Homo sapiens
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: E-GEOD-52942
PROVIDER: PRJNA230506 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Comparison of gene expression profiles of anaplastic glioma with or without the mutated IDH1/2 gene
2015-08-25 | E-GEOD-52942 | ExpressionAtlas
Project description:To examine the NRF2 activity in anaplastic glioma with mutated IDH1/2, we conducted the microarray analysis to measure the expression levels of representative NRF2 target genes, including NQO1, HMOX1, GCLM, TXNRD1, and PRDX1. 12 anaplastic gliomas with or without mutated IDH1/2.
2013-12-04 | E-GEOD-52942 | biostudies-arrayexpress
Project description:To examine the NRF2 activity in anaplastic glioma with mutated IDH1/2, we conducted the microarray analysis to measure the expression levels of representative NRF2 target genes, including NQO1, HMOX1, GCLM, TXNRD1, and PRDX1.
2013-12-04 | GSE52942 | GEO
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:The R132H mutation in the metabolic enzyme isocitrate dehydrogenase 1 (IDH1) is the most important prognostic factor for survival of glioma patients. This resulted in many studies investigating the effects of this mutation, including those on energy metabolism. This led to the discovery of a panel of enzymes mainly involved in glutamate anaplerosis and aerobic glycolysis that change in abundance as a result of the IDH1 mutation. To further study these changes and investigate the therapeutic value of inhibitors of IDH1 R132H-associated metabolic pathways, appropriate glioma models are required that mimic in vivo metabolism as good as possible. To investigate how metabolism is affected by in vitro cell culture, we here compared surgically obtained snap frozen glioma tissues with their corresponding primary glioma cell culture models with a previously developed targeted mass spectrometry proteomic assay. We determined the relative abundance of a panel of metabolic enzymes. Results confirmed increased glutamate use and decreased aerobic glycolysis in resected IDH1 R132H glioma tissue samples. However, these metabolic profiles were not reflected in the paired glioma culture samples. Analysis of orthotopic glioma xenograft samples with and without the IDH1 mutation revealed metabolic profiles that more closely resembled clinical counterparts. We suggest that culture conditions and tumor microenvironment play a crucial role in maintaining the in vivo metabolic situation in cell culture models. For this reason, new models that more closely resemble the in vivo microenvironment, such as 3-dimensional cell co-cultures or organotypic multicellular spheroid models, need to be developed and investigated.
2022-02-16 | PXD024019 | Pride
Project description:The R132H mutation in the metabolic enzyme isocitrate dehydrogenase 1 (IDH1) is the most important prognostic factor for survival of glioma patients. This resulted in many studies investigating the effects of this mutation, including those on energy metabolism. This led to the discovery of a panel of enzymes mainly involved in glutamate anaplerosis and aerobic glycolysis that change in abundance as a result of the IDH1 mutation. To further study these changes and investigate the therapeutic value of inhibitors of IDH1 R132H-associated metabolic pathways, appropriate glioma models are required that mimic in vivo metabolism as good as possible. To investigate how metabolism is affected by in vitro cell culture, we here compared surgically obtained snap frozen glioma tissues with their corresponding primary glioma cell culture models with a previously developed targeted mass spectrometry proteomic assay. We determined the relative abundance of a panel of metabolic enzymes. Results confirmed increased glutamate use and decreased aerobic glycolysis in resected IDH1 R132H glioma tissue samples. However, these metabolic profiles were not reflected in the paired glioma culture samples. Analysis of orthotopic glioma xenograft samples with and without the IDH1 mutation revealed metabolic profiles that more closely resembled clinical counterparts. We suggest that culture conditions and tumor microenvironment play a crucial role in maintaining the in vivo metabolic situation in cell culture models. For this reason, new models that more closely resemble the in vivo microenvironment, such as 3-dimensional cell co-cultures or organotypic multicellular spheroid models, need to be developed and investigated.
