Glioma sequencing data
Ontology highlight
ABSTRACT:
PROVIDER: EGAS00001006355 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:The discovery of the oncometabolite 2-hydroxyglutarate in isocitrate dehydrogenase 1-mutated (IDH1-mutated) tumor entities affirmed the role of metabolism in cancer. However, large databases with tissue metabolites that are modulated by IDH1 mutation remain an area of development. Here, we present an unprecedented and valuable resource for tissue metabolites in diffuse glioma and their modulations by IDH1 mutation, histology, and tumor treatments in 101 tissue samples from 73 diffuse glioma patients (24 astrocytoma, 17 oligodendroglioma, 32 glioblastoma), investigated by NMR-based metabolomics and supported by RNA-Seq. We discovered comparison-specific metabolites and pathways modulated by IDH1 (IDH1 mutation status cohort) and tumor entity. The Longitudinal investigation cohort provides metabolic profiles of untreated and corresponding treated glioma samples at first progression. Most interestingly, univariate and multivariate cox regressions and Kaplan-Meier analyses revealed that tissue metabolites correlate with progression-free and overall survival. Thus, this study introduces potentially novel candidate prognostic and surrogate metabolite biomarkers for future prospective clinical studies, aiming at further refining patient stratification in diffuse glioma. Furthermore, our data will facilitate the generation of so-far-unanticipated hypotheses for experimental studies to advance our molecular understanding of glioma biology.
2022-09-07 | MTBLS3873 | MetaboLights
Project description:We used MHC-I immunopeptidomics to study how MTX-241F, a selective EGFR/PI3K inhibitor, alters antigen presentation in diffuse midline glioma (H3K27M) and glioblastoma xenografts. MHC-I–bound peptides from vehicle- and drug-treated tumors were profiled by LC–MS/MS to identify tumor- and treatment-specific peptides, including candidate brain-enriched biomarkers and immunotherapy targets.
2026-02-10 | PXD070941 | Pride
Project description:Mutations in the gene encoding histone H3, p.K28M(K27M) and p.G35R/V(G34R/V), are the major driver gene mutations in gliomas. H3 p.K28M(K27M) mutations are frequently found in gliomas arising in midline structures, so called H3K27M-diffuse midline glioma (DMG), while H3 p.G35R/V(G34R/V) mutations are frequently found in pediatric hemispheric gliomas, so called H3G34R/V-diffuse hemispheric glioma (DHG). In contrast, hemispheric glioma with H3 p.K28M(K27M) mutation, known as H3K27M-DHG, is a rare entity and its clinical and molecular characteristics remain to be fully elucidated. We describe a 41-year-old female patient with the right parietal lobe tumor. Following a gross total resection, the pathology showed a high-grade astrocytoma. Sanger sequencing revealed an H3K27M mutation and an IDH1/2-wildtype, leading to the integrated diagnosis of H3K27M-DHG. She underwent chemoradiotherapy with temozolomide and suffered recurrences twice until her death 55 months after the initial diagnosis. The deoxyribonucleic acid methylation profiling classified the tumor as DMG, H3K27-altered, suggesting that it molecularly belonged to the variant of DMG despite a non-median location. Next-generation sequencing on the recurrent tumor detected fibroblast growth factor receptor (FGFR)1 mutation, a favorable prognostic factor in H3K27M-DMG. A relatively prolonged survival of our patient suggests that FGFR1 mutations may also contribute to a better prognosis in H3K27M-DHG.
2025-12-31 | GSE286743 | GEO
Project description:Anaplastic ependymoma and H3K27M-mutant diffuse midline glioma were analyzed and compared by scRNA-seq.
2024-02-28 | GSE245674 | GEO
Project description:PDGFRA and H3.3 mutations cooperate in an iPSC-based model of diffuse midline glioma to alter tumor biology.
2026-03-01 | GSE225491 | GEO
Project description:PDGFRA and H3.3 mutations cooperate in an iPSC-based model of diffuse midline glioma to alter tumor biology.
2023-06-14 | GSE225490 | GEO
Project description:Adult diffuse gliomas are the deadliest brain tumours including IDH-wildtype glioblastomas of worst prognosis and diffuse low grade IDH-mutant astrocytomas and oligodendrogliomas. These glial tumours display distinct tumoral cell population defeating current therapies. Our group has previously unveiled the role of NOTCH signalling in glioblastoma cell plasticity and in the conversion of oligodendrocytic-like to astrocytic-like tumoral cells in IDH-mutant low-grade gliomas which escalate inevitably to higher grade malignant gliomas. To gain insight into signalling pathways regulating glioma cell plasticity and malignancy, we focused our work on endothelin signalling including endothelin peptide ligands (ET-1, ET-2, ET-3) binding to G-protein coupled endothelin receptors A and B (EDNRA, EDNRB). Here, using glioma patient samples and glioma patient-derived cell lines, we showed that endothelin reduces glioma cell proliferation while increasing migration initiating a proneural to mesenchymal transition. Mechanistically, EDNRB activation led to IP3-dependent calcium mobilization, apamin-sensitive KCNN2/KCNN3 potassium currents and phosphorylation of ERK1/2 and STAT3 in glioma cells. Finally, we studied endothelin receptor regulation by tumoral microenvironment stimuli highlighting a role for EDNRA induced by NOTCH1 and hypoxia in perivascular hypoxic area in glioblastoma. Altogether, this study demonstrates endothelin signalling as a key player in mesenchymal transformation of diffuse IDH-mutant gliomas and glioblastomas.
