Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE116298 | GEO | 2019/02/27

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

DNA methylome evolution and reprogramming in recurrent glioblastoma

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

Spatial architecture of high-grade glioma reveals tumor heterogeneity within distinct domains

Project description:High-grade gliomas are aggressive primary brain cancers with poor response to standard regimens, driven by immense heterogeneity. In isocitrate dehydrogenase (IDH) wild-type high-grade glioma (glioblastoma, GBM), increased intra-tumoral heterogeneity is associated with more aggressive disease. Recently, spatial technologies have emerged to dissect this complex heterogeneity within the tumor ecosystem by preserving cellular organization in situ. Here, we construct a high- resolution molecular landscape of GBM and IDH-mutant high-grade glioma patient samples to investigate the cellular subtypes and spatial communities that compose high-grade glioma using digital spatial profiling and spatial molecular imaging. This uncovered striking diversity of the tumor and immune microenvironment, that is embodied by the heterogeneity of the inferred copy- number alterations in the tumor. Reconstructing the tumor architecture revealed brain-intrinsic niches, composed of tumor cells reflecting brain cell types and microglia; and brain-extrinsic niches, populated by mesenchymal tumor cells and monocytes. We further reveal that cellular communication in these niches is underpinned by specific ligand-receptor pairs. This primary study reveals high levels of intra-tumoral heterogeneity in high-grade gliomas, associated with a diverse immune landscape within spatially localized regions.

2023-12-13 | GSE232469 | GEO

Transcription profiling by array of human Glioblastoma multiforme (GBM) tumor samples to asses the intra-tumoral heterogeneity at the gene expression level

Project description:Glioblastoma multiforme (GBM) is a highly heterogeneous disease that shows an enourmous range of genetic abnormalities in comparison to other astrocytic tumors. Intra-patient heterogeneity in GBM has been poorly characterized both at phenotypic and genomic level. During surgical GBM resections, we have extracted between 4 and 8 tumor subsamples from different areas of the malignant tissue that were at least 1cm apart. Our aim to asses the intra-tumoral heterogeneity at the gene expression level to uncover important dynamics underlying GBM progression that may have relevant implication for treatment.

2013-02-16 | E-MTAB-1129 | biostudies-arrayexpress

Infinium EPIC Array data for desmoid tumors

Project description:Desmoid tumors are bland fibroblastic tumors with little histologic variation in different regions of the tumor. While desmoid tumors do not metastasize, they have a high rate of local recurrence after complete resection and no reliable predictors of clinical behavior exist. The presence of molecular intra- and inter-tumor heterogeneity has been well established in other, higher grade, sarcomas but little is known about molecular variability within histologically bland lesions. In this study, we sought to examine the extent of intra- and inter-tumoral clonal heterogeneity of desmoid tumors, which may contribute to their pathogenesis and possible relapse. We performed analysis of DNA methylation, DNA copy number alterations, point mutations and gene expression on 24 specimens from different areas from primary and recurrent desmoid tumors from 3 patients (7-9 specimens per patient). The studies showed a remarkable heterogeneity of DNA methylation, DNA copy number alterations, point mutations or gene expression in different regions in primary or recurrent tumors in each patient. We discovered the evidence for subclonal alterations in different areas of individual tumors. Among the four types of data, the transcriptomic profiles showed the highest degree of variability within tumors and between different tumors from the same patient. Gene expression signatures associated with favorable and unfavorable outcome were detected in different regions within the same tumor. This study shows an unexpected degree of intra- and inter-tumor heterogeneity in desmoid tumors. Our analysis indicates that even in this histologically monotonous lesion, molecular analysis of a single tumor biopsy may underestimate the magnitude of molecular alterations. We demonstrate that molecular intra- and inter-tumor heterogeneity is an important consideration in drug development and validation of prognostic and predictive biomarkers for these tumors.

2024-09-29 | GSE250403 | GEO

OncoScan™ CNV FFPE Assay data for desmoid tumors

2024-09-29 | GSE250149 | GEO

Profiling by array of human Glioblastoma multiforme (GBM) tumor samples to asses the intra-tumoral heterogeneity in genomic copy number aberrations

Project description:Glioblastoma multiforme (GBM) is a highly heterogeneous disease that shows an wide range of genetic abnormalities in comparison to other astrocytic tumors. We have extracted between 4 and 8 tumor subsamples from different areas of the malignant tissue that were at least 1cm apart. Our aim to asses the intra-tumoral heterogeneity by comparing copy number aberrations in different tumor areas to uncover important dynamics underlying GBM progression.

2013-02-15 | E-MTAB-1215 | biostudies-arrayexpress

Single-cell landscapes of primary glioblastomas and matched organoids and cell lines reveal variable retention of inter- and intra-tumor heterogeneity [multi-generation scRNA-seq]

Project description:Glioblastomas (GBMs) are aggressive primary malignant brain tumors characterized by extensive levels of inter- and intra-tumor genetic and phenotypic heterogeneity. Patient-derived organoids (PDOs) have recently emerged as useful models to study such heterogeneity. Here, we present bulk exome as well as single-cell genome and transcriptome profiles of primary IDH wild type GBMs from ten patients, including two recurrent tumors, as well as PDOs and brain tumor-initiating cell (BTIC) lines derived from these patients. We find that PDOs are genetically similar to and variably retain gene expression characteristics of their parent tumors. At the phenotypic level, PDOs appear to exhibit similar levels of transcriptional heterogeneity as their parent tumors, whereas BTIC lines tend to be enriched for cells in a more uniform transcriptional state. The datasets introduced here will provide a valuable resource to help guide experiments using GBM-derived organoids, especially in the context of studying cellular heterogeneity.

2022-02-16 | GSE193884 | GEO

Single-cell landscapes of primary glioblastomas and matched organoids and cell lines reveal variable retention of inter- and intra-tumor heterogeneity [scRNA-seq]

2022-02-16 | GSE173278 | GEO

Single-cell landscapes of primary glioblastomas and matched organoids and cell lines reveal variable retention of inter- and intra-tumor heterogeneity [scWGS]

2022-02-16 | GSE173279 | GEO

Multiregional sampling of primary glioblastoma specimens

Project description:Glioblastoma (GBM), the most common malignant tumor originating in the brain remains incurable with few treatment advances despite decades of investigation. Treatment failure is often attributed to intratumoral heterogeneity, which fosters tumor evolution and selection of resistant clones. However, intratumoral heterogeneity and tumor evolution remain poorly understood in GBM as studies are typically based on single tissue biopsies and lack spatial context. Here, we have utilized pre-operative MRI scans and intra-operative 3-D surgical neuronavigation for 10 primary IDH-WT GBM patients to acquire 103 tissue samples that represent maximal tumor diversity and are mapped by 3-D spatial coordinates. We combine insights from deconvolution of GBM transcriptomes and chromatin landscapes with single-cell analysis to assess intratumoral heterogeneity of each program at the cellular level and to distinguish neuronal, glial, and immune programs aberrantly active in tumor cells from their counterparts in normal cells. Collectively, these data provide unprecedented insight into GBM intratumoral heterogeneity and evolution from single-cell to whole-tumor 3D spatial resolution, redefining current understanding and providing a rich resource of targets for therapeutic investigation.

2024-01-18 | GSE226726 | 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