Characterization of a diffuse low and high grade glioma cell line biobank
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE308063 | GEO | 2026/01/13
REPOSITORIES: GEO
Similar Datasets
Project description:We perform high-throughput single-nucleus RNA and ATAC sequencing (snRNA- and snATAC-seq) on primary IDH mutant gliomas and snRNA-seq on a cohort of primary and recurrent IDH mutant glioma pairs to comprehensively resolve tumor diversity and TAM states. Our results resemble previously described differentiation hierarchies, but also reveal a novel group of epigenetically and transcriptionally distinct non-cycling stem-like tumor cells in diffuse gliomas. Further, we identify significant transcriptional differences in TAM states between oligodendrogliomas and astrocytomas, with a notable interaction between immunosuppressive TAMs and astrocytic tumor subpopulations in astrocytomas. These results suggest that TAM-tumor interactions may contribute to the clinical course of oligodendrogliomas and astrocytomas.
2023-09-20 | GSE205771 | GEO
Project description:Mutations in isocitrate dehydrogenase 1 or 2 (IDH1/2) define glioma subtypes and are 38 considered primary events in gliomagenesis, impacting tumor epigenetics and metabolism. 39 IDH enzymes are crucial for the generation of reducing potential, yet the impact of the mutation 40 on the cellular antioxidant system is not understood. Here, we investigate how glutathione 41 (GSH) levels are maintained in IDH1 mutant gliomas, despite an altered NADPH/NADP 42 balance. We find that IDH1 mutant astrocytomas specifically upregulate cystathionine γ-lyase 43 (CSE), the enzyme responsible for cysteine production upstream of GSH biosynthesis. Genetic 44 and chemical interference with CSE in patient-derived glioma cells carrying the endogenous 45 IDH1 mutation, sensitized tumor cells to cysteine depletion, an effect not observed in IDH1 46 wild-type gliomas. This correlated with reduced GSH synthesis as shown by in vitro and in vivo 47 serine tracing and led to delayed tumor growth in mice. Thus we show that IDH1 mutant 48 astrocytic gliomas critically rely on NADPH-independent de novo GSH synthesis to maintain 49 the antioxidant defense, which uncovers a novel metabolic vulnerability in this dismal disease.
2021-11-25 | PXD022752 | Pride
Project description:Adult-type diffuse gliomas comprise IDH-mutant astrocytomas, IDH-mutant 1p/19q codeleted oligodendrogliomas (ODG), and IDH-wildtype glioblastomas (GBM). GBM display genome instability, which may result from two genetic events leading to massive chromosome alterations: chromothripsis (CT) and whole-genome duplication (WGD). The better prognosis of the latter may be related to their genome stability compared to GBM. Pangenomic profiles of 297 adult diffuse gliomas were analyzed at initial diagnosis using SNP arrays, including 192 GBM and 105 IDH-mutant gliomas (61 astrocytomas and 44 ODG). Tumor ploidy was assessed with Genome Alteration Print and CT events with CTLPScanner and through manual screening.
2024-12-24 | E-MTAB-13542 | biostudies-arrayexpress
Project description:Gene expression profiling of 23 grade II gliomas of different histological subtype. Analyses was done on 9 astrocytomas, 8 oligoastrocytomas and 6 oligodendrogliomas.
2007-05-01 | E-MEXP-938 | biostudies-arrayexpress
Project description:Human astrocytomas and oligodendrogliomas are defined by mutations in the metabolic enzyme isocitrate dehydrogenase (IDH) 1 or 2. Mutant IDH1 causes the production and accumulation of the metabolite 2 hydroxyglutarate, which induces genome-wide hypermethylation, and is thought to be a driver mutation of these tumours. However, there are multiple contradictory effects of mutant IDH1 in cell lines and in vivo models, prompting us to study the effect of mutant IDH1 on cell differentiation, proliferation, and apoptosis. Here we established mouse glioma initiating cells (GIC) by inactivating the tumour suppressor genes Pten and p53 in the neural stem/progenitor cell population of the forebrain, and compared these GIC with triple mutant tumours expressing in addition the Idh1 R132H mutation. We found that Idh1 mutant cells proliferate less in vitro and mice with Idh1 mutant tumour survived significantly longer than their Idh1 wild type counterparts. By comparing the RNA expression profiles of Idh wild-type and Idh mutant cells and tumours we identified endoplasmic reticulum stress pathways were significantly associated with Idh1 mutation.
