D1a44105-ab8a-48d2-b730-d22748c3597a - samples
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ABSTRACT:
PROVIDER: EGAD00001009391 | EGA |
REPOSITORIES: EGA
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Project description:A subset of meningiomas progress in histopathological grade and drivers of progression are poorly understood. We aimed to identify somatic mutations and copy number alterations (CNAs) associated with grade progression in a unique matched tumour dataset.
Utilising a prospective database, we identified 10 patients with meningiomas that had undergone grade progression and for whom matched pre- and post-progression tissue (n=50 samples) was available for targeted next-generation sequencing.
Mutations in NF2 were identified in 4/10 patients, 94% were non-skull base tumours. In one patient, three different NF2 mutations were identified in four tumours. NF2 mutated tumours showed large scale CNAs, with highly recurrent losses in 1p, 10, 22q, and frequent CNAs on chromosomes 2, 3 and 4. There was a correlation between grade and CNAs in a subset of patients. In two patients with sphenoid wing Grade III tumours without detected NF2 mutations, a STAT6-NAB2 inversion was identified. Two patients with tumours without detected NF2 mutations showed a combination of loss and high gain on chromosome 17q. Mutations in SETD2, TP53, TERT promoter and NF2 were not uniform across recurrent tumours and did not correspond with grade progression.
Meningiomas that progress in grade generally have a mutational profile already detectable in the pre-progressed tumour, suggesting an aggressive phenotype . CNA profiling shows frequent alterations in NF2 mutated tumours compared to non NF2 mutated tumours and the pattern of CNAs may be associated with grade progression in a subset of cases.
| EGAS00001006585 | EGA
Project description:Meningiomas are frequent central nervous system tumors. Although most meningiomas are benign (WHO grade I) and curable by surgery, WHO grade II and III tumors remain therapeutically challenging due to frequent recurrence. Interestingly, relapse also occurs in some WHO grade I meningiomas. Hence, we investigated the transcriptional features defining aggressive (recurrent, malignantly progressing or WHO grade III) meningiomas in 144 cases. Meningiomas were categorized into non-recurrent (NR), recurrent (R), and tumors undergoing malignant progression (M) in addition to their WHO grade. Unsupervised transcriptomic analysis in 62 meningiomas revealed transcriptional profiles lining up according to WHO grade and clinical subgroup. Notably aggressive subgroups (R+M tumors and WHO grade III) shared a large set of differentially expressed genes (n=332; p<0.01, FC>1.25). In an independent multicenter validation set (n=82), differential expression of 10 genes between WHO grades was confirmed. Additionally, among WHO grade I tumors differential expression between NR and aggressive R+M tumors was af rmed for PTTG1, AURKB, ECT2, UBE2C and PRC1, while MN1 and LEPR discriminated between NR and R+M WHO grade II tumors. Univariate survival analysis revealed a significant association with progression-free survival for PTTG1, LEPR, MN1, ECT2, PRC1, COX10, UBE2C expression, while multivariate analysis identified a prediction for PTTG1 and LEPR mRNA expression independent of gender, WHO grade and extent of resection. Finally, stainings of PTTG1 and LEPR confirmed malignancy-associated protein expression changes. In conclusion, based on the so far largest study sample of WHO grade III and recurrent meningiomas we report a comprehensive transcriptional landscape and two prognostic markers. Comparative transcriptomic analysis of 62 low- and high-grade meningiomas
2016-02-15 | E-GEOD-74385 | biostudies-arrayexpress
Project description:Meningiomas are frequent central nervous system tumors. Although most meningiomas are benign (WHO grade I) and curable by surgery, WHO grade II and III tumors remain therapeutically challenging due to frequent recurrence. Interestingly, relapse also occurs in some WHO grade I meningiomas. Hence, we investigated the transcriptional features defining aggressive (recurrent, malignantly progressing or WHO grade III) meningiomas in 144 cases. Meningiomas were categorized into non-recurrent (NR), recurrent (R), and tumors undergoing malignant progression (M) in addition to their WHO grade. Unsupervised transcriptomic analysis in 62 meningiomas revealed transcriptional profiles lining up according to WHO grade and clinical subgroup. Notably aggressive subgroups (R+M tumors and WHO grade III) shared a large set of differentially expressed genes (n=332; p<0.01, FC>1.25). In an independent multicenter validation set (n=82), differential expression of 10 genes between WHO grades was confirmed. Additionally, among WHO grade I tumors differential expression between NR and aggressive R+M tumors was af rmed for PTTG1, AURKB, ECT2, UBE2C and PRC1, while MN1 and LEPR discriminated between NR and R+M WHO grade II tumors. Univariate survival analysis revealed a significant association with progression-free survival for PTTG1, LEPR, MN1, ECT2, PRC1, COX10, UBE2C expression, while multivariate analysis identified a prediction for PTTG1 and LEPR mRNA expression independent of gender, WHO grade and extent of resection. Finally, stainings of PTTG1 and LEPR confirmed malignancy-associated protein expression changes. In conclusion, based on the so far largest study sample of WHO grade III and recurrent meningiomas we report a comprehensive transcriptional landscape and two prognostic markers.
