Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA257898 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:DNA methylation analysis of 68 glioblastoma specimen of patients treated within clinical trials, 5 samples of normal brain tissue (non-tumor brain) and 4 tumor-derived glioma sphere lines. The data was used to identify changes in DNA methylation which contribute to the aberrant of expression of HOX transcription factors. Our group had previously demonstrated that expression of HOX genes was associated with increased resistance to chemo-radiotherapy and worse outcome in GBM patients Keywords: Disease state comparison Bisulphite converted genomic DNA from the 77 samples were hybridised to the Illumina Infinium 450 Human Methylation Beadchip
2015-01-06 | E-GEOD-60274 | biostudies-arrayexpress
Project description:DNA methylation analysis of 68 glioblastoma specimen of patients treated within clinical trials, 5 samples of normal brain tissue (non-tumor brain) and 4 tumor-derived glioma sphere lines. The data was used to identify changes in DNA methylation which contribute to the aberrant of expression of HOX transcription factors. Our group had previously demonstrated that expression of HOX genes was associated with increased resistance to chemo-radiotherapy and worse outcome in GBM patients Keywords: Disease state comparison
2015-01-06 | GSE60274 | GEO
Project description:Glioblastoma (GBM) is a lethal brain tumor without effective treatment options. Data about proteomics in glioma is sparse and it has not yet been integrated into the routine diagnostic work-up or exploited to find potential actionable targets to prevent GBM-induced immune evasion mechanisms and recurrence. We performed proteomic analysis of diffuse glioma samples classified into six subgroups defined by DNA methylation and patient-paired primary and recurrent samples in order to i) provide an inventory of proteins commonly or individually overexpressed in each of the four HGG subgroups compared to the LGG and deduce relevant pathways for each subgroup and ii) identify specific proteins involved in tumor recurrence after surgical removal.
The first study revealed largest differences between low-grade (LGG) and high-grade gliomas (HGG), with major changes observed in proteins involved in active calcium-dependent vesicle trafficking (S100 proteins and annexins), effectors of the immunological synapse, proteins involved in Retinoid acid signalling, and proteins involved in extracellular matrix, cytoskeleton, and cell adhesion. Comparative proteomic analysis between LGG and the HGG subgroups also showed consistency with glioma grading.
The second study identified FcGamma receptors on activated microglia and complement components as major players inducing short relapsing GBM tumors.
In conclusion, specific pathways and proteins represent potential targets to control progression of the distinct subgroups.
2023-04-19 | MSV000091739 | MassIVE
Project description:Glioblastoma (GBM) is the most common lethal primary brain cancer in adults. Despite treatment regimens including surgical resection, radiotherapy, and temozolomide (TMZ) chemotherapy, growth of residual tumor leads to therapy resistance and death. At recurrence, a quarter to a third of all gliomas have hypermutated genomes 5, with mutational burdens orders of magnitude greater than in normal tissue. Here, we quantified the mutational landscape progression in a patient’s primary and recurrent GBM, and uncovered Cas9-targetable repeat elements. We show that CRISPR-mediated targeting of highly repetitive loci enables rapid elimination of GBM cells, an approach we term “Genome Shredding”. Importantly, in the patient’s recurrent GBM, we identified unique repeat sequences with TMZ mutational signature and demonstrate that their CRISPR targeting enables cancer-specific cell ablation. “Cancer Shredding” leverages the non-coding genome and therapy-induced mutational signatures for targeted GBM cell depletion and provides an innovative paradigm to develop treatments for hypermutated glioma.
2023-10-05 | GSE244497 | GEO
Project description:Glioblastoma (GBM) is the most common and most aggressive primary brain tumor in adults. The existence of a small population of stem-like tumor cells that efficiently propagate tumors and resist cytotoxic therapy is one proposed mechanism leading to the resilient behavior of tumor cells and poor prognosis. In this study, we performed an in-depth analysis of the DNA methylation landscape in GBM-derived cancer stem cells (GSCs). Parallel comparisons of primary tumors and GSC lines derived from these tumors with normal controls (a neural stem cell (NSC) line and normal brain tissue) identified groups of hyper- and hypomethylated genes that display a trend of either increasing or decreasing methylation levels in the order of controls, primary GBMs, and their counterpart GSC lines, respectively. Interestingly, concurrent promoter hypermethylation and gene body hypomethylation were observed in a subset of genes including MGMT, AJAP1 and PTPRN2. These unique DNA methylation signatures were also found in primary GBM-derived xenograft tumors indicating that they are not tissue culture-related epigenetic changes. Integration of GSC-specific epigenetic signatures with gene expression analysis further identified candidate tumor suppressor genes that are frequently down regulated in GBMs such as SPINT2, NEFM and PENK. Forced re-expression of SPINT2 reduced glioma cell proliferative capacity, anchorage independent growth, cell motility, and tumor sphere formation in vitro. The results from this study demonstrate that GSCs possess unique epigenetic signatures that may play important roles in the pathogenesis of GBM. The reduced representation bisulfite sequencing (RRBS) approach (Meissner et al., 2008) was used to generate genome-wide single-base resolution CpG methylation profiles of three primary GBMs (1063T, 1133T, and 1142T) and three GSC lines (1063S, 1133S, 1142S) derived from these primary GBM tumors. The NSC line and the normal brain (NB) tissue sample were used as controls for comparison purposes. In addition, we analyzed three GBM xenograft tumor tissue samples (Mayo22, Mayo39, Mayo59) developed by Dr. Jann N. Sarkaria of Mayo Clinic.
