Bb0cb010-4f14-4cff-ba0c-956391463844 - samples
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ABSTRACT:
PROVIDER: EGAD00001011276 | EGA |
REPOSITORIES: EGA
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Project description:Background: Less than 5% of glioblastoma multiforme (GBM) patients survive more than 5-years (long-term survivors, LTS). Nevertheless, the molecular fingerprint of LTS remains uncharted. We aimed to characterize LTS by clinicopathological assessment, DNA methylation (DNAm)/Copy Number Variation (CNV) and mutation profiling. Methods: This multicentric project proposed by Alliance Against Cancer was coordinated by Fondazione IRCCS Istituto Neurologico Carlo Besta. One-hundred forty-two LTS patients were screened, and samples centrally reviewed; 95 patients were enrolled. DNAm profiles and sequencing were performed on 27 LTS and 24 standard survival GBM (STS). Results: We focused on 73 IDHwt-LTS. All patients underwent at least partial resection, followed by Stupp protocol (48/70). The median time to progression was 43 months (4-186), and almost all received a second treatment. Morphological and routine diagnostic molecular features of LTS did not deviate from the classic findings. MGMT promoter methylation was detected in 92% of cases. No significant differences were observed between LTS and STS in terms of prevalence of mutated genes, with TP53 as the most commonly mutated gene (26% of all samples). DNAm showed a more heterogeneous group for LTS, with several cases classified as pediatric high-grade glioma and peculiar CNVs. We identified 18 differentially methylated regions, 4 associated with survival probability (NR2F2, MME, WDR66 and ENPP4). Methylation levels of individual probes in IGFBP3 gene and corresponding protein expression showed a significant correlation with survival. Conclusions: We found no significant different morphology nor mutational profile of LTS. DNAm confirmed as a valuable tool for GBM classification. No specific episignature was detected, but methylation levels of specific genes had prognostic value in LTS.
2024-03-31 | GSE230770 | GEO
Project description:In this study, we investigate how knockdown of the RNA-binding protein TDP-43 alters the transcriptional program of BV2 microglial cells. Aberrant TDP-43 function is a hallmark of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), and while most research has focused on neurons, emerging evidence points to a critical role for microglia in modulating neuroinflammation and disease progression. We employed RNA interference to specifically deplete TDP-43 in BV2 cells (TDP-43 RNAi) and compared them to cells treated with a non-silencing control siRNA. After 24 hours of knockdown, total RNA was isolated. Libraries were prepared from 500 ng of total RNA using the SEQuoia Complete Stranded RNA Library Prep Kit with ribosomal depletion using the SEQuoia Ribodepletion Kit, capturing both long and short RNA species (mRNAs, tRNAs, and other noncoding transcripts). Libraries were assessed on an Agilent 2100 Bioanalyzer (mean insert size ~300 bp) and quantified on a Quantus fluorometer with the QuantiFluor dsDNA System. Sequencing was performed as single-end 75 bp reads on an Illumina NovaSeq 6000 to a depth of ~50 million reads per library. This workflow allows us to pinpoint pathways and gene networks regulated by TDP-43 in microglia.
2025-07-21 | E-MTAB-15184 | biostudies-arrayexpress
Project description:To screen differentially expressed circRNAs in GBM, we performed RNA-seq using four tumor tissues from patients with GBM and four normal brain tissues and focused on circ_0021350, which is upregulated in GBM.
2024-01-10 | GSE222421 | GEO
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
Project description:We performed RNA-seq on HeLa cells to assess the shared transcriptomics changes between USP10 and TDP-43 overexpression, as well as to understand the effect of USP10 overexpression on TDP-43 loss-of-function targets.
2025-09-21 | E-MTAB-15564 | biostudies-arrayexpress
Project description:To investigate the differences in DNA binding specificity of wild-type SALL4 C2H2 zinc finger cluster 4 (ZFC4) and disease causing mutations in SALL4 ZFC4, we performed SELEX coupled with high-throughput sequencing (HT-SELEX) using the purified wild-type SALL4 ZFC4 domain, mutated SALL4 ZFC4 (R900W) and mutated SALL4 ZFC4 (G921D) combined with no protein control experiment.