2016-02-15 | GSE74385 | GEO
Project description:Meningioma is the most common primary brain tumor in adults, but molecular drivers of progression occurring in a subset of meningiomas are poorly understood. We hypothesized that epigenomic variations are causal for the clinical heterogeneity of meningiomas and may be functionally relevant for disease progression. To test this hypothesis, we performed global DNA methylation profiling of a large cross-sectional cohort and a longitudinal cohort of human meningiomas. Our analysis identifies a DNA hypermethylation signature that is correlated with clinical outcomes and enables more accurate prognostication in intermediate-risk meningiomas than previous classification systems. Analyses of longitudinal high-grade meningioma samples in comparison to clinically benign meningiomas and normal meningeal tissue show convergent contributions, but differing plasticity of copy number variations and DNA hypermethylation along the trajectory of meningioma progression. Systematic analysis of DNA hypermethylation in high-grade meningiomas unravel a tumor suppressive role of clustered protocadherins by regulating b-catenin signaling. Together, our study provides fundamental insights into the molecular mechanisms underlying the heterogeneity of clinically benign and aggressive meningiomas and the microevolutionary adaptation during disease progression.
2026-07-01 | GSE304096 | GEO
Project description:Meningioma is the most common primary brain tumor in adults, but molecular drivers of progression occurring in a subset of meningiomas are poorly understood. We hypothesized that epigenomic variations are causal for the clinical heterogeneity of meningiomas and may be functionally relevant for disease progression. To test this hypothesis, we performed global DNA methylation profiling of a large cross-sectional cohort and a longitudinal cohort of human meningiomas. Our analysis identifies a DNA hypermethylation signature that is correlated with clinical outcomes and enables more accurate prognostication in intermediate-risk meningiomas than previous classification systems. Analyses of longitudinal high-grade meningioma samples in comparison to clinically benign meningiomas and normal meningeal tissue show convergent contributions, but differing plasticity of copy number variations and DNA hypermethylation along the trajectory of meningioma progression. Systematic analysis of DNA hypermethylation in high-grade meningiomas unravel a tumor suppressive role of clustered protocadherins by regulating b-catenin signaling. Together, our study provides fundamental insights into the molecular mechanisms underlying the heterogeneity of clinically benign and aggressive meningiomas and the microevolutionary adaptation during disease progression.
2026-07-01 | GSE304094 | GEO
Project description:Meningioma is the most common primary brain tumor in adults, but molecular drivers of progression occurring in a subset of meningiomas are poorly understood. We hypothesized that epigenomic variations are causal for the clinical heterogeneity of meningiomas and may be functionally relevant for disease progression. To test this hypothesis, we performed global DNA methylation profiling of a large cross-sectional cohort and a longitudinal cohort of human meningiomas. Our analysis identifies a DNA hypermethylation signature that is correlated with clinical outcomes and enables more accurate prognostication in intermediate-risk meningiomas than previous classification systems. Analyses of longitudinal high-grade meningioma samples in comparison to clinically benign meningiomas and normal meningeal tissue show convergent contributions, but differing plasticity of copy number variations and DNA hypermethylation along the trajectory of meningioma progression. Systematic analysis of DNA hypermethylation in high-grade meningiomas unravel a tumor suppressive role of clustered protocadherins by regulating b-catenin signaling. Together, our study provides fundamental insights into the molecular mechanisms underlying the heterogeneity of clinically benign and aggressive meningiomas and the microevolutionary adaptation during disease progression.
