Ontology highlight
ABSTRACT:
PROVIDER: PRJNA638264 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The outcome of patients with anaplastic gliomas varies considerably depending on histology and single molecular markers such as codeletion of 1p/19q and mutations of the isocitrate dehydrogenase (IDH) gene. Whether a molecularly-based classification of anaplastic gliomas based on large scale genomic or epigenomic analyses is superior to histopathology, may reflect distinct biological subtypes, predict outcome and guide therapy decisions had yet to be determined. Epigenome-wide DNA methylation analysis, which also allows for the detection of copy-number aberrations, was performed in a cohort of 228 patients with anaplastic gliomas (astrocytomas, oligoastrocytomas and oligodendrogliomas), including 115 patients of the NOA-04 trial. We further compared these tumors with a group of 55 glioblastomas. Unsupervised clustering demonstrated two main groups based on IDH mutation status: CpG island methylator phenotype (CIMP) positive (77.5%) or negative (22.5%). CIMP+ (IDH mutant) tumors showed a further separation based on copy-number status of chromosome arms 1p and 19q, but not based on histopathology. CIMP- (IDH wild type) tumors on the other hand showed hallmark copy-number alterations of glioblastomas. These tumors clustered together with CIMP- glioblastomas without forming separate groups based on WHO grade. There was no Tumor classification based on CIMP and 1p/19q status was significantly associated with survival allowing a better prediction of outcome than the current histopathological classification alone: Patients with CIMP+ tumors with 1p/19q codeletion had the best prognosis, followed by patients with CIMP+ but intact 1p/19q status. Patients with CIMP- anaplastic gliomas had the worst prognosis. Collectively, our data suggest that anaplastic gliomas can be grouped into three molecular subtypes with clear association to underlying biology and clinical outcome based on IDH and 1p/19q status. The data do not provide a molecular basis for the diagnosis of anaplastic oligoastrocytoma. We investigated a subset of 228 anaplastic gliomas using the Illumina 450k methylation array.
2014-06-06 | E-GEOD-58218 | biostudies-arrayexpress
Project description:Genome wide DNA methylation profiling of IDH-wildtype, H3-wildtype AYA glioblastomas
2022-02-12 | GSE196490 | GEO
Project description:The outcome of patients with anaplastic gliomas varies considerably depending on histology and single molecular markers such as codeletion of 1p/19q and mutations of the isocitrate dehydrogenase (IDH) gene. Whether a molecularly-based classification of anaplastic gliomas based on large scale genomic or epigenomic analyses is superior to histopathology, may reflect distinct biological subtypes, predict outcome and guide therapy decisions had yet to be determined. Epigenome-wide DNA methylation analysis, which also allows for the detection of copy-number aberrations, was performed in a cohort of 228 patients with anaplastic gliomas (astrocytomas, oligoastrocytomas and oligodendrogliomas), including 115 patients of the NOA-04 trial. We further compared these tumors with a group of 55 glioblastomas. Unsupervised clustering demonstrated two main groups based on IDH mutation status: CpG island methylator phenotype (CIMP) positive (77.5%) or negative (22.5%). CIMP+ (IDH mutant) tumors showed a further separation based on copy-number status of chromosome arms 1p and 19q, but not based on histopathology. CIMP- (IDH wild type) tumors on the other hand showed hallmark copy-number alterations of glioblastomas. These tumors clustered together with CIMP- glioblastomas without forming separate groups based on WHO grade. There was no Tumor classification based on CIMP and 1p/19q status was significantly associated with survival allowing a better prediction of outcome than the current histopathological classification alone: Patients with CIMP+ tumors with 1p/19q codeletion had the best prognosis, followed by patients with CIMP+ but intact 1p/19q status. Patients with CIMP- anaplastic gliomas had the worst prognosis. Collectively, our data suggest that anaplastic gliomas can be grouped into three molecular subtypes with clear association to underlying biology and clinical outcome based on IDH and 1p/19q status. The data do not provide a molecular basis for the diagnosis of anaplastic oligoastrocytoma.
2014-06-06 | GSE58218 | GEO
Project description:This dataset includes IDAT files from 6 IDH-mutant, 5 IDH-wild-type glioma patient samples of unmatched initial and recurrent timepoints profiled using the Illumina Infinium MethylationEPIC Array.
| EGAD00010002157 | EGA
Project description:This dataset includes paired-end fastq files from 6 IDH-mutant, 5 IDH-wild-type glioma patient samples of unmatched initial and recurrent timepoints profiled using single-cell RNA sequencing.
| EGAD00001007772 | EGA
Project description:This dataset includes 914 BAM files from 6 IDH-mutant, 5 IDH-wild-type glioma patient samples of unmatched initial and recurrent timepoints profiled using single-cell reduced-representation bisulfite sequencing.
| EGAD00001007769 | EGA
Project description:To understand the diversity of expression states in IDH-wildtype Glioblastomas, we profiled 24,131 single cells from 28 patients with GBM by single-cell RNA sequencing (7,930 cells by Smartseq2 and 16,201 by 10X).
2019-07-07 | GSE131928 | GEO
Project description:This dataset includes 22 BAM files for tumor tissue and matched normal blood from 6 IDH-mutant, 5 IDH-wild-type glioma patient samples of unmatched initial and recurrent timepoints profiled using whole genome sequencing.
| EGAD00001007771 | EGA
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:Recurrent glioblastoma (GBM) has a grim prognosis, though MGMT promoter methylation and IDH mutation provide a significant survival advantage. The product of IDH mutation, 2-hydroxyglutarate, increases global DNA methylation by inhibiting demethylases. While lower-grade IDH-mutant gliomas demonstrate increased methylation as a result of this process, DNA becomes relatively hypomethylated during progression from low-grade glioma to secondary (IDH-mutant) GBM. Here we show that global DNA hypomethylation also occurs during primary (IDH-wild type) GBM recurrence. Moreover, in a phase I trial of 14 patients with recurrent (IDH-wild type) GBM, we targeted DNA hypomethylation using a methyl donor treatment. In autopsied tumors from patients treated, we observed a global increase in DNA methylation compared to initial tumor. These results suggest that hypomethylation is a marker for recurrence, and its reprogramming represents a potential therapeutic vulnerability.
2021-12-31 | GSE111627 | GEO