Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

DNA methylome evolution and reprogramming in recurrent glioblastoma

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE111627 | GEO | 2021/12/31

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

G0/G1 switch gene 2 modulates gliomagenesis and radiation response

Project description:Glioblastoma multiforme (GBM), a WHO grade IV glioma is the most common and malignant primary cancer of the central nervous system with a grim median survival of 16 to 17 months upon diagnosis. Radiotherapy is the standard first line treatment for newly diagnosed patients with gliomas, but its effectiveness is limited given their intrinsic resistance and propensity for recurrence. Although possible mechanisms have been attributed to GBM resistance to radiation treatments, the molecular mechanisms regulating radiation resistance of GBM are still unclear.

2019-07-23 | GSE86213 | GEO

Longitudinal epigenome analysis of IDH-wildtype glioblastomas from initial and recurrent surgical specimens

Project description:Genome-wide DNA methylation profiling of 226 longitudinally collected IDH-wildtype glioblastoma tumor specimens from 106 patients, consisting of 99 initial treatment-naive resection specimens prior to any radiation or chemotherapy and 127 recurrent post-treatment resection specimens at time of recurrence/progression usually following radiation and/or chemotherapy. These 127 recurrent post-treatment resection specimens were composed of 106 first surgically-treated recurrent specimens, 19 second surgically-treated recurrent specimens, and 2 third surgically-treated recurrent specimens. The Illumina Infinium EPIC 850k version 1.0 Human DNA Methylation Beadchip was used to obtain DNA methylation profiles across approximately 850,000 CpG sites of genomic DNA extracted from formalin-fixed, paraffin-embedded tumor tissue of the 226 IDH-wildtype glioblastomas.

2024-11-19 | GSE279073 | GEO

Genotyping by array of 123 IDH WT glioblastomas

Project description:Glioblastoma (GBM) is the most frequent and most aggressive form of diffuse glioma. The prognosis is very poor, with a median overall survival of 15 months after maximum safe resection and radiochemotherapy.GBM is one of the most genetically unstable cancers. It is characterized by numerous chromosome (chr) copy number alterations (CNA), such as chr 7 gain, chr 9p loss, and chr 10 loss, along with CDKN2A homozygous deletion (chr 9p21) and EGFR amplification (chr 7p11).Chromosome instability (CIN) may be the cause or the consequence of GBM development. In high-grade diffuse gliomas (HGG), CIN may initiate tumorigenesis. To identify recurrent genomic abnormalities in IDH WT glioblastomas, SNP arrays (Illumina 850K CytoSNP) were analyzed for 123 IDH WT GBM cases.

2018-02-27 | E-MTAB-6371 | biostudies-arrayexpress

Intra-Tumor DNA Methylation Heterogeneity in Glioblastoma; Implications for DNA Methylation-based Classification

Project description:Background: A feature of glioblastoma (GBM) is the cellular and molecular heterogeneity, both within and between tumors. This variability results in a risk for sampling bias and potential tumor escape from future targeted therapy. Heterogeneous gene expression within GBM is well documented, but little is known regarding the epigenetic heterogeneity. We therefore aimed to profile the intra-tumor DNA methylation heterogeneity in GBM. Methods: 3-4 biopsies per tumor from spatially separated regions were collected from 12 GBM patients. We performed genome-wide DNA methylation analysis (~850,000 CpG sites) and compared inter- and intra-tumor variation. Results: All samples were classified as GBM IDH wt or IDH mutated by DNA methylation profiling, but the GBM subtype differed within five tumors. Some GBM samples exhibited higher DNA methylation differences within tumors than between, and many CpG sites (mean: 17,000) had different methylation levels within the tumors. Conclusions: We demonstrated that intra-tumor DNA methylation heterogeneity is a feature of GBM. Although all biopsies were classified as GBM IDH wt/mutated by DNA methylation analysis, the assigned subtype differed in samples from the same patient. The observed DNA methylation heterogeneity within tumors is important to consider for methylation-based biomarkers and future improvements in stratification of GBM patients.

2019-02-27 | GSE116298 | GEO

Longitudinal epigenome analysis of IDH-mutant astrocytomas from initial and recurrent surgical specimens

Project description:Genome-wide DNA methylation profiling of 31 IDH-mutant astrocytoma tumor specimens, of which 14 are from initial surgical resections prior to any radiation or chemotherapy and 17 of which are from a second surgical resection at time of recurrence/progression usually following radiation and/or chemotherapy. For 7 patients (#201-#207), there are paired initial and recurrent tumor samples that were analyzed. For the remaining 17 patients, there are 7 (#208-#214) with only an initial tumor sample analyzed and 10 (#215-#224) with only a recurrent tumor sample analyzed. The Illumina Infinium EPIC 850k Human DNA Methylation Beadchip was used to obtain DNA methylation profiles across approximately 850,000 CpG sites of genomic DNA extracted from formalin-fixed, paraffin-embedded tumor tissue of the 31 IDH-mutant astrocytomas.