2026-07-01 | GSE304093 | GEO
Project description:Meningioma is the most common primary brain tumor in adults, but molecular drivers of progression occurring in a subset of meningiomas are poorly understood. We hypothesized that epigenomic variations are causal for the clinical heterogeneity of meningiomas and may be functionally relevant for disease progression. To test this hypothesis, we performed global DNA methylation profiling of a large cross-sectional cohort and a longitudinal cohort of human meningiomas. Our analysis identifies a DNA hypermethylation signature that is correlated with clinical outcomes and enables more accurate prognostication in intermediate-risk meningiomas than previous classification systems. Analyses of longitudinal high-grade meningioma samples in comparison to clinically benign meningiomas and normal meningeal tissue show convergent contributions, but differing plasticity of copy number variations and DNA hypermethylation along the trajectory of meningioma progression. Systematic analysis of DNA hypermethylation in high-grade meningiomas unravel a tumor suppressive role of clustered protocadherins by regulating b-catenin signaling. Together, our study provides fundamental insights into the molecular mechanisms underlying the heterogeneity of clinically benign and aggressive meningiomas and the microevolutionary adaptation during disease progression.
2026-07-01 | GSE304087 | GEO
Project description:Meningiomas in pediatric and adolescent/young adult patients are poorly characterized biologically and clinically, and risk stratification is largely extrapolated from adult tumors. We analyzed 293 tumors from patients aged 0–39 years using integrated histopathological and molecular profiling. Youth-onset meningiomas were enriched for NF2 and SMARCE1 alterations and exhibited a gain-dominated copy-number landscape, including recurrent chr17q gain, whereas canonical adult high-risk features, such as chr1p loss, lacked prognostic significance. Adult-derived prognostic frameworks—including WHO grade, methylation-based stratification, and integrated risk scores—failed to predict progression in patients ≤21 years. Tumors segregated into age-enriched epigenetic clusters defined by SMARCE1, NF2, and BAP1 alterations. Among NF2-altered tumors, patterns of Merlin inactivation shaped by germline status and co-occurring copy-number variations delineated biologically divergent subsets. Across all groups, extent of resection remained the strongest predictor of outcome. These findings define pediatric and young adult meningiomas as a distinct molecular entity requiring age-adapted risk stratification.
2026-06-08 | GSE317578 | GEO
Project description:Meningiomas are common brain tumors that are classified into three World Health Organization grades (Grade I: benign, Grade II: atypical and Grade III: malignant) and are molecularly ill-defined tumors. The purpose of this study was identify microRNA (miRNA) molecular signatures unique to the different grades of meningiomas correlating them to prognosis. We have used a miRNA expression microarray to show that meningiomas of all three grades fall into two main molecular groups designated “benign” and “malignant” meningiomas. While all typical meningiomas fall into the benign group and all anaplastic meningiomas fall into the malignant group, atypical meningiomas distribute into either one of these groups. We have identified a miRNA signature that distinguishes benign meningiomas from malignant meningiomas. We studied the gene expression profiles of 340 mammalian miRNAs in 37 primary meningioma tumors by means of DNA microarrays.
2011-01-02 | E-GEOD-19720 | biostudies-arrayexpress
Project description:Although meningiomas are one of the most frequent primary intracranial tumors, there are only a few studies dealing with gene regulation processes in meningiomas. MiRNAs are key regulators of gene expression and regulation and miRNA profiles offer themselves as biomarkers for cancer development and progression. To investigate the role of miRNAs during meningioma growth and progression, we compared expression of 1205 miRNAs in 55 meningioma samples of different tumor grades and histological subtypes. We were able to classify histological subtypes in WHO grade I meningiomas with up to 97% accuracy (meningothelial versus fibroblastic) and different WHO grades with up to 93% accuracy (WHO I versus WHO III). We found significant downregulation of miRNAs on chromosome 1p36 and within two large miRNA clusters on 14q32 in high grade meningiomas, two regions that are yet associated with meningioma progression. We also identified several miRNAs associated with epithelial to mesenchymal transition differentially expressed in meningothelial meningioma compared to fibroblastic meningioma. Combined, our data show that meningiomas of different WHO grades and histological subtypes show a specific miRNA expression profile. Some individual miRNAs can also serve as potential biomarkers for meningioma progression.
2014-12-31 | GSE50641 | GEO