2019-08-22 | GSE119741 | GEO
Project description:Oligodendrogliomas are defined by IDH-mutations and codeletions of chromosomal arms 1p and 19q. In the past, case reports and small studies described gliomas with sarcomatous features arising from oligodendrogliomas, so called oligosarcomas. Here, we report a series of 23 IDH-mutant oligosarcomas forming a distinct methylation class. The tumors were recurrences from prior oligodendrogliomas or developed de novo. Precursor tumors of 11 oligosarcomas were histologically and molecularly indistinguishable from conventional oligodendrogliomas. Oligosarcoma tumor cells were embedded in a dens network of reticulin fibers, frequently showing p53 accumulation, positivity for SMA, and gain of H3K27 trimethylation (H3K27me3) as compared to primary lesions. In 5 oligosarcomas no 1p/19q codeletion was detectable, although it was present in the primary lesions. Oligosarcomas harbored an increased chromosomal copy number variation load with frequent CDKN2A/B deletions. Proteomic profiling demonstrated oligosarcomas to be highly distinct from conventional grade 3 oligodendrogliomas with consistent evidence for a smooth muscle differentiation. Expression of several tumor suppressors was reduced with NF1 being lost frequently. In contrast, oncogenic YAP1 was aberrantly overexpressed in oligosarcomas. Panel sequencing revealed mutations in NF1 and TP53 along with IDH1/2 and TERT promoter mutations. Survival of patients was significantly poorer for oligosarcomas than for grade 3 oligodendrogliomas and comparable to that of grade 4 IDH-mutant astrocytomas. These results establish oligosarcoma as a distinct type of IDH-mutant glioma differing from conventional oligodendrogliomas on the histologic, epigenetic, proteomic, molecular and clinical level. Diagnosis can be based on the characteristic DNA methylation profile or the combined evidence of sarcomatous histology, IDH-mutation and an oligodendroglioma-typical molecular alteration as TERT promoter mutation and/or 1p/19q codeletion.
2022-01-01 | GSE190362 | GEO
Project description:Oligodendrogliomas are defined by IDH-mutations and codeletions of chromosomal arms 1p and 19q. In the past, case reports and small studies described gliomas with sarcomatous features arising from oligodendrogliomas, so called oligosarcomas. Here, we report a series of 23 IDH-mutant oligosarcomas forming a distinct methylation class. The tumors were recurrences from prior oligodendrogliomas or developed de novo. Precursor tumors of 11 oligosarcomas were histologically and molecularly indistinguishable from conventional oligodendrogliomas. Oligosarcoma tumor cells were embedded in a dens network of reticulin fibers, frequently showing p53 accumulation, positivity for SMA, and gain of H3K27 trimethylation (H3K27me3) as compared to primary lesions. In 5 oligosarcomas no 1p/19q codeletion was detectable, although it was present in the primary lesions. Oligosarcomas harbored an increased chromosomal copy number variation load with frequent CDKN2A/B deletions. Proteomic profiling demonstrated oligosarcomas to be highly distinct from conventional grade 3 oligodendrogliomas with consistent evidence for a smooth muscle differentiation. Expression of several tumor suppressors was reduced with NF1 being lost frequently. In contrast, oncogenic YAP1 was aberrantly overexpressed in oligosarcomas. Panel sequencing revealed mutations in NF1 and TP53 along with IDH1/2 and TERT promoter mutations. Survival of patients was significantly poorer for oligosarcomas than for grade 3 oligodendrogliomas and comparable to that of grade 4 IDH-mutant astrocytomas. These results establish oligosarcoma as a distinct type of IDH-mutant glioma differing from conventional oligodendrogliomas on the histologic, epigenetic, proteomic, molecular and clinical level. Diagnosis can be based on the characteristic DNA methylation profile or the combined evidence of sarcomatous histology, IDH-mutation and an oligodendroglioma-typical molecular alteration as TERT promoter mutation and/or 1p/19q codeletion.
