Ena-DATASET-IRCR-02-07-2015-09:52:05:548-46 - samples
Ontology highlight
ABSTRACT:
PROVIDER: EGAD00001001424 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:Tumor recurrence following a standard treatment is the major cause of mortality for glioblastoma (GBM) patients. However, insights on the evolutionary process of the tumor have been limited due to the lack of longitudinally sampled cases. Here, we describe our genomic analyses of 38 GBM patients with pre- and post-treatment samples for each individual (78 tumor samples in total; aCGH data were obtained for 36 among the 78). A substantial shift in the landscape of driver alterations was associated with distant appearances of the recurrent tumors from the initial tumor, suggesting that the genomic profile of an initial tumor can mislead targeted therapies for the distant recurrent tumor. In addition, in contrast to the previous work on IDH1-R132H low-grade gliomas, our GBM patients rarely developed hypermutation following the standard treatment, supporting the safety of temozolomide for IDH1-wild type, primary GBMs under the current standard regimen.
2015-10-06 | GSE63035 | GEO
Project description:Development of model systems that recapitulate the molecular heterogeneity observed amongst GBM tumors will expedite the testing of targeted molecular therapeutic strategies for GBM treatment. In this study, we profiled DNA copy number and mRNA expression in 21 independent GBM tumor lines maintained as subcutaneous xenografts (GBMX), and compared GBMX molecular signatures to those observed in GBM clinical specimens derived from The Cancer Genome Atlas (TCGA). The predominant copy number signature in both tumor groups was defined by chromosome-7-gain/chromosome-10-loss, a poor prognosis genetic signature. We also observed, at frequencies similar to that detected in TCGA GBMs genomic amplification and overexpression of known GBM oncogenes such as EGFR, MDM2, CDK6 and MYCN, and novel genes including NUP107, SLC35E3, MMP1, MMP13 and DDX1. The transcriptional signature of GBMX tumors, which was stable over multiple subcutaneous passages, was defined by overexpression of genes involved in M-phase, DNA Replication, and Chromosome organization (MRC) and was highly similar to the poor-prognosis mitosis-and-cell-cycle-module (MCM) in GBM. Assessment of gene expression in TCGA-derived GBMs revealed overexpression of MRC cancer genes AURKB, BIRC5, CCNB1, CCNB2, CDC2, CDK2, and FOXM1, which form a transcriptional network important for G2/M- progression and/or -checkpoint activation. In conclusion, our study supports propagation of GBM tumors as subcutaneous xenografts as a useful approach for sustaining key molecular characteristics of patient tumors, and highlights therapeutic opportunities conferred by this GBMX tumor panel for testing targeted therapeutic strategies for GBM treatment. Keywords: Disease state analysis RNA expression was assessed in 38 samples: 34 GBM xenograft tumors (29 independent tumors with hybridization replicates for 5 tumors) and 4 non-neoplastic control brain samples
2009-03-07 | E-GEOD-14805 | biostudies-arrayexpress
Project description:Glioblastoma multiforme (GBM) is the most aggressive malignant primary brain tumor with a dismal mean survival even with the current standard of care. Although in vitro cell systems can provide mechanistic insight into the regulatory networks governing GBM cell proliferation and migration, clinical samples provide a more physiologically relevant view of oncogenic signaling networks. However, clinical samples are not widely available and may be embedded for histopathologic analysis. With the goal of accurately identifying activated signaling networks in GBM tumor samples, we investigated the impact of embedding in optimal cutting temperature (OCT) compound followed by flash freezing in LN2 vs. immediate flash freezing (iFF) in LN2 on protein expression and phosphorylationmediated signaling networks. Quantitative proteomic and phosphoproteomic analysis of 8 pairs of tumor specimens revealed minimal impact of the different sample processing strategies and highlighted the large inter-patient heterogeneity present in these tumors. Correlation analyses of the differentially processed tumor sections identified activated signaling networks present in selected tumors and revealed the differential expression of transcription, translation, and degradation associated proteins. This study demonstrates the capability of quantitative mass spectrometry for identification of in vivo oncogenic signaling networks from human tumor specimens that were either OCT-embedded or immediately flash-frozen.
