Project description:We report RNA sequencing of 185 meningiomas, which are used to interrogate the biology underlying DNA methylation groups of meningioma.
Project description:We report single-cell RNA sequencing of 23 PDX meningiomas that underwent radiation therapy, were treated with a Notch3 neutralizing antibody, or overexpressed Notch3.
Project description:Aims: Whereas recent molecular analysis has revealed that sporadic meningioma has various genetic, epigenetic, and transcriptomic profiles, those of meningioma in NF2 patients are not fully elucidated. This study probed meningiomas' clinical, histological, and molecular characteristics in NF2 patients. Methods: A long-term retrospective follow-up (13.5 ± 5.5 years) study involving 159 meningiomas in NF2 patients was performed. We assessed their characteristics by performing immunohistochemistry (IHC), bulk-RNA sequencing, and copy number analysis. All variables of meningiomas in NF2 patients were compared with those of 189 sporadic NF2-altered meningiomas. Results: Most meningiomas in NF2 patients were stable, and the mean annual growth rate was 1.0 ± 1.8 cm3/yr. Twenty-eight meningiomas (17.6%) in 25 patients (43.1%) were resected during the follow-up period. WHO grade 1 meningiomas in NF2 patients` were more frequent than in sporadic NF2-altered meningiomas (92.9% vs 80.9%). Transcriptomic analysis for NF2 patients`/sporadic NF2-altered WHO grade 1 meningiomas (n = 14 versus 15, respectively) showed that tumours in NF2 patients had still higher immune response and immune cell infiltration than sporadic NF2-altered meningiomas. Furthermore, RNA-seq/IHC-derived immunophenotyping corroborated this higher immune response by identifying myeloid cell infiltration, especially macrophages. Conclusions: Clinical, histological, and transcriptomic analyses for meningiomas in NF2 patients demonstrated that meningiomas in NF2 patients showed less aggressive behaviour than sporadic NF2-altered meningiomas and elicited marked immune response by identifying myeloid cell infiltration, especially macrophages.
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
Project description:Correlate the gene expression profiles with the most relevant patterns of chromosome abnormalities (cytogenetic subgroups of meningiomas) and the gene expression profiles could help to explain the differences in clinical behaviour of meningiomas. The impact of tumor cytogenetics on the gene expression analyzed in meningiomas. Here, we analyzed the gene expression profiles (GEP) of 47 tumors and correlated them with the most clinical relevant cytogenetic subgroups of meningiomas, including diploid tumors, isolated -22/22q-, del(1p36) alone and complex karyotypes associated with del(1p36) and/or -14q. In addition, 4 samples containing purified RNA extracted from normal meningeal cells (BioChain Institute, Hayward, CA and US Biological, Swampscott, MA, USA) were also processed.
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.
Project description:Meningiomas, one of the most common human brain tumors, are derived from arachnoidal cells associated with brain meninges, usually benign and frequently associated with neurofibromatosis type 2. Here we define a human meningioma-typical miRNA profile and characterize effects of one down-regulated miRNA, miR-200a, on tumor growth. Elevated levels of miR-200a inhibited meningioma cell growth in culture and in a tumor model in vivo. Up-regulation of miR-200a decreased expression of transcription factors, ZEB1 and SIP1, with consequently increased expression of E-cadherin, an adhesion protein associated with cell differentiation. Down-regulation of miR-200a in meningiomas and arachnoidal cells resulted in increased expression of β -catenin and cyclin D1 involved in cell proliferation. miR-200a was found to directly target β -catenin mRNA, thereby inhibiting its translation and blocking β -catenin-Wnt signaling, frequently involved in cancer. A direct correlation was found between down-regulation of miR-200a and up-regulation of β-catenin in human meningioma samples. Thus, miR-200a appears to act as a multi-functional tumor suppressor miRNA in meningiomas through effects on the E-cadherin and β -catenin-Wnt signaling pathways. This reveals a previously unrecognized signaling cascade involved in meningioma tumor development and highlights a novel molecular interaction between miR-200a and Wnt signaling, thereby providing insights into novel therapies for meningiomas.
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.