2024-11-19 | GSE260850 | GEO

Transcriptional profiling of a patient-matched cohort of glioblastoma (IDH-wildtype) for therapeutic target and repurposing drug identification

Project description:Cohort of patient matched initial and recurrent IDH-wt Glioblastoma GBM. Profiled using Clariom D Human array.

2023-05-03 | GSE212067 | GEO

Mutant IDH modulates suppressive myeloid populations in malignant glioma

Project description:RNA-sequencing for myeloid inflammation-related genes was conducted on primary tumor samples from patients with IDH-wildtype glioblastoma (GBM) and grade 4 IDH-mutant astrocytoma (G4IMA). In addition, the IDH-wildtype murine glioma cell line GL261 and a strain of IDH-mutant GL261 were also sequenced using the murine counterpart of the RNA-sequencing myeloid innate immunity panel.

2024-05-29 | GSE268118 | GEO

Expression data from five primary human glioblastomas (frozen surgical resection) and one non-neoplastic adult brain (frozen autopsy tissue)

Project description:DNA hypomethylation could lead to activation of alternate promoters in GBM. We profiled DNA methylation and H3K4me3 genome-wide, and also performed expression and copy number analysis on the same samples In this dataset, we include all expression data obtained for five GBMs and one normal brain. We identified loci with concurrent DNA hypomethylation and H3K4me3 in GBM, and analyzed expression of the nearest gene in the same sample using these data Six total samples were analyzed. Each GBM sample was compared to normal brain to obtain expression changes

2013-08-13 | E-GEOD-49412 | biostudies-arrayexpress

DNA methylation analysis of glioblastomas harboring FGFR3-TACC3 fusions identifies a methylation subclass with better patient survival.

Project description:Genomewide DNA methylation array profiling of 244 gliobastoma and ganglioglioma samples to study FGFR3-TACC3 gene fusions and resolved into a new entity, glioblastoma IDH-wildtype, FGFR3-TACC3 fusion postive methylation outlier group (GBM-F3T3-O). GBM-F3T3-O showed a unique methylation profile and better survival than other glioblastoma patients. The methylation idat profiles were provided here.

2022-05-16 | GSE200647 | GEO

Multidimensional analysis of patient-matched primary and recurrent glioblastoma identifies microglial FCGR1A (CD64) and other FCGRs as contributors of tumor recurrence [seq]

Project description:Introduction: Glioblastoma (GBM) is a lethal brain tumor without effective treatment options. Here, we sought to characterize longitudinal tumor immune microenvironment (iTME) changes in order to find potential actionable targets to prevent GBM-induced immune evasion mechanisms. This study included 15 patient-matched treatment-naïve (primary, pGBM, WHO grade 4) and recurrent (rGBM) IDH1 wild type tumors. Methods:Extracted RNA and proteins from fresh frozen tumor samples from matched pGBM and rGBM were profiled via transcriptomics and proteomics, respectively. Paired formalin-fixed paraffin-embedded tumor samples were processed for spatial transcriptomics analysis.Results: Differentially expressed genes and proteins between pGBM and rGBM were involved in pathways responsible for synapse development and myelination which have been shown to play a role in GBM recurrence. By categorizing patients into short and long time-to-relapse (STTR vs LTTR), and by correlating TTR with gene expression, we detected genes positively or negatively associated with tumor relapse. Expression of FCG receptor and complement system genes such as FCGR1A (CD64), FCGR3A (CD16a) and the complement C3 were negatively correlated with STTR, whereas high expression of DNMT1/3A, and SMARCA4, involved in DNA methylation, were positively correlated with LTTR. Spatial transcriptomic analysis of the tumor cells compartment defined by GFAP expression showed enrichment in the proportion of oligodendrocytes in recurrent tumors in rGBM, whereas CD64-positive myeloid cell compartment showed a switch of quiescent to activated microglia, appearance of B cells and a reduction in macrophage proportion in recurrent tumors with STTR. Conclusion: Our results uncover a role of CD64-expressing myeloid cells, mostly activated microglia, in GBM recurrence and suggest that interfering with these cells may represent a new therapeutic option for preventing GBM relapse.

2024-11-18 | GSE254145 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data