2022-02-14 | PXD024009 | Pride
Project description:The discovery of the IDH1 R132H (IDH1 mut) mutation in low-grade glioma and the associated change in function of the IDH1 enzyme has increased the interest in glioma metabolism. In an earlier study, we found that changes in expression of genes involved in the aerobic glycolysis and the TCA-cycle are associated with IDH1 mut. Here we apply proteomics to FFPE samples of diffuse gliomas with or without IDH1 mutations, in order to map changes in protein levels associated with this mutation. We observed significant changes in the enzyme abundance associated with aerobic glycolysis, glutamate metabolism and the TCA-cycle in IDH1 mut gliomas. Specifically, the enzymes involved in the metabolism of glutamate, lactate and enzymes involved in the conversion of α-ketoglutarate were increased in IDH1 mut gliomas. In addition, the bicarbonate transporter (SLC4A4) was increased in IDH1 mut gliomas, supporting the idea that a mechanism preventing intracellular acidification is active. We also found that enzymes that convert proline, valine, leucine and isoleucine into glutamate were increased in IDH1 mut glioma. We conclude that in IDH1 mut glioma metabolism is rewired (increased input of lactate and glutamate) to preserve TCA cycle activity in IDH1 mut gliomas.
2020-03-09 | PXD016698 | Pride
Project description:The discovery of the IDH1 R132H (IDH1 mut) mutation in low-grade glioma and the associated change in function of the IDH1 enzyme has increased the interest in glioma metabolism. In an earlier study, we found that changes in expression of genes involved in the aerobic glycolysis and the TCA-cycle are associated with IDH1 mut. Here we apply proteomics to FFPE samples of diffuse gliomas with or without IDH1 mutations, in order to map changes in protein levels associated with this mutation. We observed significant changes in the enzyme abundance associated with aerobic glycolysis, glutamate metabolism and the TCA-cycle in IDH1 mut gliomas. Specifically, the enzymes involved in the metabolism of glutamate, lactate and enzymes involved in the conversion of α-ketoglutarate were increased in IDH1 mut gliomas. In addition, the bicarbonate transporter (SLC4A4) was increased in IDH1 mut gliomas, supporting the idea that a mechanism preventing intracellular acidification is active. We also found that enzymes that convert proline, valine, leucine and isoleucine into glutamate were increased in IDH1 mut glioma. We conclude that in IDH1 mut glioma metabolism is rewired (increased input of lactate and glutamate) to preserve TCA cycle activity in IDH1 mut gliomas.
2020-03-09 | PXD016697 | Pride
Project description:Pilot study aimed at comparing miRNA profiles of human glioma cells with and without the R132H IDH1 mutation.
2016-04-30 | GSE80821 | GEO
Project description:The recent discovery of mutations in metabolic enzymes has rekindled interest in harnessing the altered metabolism of cancer cells for cancer therapy. One potential drug target is isocitrate dehydrogenase 1 (IDH1) which is mutated in multiple human cancers. Here, we examine the role of mutant IDH1 in fully transformed cells with endogenous IDH1 mutations. A selective R132H-IDH1 inhibitor (AGI-5198) identified through a high-throughput screen dose-dependently blocked the ability of the mutant enzyme (mIDH1) to produce R-2-hydroxyglutarate (R-2HG). Under conditions of near complete R-2HG inhibition, the mIDH1 inhibitor induced demethylation of histone H3K9M3 and expression of genes associated with gliogenic differentiation. Blockade of mIDH1 impaired the growth of IDH1-mutant - but not IDH1-wildtype – glioma cells without appreciable changes in genome wide DNA methylation. These data suggest that mIDH1 may promote glioma growth through mechanisms beyond its well-characterized epigenetic effects. Xenograft experiments were carried out with treatment cohorts of vehicle, 150mg/kg/day, 450mg/kg/day. After the indicated tumors were harvested and genomic DNA was extracted and analyzed by the Illumina 450k Methylation array.
2013-04-04 | E-GEOD-45198 | biostudies-arrayexpress