentiating their profile from benign and progressed tumors and establishing novel therapeutic targets.
2017-01-12 | GSE93519 | GEO
Project description:Meningiomas are one of the most common adult brain tumors. For most patients, surgical excision is curative. However, up to 20% recur. Currently, the molecular determinants predicting recurrence and malignant transformation are lacking. We performed global genetic and genomic analysis of 85 meningioma samples of various grades. Copy number alterations were assessed by 100K SNP arrays and correlated with gene expression, proliferation indices, and clinical outcome. In addition to chromosome 22q loss, which was detected in the majority of clinical samples, chromosome 18q and 6q loss significantly predicted recurrence and was associated with anaplastic histology. Five "classes" of meningiomas were detected by gene expression analysis that correlated with copy number alterations, recurrence risk, and malignant histology. These classes more accurately predicted tumor recurrence than Ki-67 index, the gold standard for determining risk of recurrence, and highlight substantial expression heterogeneity between meningiomas. These data offer the most complete description of the genomic landscape of meningiomas and provide a set of tools that could be used to more accurately stratify meningioma patients into prognostic risk groups.
2011-10-12 | GSE16583 | GEO
Project description:Meningiomas are mostly benign brain tumors, with a potential for becoming atypical or malignant. Based on comprehensive genomic, transcriptomic and epigenomic analyses of meningiomas, we compared benign tumors to atypical ones. We show that the vast majority of primary (de novo) atypical meningiomas display loss of NF2, which co-occurs either with genomic instability or recurrent mutations in SMARCB1. These tumors harbor increased H3K27me3 repressive signal and a hypermethylated phenotype, mainly occupying the polycomb repressive complex 2 (PRC2) binding sites in human embryonic stem cells (hESCs), thereby phenocopying a more primitive cellular state. Consistent with this observation, and based on differential gene expression analysis as well as correlation of mRNA:miRNA regulatory networks, atypical meningiomas exhibit up-regulation of EZH2, the catalytic subunit of the PRC2 complex, well as the E2F2 and FOXM1 transcriptional networks that promote proliferation through activation of the cell cycle pathways. In addition, based on H3K27ac ChIP-seq analysis, we show atypical tumors to display an activated super-enhancer near the meningeal identity transcription factor ZIC1, leading to its transcriptional upregulation. Importantly, these primary atypical meningiomas do not harbor activating TERT promoter mutations, which have been reported in atypical tumors that progressed from benign ones. Our results establish the genomic landscape of primary atypical meningiomas, differentiating their profile from benign and progressed tumors and establishing novel therapeutic targets.
2016-12-20 | GSE91375 | GEO
Project description:Meningiomas are one of the most common adult brain tumors. For most patients, surgical excision is curative. However, up to 20% recur. Currently, the molecular determinants predicting recurrence and malignant transformation are lacking. We performed global genetic and genomic analysis of 85 meningioma samples of various grades. Copy number alterations were assessed by 100K SNP arrays and correlated with gene expression, proliferation indices, and clinical outcome. In addition to chromosome 22q loss, which was detected in the majority of clinical samples, chromosome 18q and 6q loss significantly predicted recurrence and was associated with anaplastic histology. Five classes of meningiomas were detected by gene expression analysis that correlated with copy number alterations, recurrence risk, and malignant histology. These classes more accurately predicted tumor recurrence than Ki-67 index, the gold standard for determining risk of recurrence, and highlight substantial expression heterogeneity between meningiomas. These data offer the most complete description of the genomic landscape of meningiomas and provide a set of tools that could be used to more accurately stratify meningioma patients into prognostic risk groups.
2010-11-30 | GSE16581 | GEO
Project description:Meningiomas are one of the most common adult brain tumors. For most patients, surgical excision is curative. However, up to 20% recur. Currently, the molecular determinants predicting recurrence and malignant transformation are lacking. We performed global genetic and genomic analysis of 85 meningioma samples of various grades. Copy number alterations were assessed by 100K SNP arrays and correlated with gene expression, proliferation indices, and clinical outcome. In addition to chromosome 22q loss, which was detected in the majority of clinical samples, chromosome 18q and 6q loss significantly predicted recurrence and was associated with anaplastic histology. Five classes of meningiomas were detected by gene expression analysis that correlated with copy number alterations, recurrence risk, and malignant histology. These classes more accurately predicted tumor recurrence than Ki-67 index, the gold standard for determining risk of recurrence, and highlight substantial expression heterogeneity between meningiomas. These data offer the most complete description of the genomic landscape of meningiomas and provide a set of tools that could be used to more accurately stratify meningioma patients into prognostic risk groups. Tumor biopsies from 43 female and 25 male subjects with sporadic meningioma were identified from the UCLA Neuro-oncology Program Tissue Bank through institutional review board approved protocols. 43 tumors were designated "benign" WHO I, 19 tumors were "atypical" WHO II, and 6 were "anaplastic" WHO III. Gene expression analysis was performed on the 68 tumor biopsies.
2010-11-30 | E-GEOD-16581 | biostudies-arrayexpress