2023-01-04 | E-MTAB-11519 | biostudies-arrayexpress
Project description:Glioblastoma (GBM) is an aggressive brain tumor that inevitably recurs after radiation therapy, resulting in poor patient outcomes. Given GBM’s cellular heterogeneity, we hypothesized that radiation induces sub-population specific alterations to survive and adapt to radiation stress. We performed integrated single-cell RNA-seq and ATAC-seq analyses across multiple GBM models exposed to clinically relevant radiation doses. Radiation reshaped the cellular landscape, altering both cell type composition and GBM subtype distribution. Cluster-specific and shared transcriptional programs were induced in a dose-dependent manner, with differentially expressed genes enriching distinct biological pathways. Chromatin accessibility analyses revealed parallel cluster-specific remodeling, with both opening and closing of regulatory elements linked to functional pathway shifts. Notably, 2 Gy and 6 Gy exposures elicited conserved transcriptional profiles in RNA clusters across independent GBM lines. Together, these results highlight radiation-induced transcriptional and chromatin remodeling programs in GBM at single-cell resolution and identify conserved cluster-specific adaptations that may underlie therapeutic resistance.
2026-02-16 | GSE309579 | GEO
Project description:Brain tumors (BTs), including glioblastoma (GBM) and meningioma (MGM), contribute significantly to the global cancer burden. The microbiome has been implicated in carcinogenesis, yet its role in BTs remains underexplored. We performed 16S rRNA gene sequencing of the gut microbiota (GM) and intratumoral microbiome (ItM) from fresh tissue samples of 9 patients with GBM and 18 with MGM. 12 age- and sex-matched healthy controls (HCs) were also enrolled. GM profiling revealed reduced alpha diversity and distinct microbial communities in BT patients versus HCs. Notably, Verrucomicrobiota and Synergistaceae were enriched, while Lachnospiraceae, Peptostreptococcaceae, and Muribacter spp. were depleted. GBM patients showed reductions in Peptostreptococcaceae and the Eubacterium hallii group, while MGM patients had increased Synergistia and Erysipelatoclostridium. Compared with MGM, GBM patients were enriched in Peptostreptococcales–Tissierellales, Coprobacillus, and Peptoniphilus but depleted in Weissella. Venn analysis revealed 176 genera shared across groups with unique taxa distinguishing tumor patients and HCs. ItM profiling revealed enrichment of Proteobacteria, Actinomycetota, and Campylobacterota in GBM, while MGM contained higher levels of Bacillota and Bacteroidota. GBM tissues harbored Burkholderia-Caballeronia-Paraburkholderia, Helicobacter, and Leifsonia, whereas MGM tissues were dominated by Bacteroides and Blautia. Notably, stool and tumor samples shared 91 genera in GBM and 105 in MGM. This study provides novel insights by (i) characterizing ItM from fresh samples, (ii) comparing ItM profiles of GBM and MGM, (iii) linking GM and ItM within the same patients, and (iv) suggesting potential clinical implications for BT management.
2025-12-04 | GSE303995 | GEO
Project description:Cross-linking and immunoprecipitation coupled with high-throughput sequencing was used to identify binding sites within 6,304 genes as the brain RNA targets for TDP-43, an RNA binding protein which when mutated causes Amyotrophic Lateral Sclerosis (ALS). Use of massively parallel sequencing and splicing-sensitive junction arrays revealed that levels of 601 mRNAs are changed (including Fus/Tls, progranulin, and other transcripts encoding neurodegenerative disease-associated proteins) and 965 altered splicing events are detected (including in sortilin, the receptor for progranulin), following depletion of TDP-43 from adult brain with antisense oligonucleotides. RNAs whose levels are most depleted by reduction in TDP-43 are derived from genes with very long introns and which encode proteins involved in synaptic activity. Lastly, TDP-43 was found to auto-regulate its synthesis, in part by directly binding and enhancing splicing of an intron within the 3’ untranslated region of its own transcript, thereby triggering nonsense mediated RNA degradation. RNAseq in control and Tdp-43 knockdown mouse striatum
2011-03-03 | E-GEOD-27218 | biostudies-arrayexpress
Project description:Characterization of non-neoplastic and malignant human stem cell populations in their native state can provide new insights into gliomagenesis. Here we developed a purification strategy to directly isolate EGFR+/– populations from human germinal matrix (GM) and adult subventricular zone autopsy tissues, and from de-novo glioblastoma (GBM) resections, enriching for cells capable of binding EGF ligand (LBEGFR+), and uniquely compared their functional and molecular properties. LBEGFR+ populations in both GM and GBM encompassed all sphere-forming cells and displayed proliferative stem cell properties in vitro. In xenografts, LBEGFR+ GBM cells showed robust tumor initiation and progression to high-grade, infiltrative gliomas. Whole transcriptome sequencing analysis confirmed enrichment of proliferative pathways in both developing and neoplastic freshly isolated EGFR+ populations, and identified both unique and shared sets of genes. The ability to prospectively isolate stem cell populations using native ligand-binding ability opens new doors into understanding both normal human progenitors and tumor cell biology.
2017-04-20 | GSE96682 | GEO