2015-06-24 | E-GEOD-70175 | biostudies-arrayexpress
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
Project description:Glioblastoma (GBM) is the most common malignant primary brain tumor and remains incurable. Previous work has shown that systemic administration of Decitabine (DAC) induces sufficient expression of NY-ESO-1 in GBM for targeting by adoptive T-cell therapy in vivo. However, the mechanisms by which DAC enhances immunogenicity in GBM remain to be elucidated. Using patient tissue, immortalized glioma cells, and primary patient-derived gliomaspheres, we demonstrate in vitro that basal NY-ESO-1 expression is restricted by promoter hypermethylation in gliomas. DAC treatment of glioma cells specifically inhibits DNA methylation silencing and renders NY-ESO-1 an inducible tumor antigen. Targeting of DAC-induced NY-ESO-1 in primary GBM cells promotes specific and polyfunctional NY-ESO-1 TCR-T cell responses. DAC further upregulates other tumor-associated cancer testis antigens concomitantly with tumor-intrinsic reactivation of human endogenous retroviruses (hERV) and type I interferon. Overall, we demonstrate that DAC promotes an inducible tumor antigen and enhances T cell functionality against GBM.
2024-06-04 | GSE261190 | GEO
Project description:Glioblastoma (GBM) is the most common malignant primary brain tumor and remains incurable. Previous work has shown that systemic administration of Decitabine (DAC) induces sufficient expression of NY-ESO-1 in GBM for targeting by adoptive T-cell therapy in vivo. However, the mechanisms by which DAC enhances immunogenicity in GBM remain to be elucidated. Using patient tissue, immortalized glioma cells, and primary patient-derived gliomaspheres, we demonstrate in vitro that basal NY-ESO-1 expression is restricted by promoter hypermethylation in gliomas. DAC treatment of glioma cells specifically inhibits DNA methylation silencing and renders NY-ESO-1 an inducible tumor antigen. Targeting of DAC-induced NY-ESO-1 in primary GBM cells promotes specific and polyfunctional NY-ESO-1 TCR-T cell responses. DAC further upregulates other tumor-associated cancer testis antigens concomitantly with tumor-intrinsic reactivation of human endogenous retroviruses (hERV) and type I interferon. Overall, we demonstrate that DAC promotes an inducible tumor antigen and enhances T cell functionality against GBM.
2024-06-03 | GSE261188 | GEO
Project description:Glioblastoma (GBM) is the most common malignant primary brain tumor and remains incurable. Previous work has shown that systemic administration of Decitabine (DAC) induces sufficient expression of NY-ESO-1 in GBM for targeting by adoptive T-cell therapy in vivo. However, the mechanisms by which DAC enhances immunogenicity in GBM remain to be elucidated. Using patient tissue, immortalized glioma cells, and primary patient-derived gliomaspheres, we demonstrate in vitro that basal NY-ESO-1 expression is restricted by promoter hypermethylation in gliomas. DAC treatment of glioma cells specifically inhibits DNA methylation silencing and renders NY-ESO-1 an inducible tumor antigen. Targeting of DAC-induced NY-ESO-1 in primary GBM cells promotes specific and polyfunctional NY-ESO-1 TCR-T cell responses. DAC further upregulates other tumor-associated cancer testis antigens concomitantly with tumor-intrinsic reactivation of human endogenous retroviruses (hERV) and type I interferon. Overall, we demonstrate that DAC promotes an inducible tumor antigen and enhances T cell functionality against GBM.
2024-06-03 | GSE261187 | GEO
Project description:In this study, we developed an extensive dataset for a GBM case via the generation of polyclonal and monoclonal glioma stem cell lines from initial diagnosis, as well as from multiple sections of distant tumor locations of the deceased patient’s brain following tumor recurrence. Our analyses revealed the tissue-wide expansion of a new clone in the recurrent tumor as well as chromosome 7 gain and chromosome 10 loss as repeated genomic events in primary and recurrent disease. Moreover, chromosome 7 gain and chromosome 10 loss produced similar alterations in mRNA expression profiles in primary and recurrent tumors despite possessing other highly heterogeneous and divergent genomic alterations between the tumors. We identified ETV1 and CDK6 as putative candidate genes, and NFKB (complex), IL1B, IL6, Akt and VEGF as potential signaling regulators, as potentially central downstream effectors of chr7 gain and chr10 loss. Finally, the differences caused by the transcriptomic shift following gain of chromosome 7 and loss of chromosome 10 were consistent with those generally seen in GBM samples compared to normal brain in large-scale patient-tumor data sets.
2017-10-01 | GSE101113 | GEO