2026-03-11 | PXD065902 | Pride
Project description:Neural-tumor interactions drive glioma growth as evidenced in preclinical models, but clinical validation is limited. We present an epigenetically defined neural signature of glioblastoma that independently predicts patients’ survival. We use reference signatures of neural cells to deconvolve tumor DNA and classify samples into low- or high-neural tumors. High-neural glioblastomas exhibit hypomethylated CpG sites and upregulation of genes associated with synaptic integration. Single-cell transcriptomic analysis reveals a high abundance of stem cell-like malignant cells in high-neural glioblastoma, primarily of the neural lineage. These cells are further classified as neural precursor cell-like, astrocyte cell-like, and oligodendrocyte precursor-like, alongside oligodendrocytes and neurons. In line with these findings, high-neural glioblastoma cells engender neuron-to-glioma synapse formation in vitro and in vivo and show an unfavorable survival after xenografting. In patients, a high-neural signature associated with decreased survival. High-neural tumors also exhibit increased functional connectivity in magnetencephalography and resting-state magnet resonance imaging and can be detected via DNA analytes and brain-derived neurotrophic factor in patients’ plasma. The prognostic importance of the neural signature was further validated in patients diagnosed with diffuse midline glioma. Our study presents an epigenetically defined malignant neural signature in high-grade gliomas that is prognostically relevant. High-neural gliomas likely require a maximized surgical resection approach for improved outcomes.
2024-03-20 | GSE240704 | GEO
Project description:Background: Signaling by receptor tyrosine kinases (RTK) is frequently dysregulated in gliomas. Inter-individual variability in the causes for dysregulated RTK signaling may have hampered the efficacy of targeted therapies. Using gene expression modules around key regulators in the RAS-RAF-MEK-MAPK cascade and in the phosphatidylinositol 3-kinase-AKT pathways, we developed a âRMPAâ clustering scheme to distinguish gliomas with varying extents of RTK signaling. Results: We identified gene modules consistently co-expressed with NF1 (NF1-M), Sprouty (SPRY-M) and PTEN (PTEN-M) in gliomas. Their signatures enabled robust clustering of adult diffuse gliomas of WHO grades II-IV into RMPAhigh and RMPAlow phenotypes in a morphology-independent manner. In five independent data sets from three continents containing more than 1500 adult diffuse gliomas, RMPAhigh gliomas were associated with poor prognosis while RMPAlow gliomas were not. The RMPAhigh and RMPAlow glioma subtypes showed distinct levels of the activities of RAS-RAF-MEK-MAPK cascade and PI3K-AKT pathway and harbored unique sets of genomic alterations in the RTK signaling-related genes. The RMPAhigh gliomas contained large numbers of immature vessel cells and tumor associated macrophages and both cell types expressed high levels of pro-angiogenic RTKs including MET, VEGFR1, KDR, EPHB4 and NRP1. Conclusion: Inter-glioma variability in RTK signaling activities can be defined using the RMPA clustering scheme. The combined signatures of NF1-M, SPRY-M and PTEN-M reflect RTK signaling activity both in the glioma cells and in the glioma microenvironment. Our data show that RTK signaling in the glioma microenvironment may play a pivotal role in glioma progression. Transcriptome data from 22 fresh gliomas (2 astrocytoma II, 1 oligodendrocytoma II, 7 oligoastrocytoma II, 4 anaplastic oligoastrocytoma III and 8 GBM) were obtained using Affymetrix Human Gene 1.0 ST Array. Unsupervised hierarchical clustering of the expression data for the SPRY-M, NF1-M and PTEN-M was performed on these transcriptome data to identify samples with RMPAhigh or RMPAlow signature.
2015-10-30 | E-GEOD-74462 | biostudies-arrayexpress
Project description:High-grade gliomas (HGG) are deadly diseases for both adult and pediatric patients. Recently, it has been shown that neuronal activity promotes the progression of multiple subgroups of HGG. However, epigenetic mechanisms that govern this process remain elusive. Here we report that the chromatin remodeler CHD2 regulates neuron-glioma interactions in diffuse midline glioma (DMG) characterized by onco-histone H3.1K27M. Depletion of CHD2 in H3.1K27M DMG cells compromises cell viability and neuron-to-glioma synaptic connections in vitro, neuron-induced proliferation of H3.1K27M HGG DMG cells in vitro and in vivo, activity-dependent calcium transients in vivo, and extends the survival of H3.1K27M DMG-bearing mice. Mechanistically, CHD2 coordinates with the transcription factor FOSL1 to control the expression of axon-guidance and synaptic genes in H3.1K27M DMG cells. Together, our study reveals a mechanism whereby CHD2 controls the intrinsic gene program of the H3.1K27M DMG subtype, which in turn regulates the tumor growth-promoting interactions of glioma cells with neurons.
2024-05-09 | GSE211074 | GEO