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Expression Data human IDH1 mutant and wild-type high grade gliomas

ABSTRACT: Expression Data human IDH1 mutant and wild-type high grade gliomas

PROVIDER: PRJNA413642 | ENA |

REPOSITORIES: ENA

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Expression Data human IDH1 mutant and wild-type high grade gliomas

Project description:Gene expression data generated for the purpose of correlating differentially-expressed genes between IDH1 mutant and IDH1 wild-type high grade gliomas with differential hydroxymethylcytosine profiles as determined using Illumina EPIC BeadChip platform.

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Expression data and methylation analysis of IDH1 mutant and wild-type high grade gliomas

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Metabolic changes related to the IDH1 mutation in gliomas preserve TCA-cycle activity: an investigation at the protein level

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

Metabolic changes related to the IDH1 mutation in gliomas preserve TCA-cycle activity: an investigation at the protein level

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Characterization of a diffuse low and high grade glioma cell line biobank

Project description:Diffuse low and high grade glioma are primary brain tumors arising from gllial cells. They are subdivided into three groups: IDH1-mutant oligodendrogliomas, IDH1-mutant astrocytomas and IDH1-Wild Type glioblastomas. Cellular tools to study these tumors remains poors, specially for low grades gliomas. We constituted a biobank of 12 patient-derived cell lines, from IDH1-mutant and wild type gliomas, then charactrized them to test their relevance as in vitro models.

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Autophagy Inhibition Sensitizes Radiotherapy Responses in High-grade Mutant IDH1 Glioma

Project description:Mutant isocitrate dehydrogenase 1 (mIDH1) catalyzes 2-hydroxyglutarate (2-HG) production which leads to epigenetic reprogramming in astrocytomas with TP53/ATRX loss. RNA-sequencing, single-cell RNA-sequencing, and Chromatin Immunoprecipitation sequencing followed by analysis shows that human and mouse mIDH1 gliomas exhibit downregulated gene ontologies (GOs) related to mitochondrial metabolism and upregulated autophagy-related GOs. Decreased mitochondrial metabolism is accompanied by decreased glycolysis, rendering autophagy as a source of energy in mIDH1 gliomas. Mutant IDH1 glioma cells exhibit increased expression of autophagy-related proteins and enhanced LC3 I/II conversion, indicating augmented autophagy. Inhibiting autophagy in vivo by administration of synthetic protein nanoparticles encapsulating autophagy related gene 7 silencing RNA sensitized mIDH1 glioma cells to radiation, resulting in tumor regression, long-term survival, and immunological memory. This work uncovers autophagy as a critical pathway for survival in mIDH1 gliomas and its inhibition elicits radiosensitivity in vitro in human and mouse mIDH1 glioma cells, and in vivo in mIDH1 models.

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High density foci in IDH1-mutated diffuse low-grade gliomas in adults

Project description:20% of patients affected with diffuse low-grade brain tumors have high cell density foci harboring higher KI67 index and DNA alterations. These foci may represent tumor progression towards high-grade gliomas. Here we performed transcriptome analysis of those foci vs adjacent tumoral tissues dissected from formalin fixed and paraffin embedded blocks.

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Gene expression profile at single level of 8 cell lines isolated from IDH1-mutant diffuse glioma tumors

Project description:Diffuse low-grade gliomas are incurable brain tumours that often carry a mutation in the IDH1 gene. These tumours are heterogeneous and have different types of tumour cells. They can progress toward high grade gliomas. To understand the diversity of tumour cells and how they arise, we have performed single RNA seq of 8 cell lines derived from IDH1 mutant patients. Some cell lines maintained the IDH1 mutation while others lost it. We analysed these cultures when growth factors are present or absent for 4 days to promote differentiation.

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High grade glioma methylation analysis using bisulfite and oxidative bisulfite-treatment

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