2014-07-09 | PXD001038 | Pride
Project description:Medulloblastomas (MBs) and Glioblastomas (GBMs) are high-incidence central nervous system tumors. Different origin sites and changes in the tissue microenvironment have been associated with onset and progression. Here, we describe differences between the ECM signature of these tumors. We compared the proteomic profiles of MB and GBM decellularized tumor samples among each other and their normal decellularized brain site counterparts. Our analysis reveals that 19 proteins were differentially expressed in MBs, 28 proteins in GBMs, and 11 proteins in both MBs and GBMs. Next, we validated key findings by protein tissue array with 53 MB and 55 GBM cases and evaluated the clinical relevance of the identified differentially expressed proteins through their analysis on publicly available datasets, 763 MB samples from microarray-GSE50161, and 115 GBM samples from RNAseq-TCGA. We report a shift towards a denser fibrillary ECM as well as a clear alteration in the glycoprotein signature, which influences the tumor pathophysiology.
2021-12-30 | PXD023350 | Pride
Project description:Glioblastomas (GBMs), which are the most deadly malignant brain tumors of children and adults, infiltrate the brain and grow rapidly, and are resistant to current therapies. Glioblastomas (GBMs) frequently display mutations that activate receptor tyrosine kinases (RTKs), such as EGFR, which are thought to cooperate with additional factors to drive tumorigenesis. To identify and characterize genetic pathways that cooperate with RTKs to drive GBM progression, we performed RNA sequencing on several cell cultures created from surgical specimens from tumors with alterations in RTKs, and these cultures were grown as neurospheres in serum-free media used for normal neural stem/progenitor cell cultures. Under these conditions, GBM cells retain many defining features and mutations found in primary tumors. For comparison, we profiled commercially available human normal neural stem cells (HNPCs), which were grown under the same conditions. Data from these cell cultures was analyzed for transcripts differentially expressed between GBM cells and HNPCs, which showed that GBM cells that show RTK alterations strongly overexpressed the PDGFA and IGF2 secreted factors, which likely cooperate with EGFR to drive tumor progression.
2018-11-20 | GSE122679 | GEO
Project description:We expanded our previous collection of longitudinal GBM patients (EGAS00001001041) by recruiting 21 additional patients. Tumor specimens were subjected to whole-exome sequencing (16 of 21 cases, with the matched normal/blood) and transcriptome sequencing (16 of 21 cases).
| EGAD00001002143 | EGA
Project description:Transcriptional profiling of major types of B-cell NHL clinical samples. While comparing all the types together, their expression was compared against reactive lymph nodes, except SMZL whose expression was compared against normal splenic cells. Keywords: disease state analysis Clinical samples; 8 reactive lymph nodes, 5 splenic controls Vs 187 cases (38 MCL, 38 CLL, 9 BL, 27 SMZL, 36 DLBCL, 33 FL , 6 nMZL)
2010-05-26 | E-GEOD-9327 | biostudies-arrayexpress
Project description:G protein-coupled receptor 56 (GPR56/ADGRG1) is an adhesion GPCR with an essential role in brain development and cancer. Elevated expression of GPR56 was observed in the clinical specimens of Glioblastoma (GBM), a highly invasive primary brain tumor. However, we found the expression to be variable across the specimens, presumably due to the intratumor heterogeneity of GBM. Therefore, we re-examined GPR56 expression in public domain spatial gene expression data and single-cell expression data for GBM, which revealed that GPR56 expression was high in cellular tumors, infiltrating tumor cells, and proliferating cells, low in microvascular proliferation and peri-necrotic areas of the tumor, especially in hypoxic mesenchymal-like cells. To gain a better understanding of the consequences of GPR56 downregulation in tumor cells and other molecular changes associated with it, we generated a sh-RNA-mediated control and GPR56 knockdown in the GBM cell line U373 and performed transcriptomics, proteomics, and phospho-proteomics analysis and using the data we propose a putative model to explain this functional and regulatory relationship of the two proteins.
2022-05-04 | PXD031569 | Pride
Project description:Molecular profiling of cerebral gliomas distinguishes biologically distinct tumor groups and provides prognostically relevant information beyond histological classification and IDH1/2 mutation status. We performed microarray-based genome- and transcriptome-wide molecular profiling of primary tumor samples from 137 patients with cerebral gliomas, 61 WHO grade II and 76 WHO grade III tumors. For this study, we screened prospectively recruited patients with a histopathological reference diagnosis of cerebral tumors of WHO grade II and III, known KPS at diagnosis, information on extent of resection by early postoperative neuroimaging, available frozen tissue specimens from the initial operation, and documented clinical outcome.
2015-04-30 | E-GEOD-61374 | biostudies-arrayexpress