2022-01-01 | GSE190364 | GEO
Project description:Human astrocytomas and oligodendrogliomas are defined by mutations in the metabolic enzyme isocitrate dehydrogenase (IDH) 1 or 2. Mutant IDH1 causes the production and accumulation of the metabolite 2 hydroxyglutarate, which induces genome-wide hypermethylation, and is thought to be a driver mutation of these tumours. However, there are multiple contradictory effects of mutant IDH1 in cell lines and in vivo models, prompting us to study the effect of mutant IDH1 on cell differentiation, proliferation, and apoptosis. Here we established mouse glioma initiating cells (GIC) by inactivating the tumour suppressor genes Pten and p53 in the neural stem/progenitor cell population of the forebrain, and compared these GIC with triple mutant tumours expressing in addition the Idh1 R132H mutation. We found that Idh1 mutant cells proliferate less in vitro and mice with Idh1 mutant tumour survived significantly longer than their Idh1 wild type counterparts. By comparing the miRNA expression profiles of Idh wild-type and Idh mutant cells and tumours we identified miR-183-5p as a differentially expressed miRNA.
2019-08-22 | GSE119740 | GEO
Project description:Oligodendrogliomas are defined by IDH-mutations and codeletions of chromosomal arms 1p and 19q. In the past, case reports and small studies described gliomas with sarcomatous features arising from oligodendrogliomas, so called oligosarcomas. Here, we report a series of 23 IDH-mutant oligosarcomas forming a distinct methylation class. The tumors were recurrences from prior oligodendrogliomas or developed de novo. Precursor tumors of 11 oligosarcomas were histologically and molecularly indistinguishable from conventional oligodendrogliomas. Oligosarcoma tumor cells were embedded in a dens network of reticulin fibers, frequently showing p53 accumulation, positivity for SMA, and gain of H3K27 trimethylation (H3K27me3) as compared to primary lesions. In 5 oligosarcomas no 1p/19q codeletion was detectable, although it was present in the primary lesions. Oligosarcomas harbored an increased chromosomal copy number variation load with frequent CDKN2A/B deletions. Proteomic profiling demonstrated oligosarcomas to be highly distinct from conventional grade 3 oligodendrogliomas with consistent evidence for a smooth muscle differentiation. Expression of several tumor suppressors was reduced with NF1 being lost frequently. In contrast, oncogenic YAP1 was aberrantly overexpressed in oligosarcomas. Panel sequencing revealed mutations in NF1 and TP53 along with IDH1/2 and TERT promoter mutations. Survival of patients was significantly poorer for oligosarcomas than for grade 3 oligodendrogliomas and comparable to that of grade 4 IDH-mutant astrocytomas. These results establish oligosarcoma as a distinct type of IDH-mutant glioma differing from conventional oligodendrogliomas on the histologic, epigenetic, proteomic, molecular and clinical level. Diagnosis can be based on the characteristic DNA methylation profile or the combined evidence of sarcomatous histology, IDH-mutation and an oligodendroglioma-typical molecular alteration as TERT promoter mutation and/or 1p/19q codeletion.
2021-12-16 | MSV000088571 | MassIVE
Project description:Low grade gliomas (LGG; WHO grade 2 astrocytomas, oligodendrogliomas and oligoastrocytomas) account for about 25% of diffuse gliomas. Most occur in young adults between the ages of 30 and 45 years, and are usually only diagnosed after a seizure. In general, they can be characterised by a long period of continuous slow growth, followed by malignant transformation that will be the cause of death up to 25 years after onset. However, there is a significant number of patients for whom malignant progression is more rapid, with mortality observed within 5 years. This suggests that, as with other tumour types, there may be different subtypes of LGG with specific prognosis. It follows that being able to identify these subtypes may permit better patient stratification and aid targeted treatments. Until recently, our understanding of the variables involved in patient prognosis included the type of tumour oligodendroglial tumours indicate better prognosis than oligoastrocytic or astrocytic and presence of the 1p-19q co-deletion. In addition, the recent discovery of mutations in IDH1&2 in the majority of LGGs provided another means of stratifying patients, while offering an important insight into their biology. However, we still understand very little of the biology behind the genesis and progression of the 70-80% of LGG that bear IDH1&2 mutations, let alone the remaining IDH wild-type tumours.
2015-07-07 | E-MTAB-3708 | biostudies-arrayexpress