Polysome profiling of a human glioblastoma reveals intratumoral heterogeneity
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ABSTRACT:
PROVIDER: PRJNA534298 | ENA |
REPOSITORIES: ENA
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Project description:Glioblastoma (GBM) is one of the most aggressive cancers, with median survival of less than 2 years. Despite of considerable advance in molecular classification of GBMs, no improvements in therapy have been described. The scenario is further complicated by tumor heterogeneity and the relationship among genetic, transcriptional and functional findings. Classically, gene expression has been evaluated by steady-state mRNA, however, this does not take translational control into consideration, which contributes considerably to the composition of the proteome. In this study, we evaluated the transcriptomic and translatomic signature of a GBM obtained from a single patient focusing in tumor heterogeneity. In a sampling of eight fragments, we investigated the translation rates, mTORC1 and ERK1/2 pathways and identified both total and polysome associated mRNAs. An increased translation rate was observed in fragments with high-grade histological features. High-grade histology was also associated with the expression of genes related to extracellular matrix (ECM) and angiogenesis, in both transcriptomes and translatomes. However, genes associated with epithelial to mesenchymal transition and stress response, were observed only in translatomes from high-grade fragments. Overall, our results demonstrate that isolation of translated mRNA can be used to identify biomarkers and reveal previously unrecognized determinants of heterogeneity in GBMs.
2019-04-24 | GSE130220 | GEO
Project description:Intratumoral heterogeneity (ITH) is a key driver of therapy resistance in glioblastoma (GBM). This study established a five-gene signature-based gITH classifier through multi-omics analysis, demonstrating robust prognostic predictive value. High-gITH tumors exhibited enhanced molecular complexity, with PDLIM4 identified as the central regulator showing strong correlations with stem-like properties and poor clinical outcomes. Functional validation confirmed that PDLIM4 knockdown suppressed ITH and tumor progression. Our work not only establishes a transcriptome-based quantification framework for GBM heterogeneity, but also reveals PDLIM4 as a promising therapeutic target, offering novel precision medicine strategies.
2026-03-27 | GSE325992 | GEO
Project description:A study for intratumoral heterogeneity of glioblastoma
| PRJNA1442795 | ENA
Project description: Not available
| S-EPMC6539516 | biostudies-literature
Project description:Intratumoral heterogeneity (ITH) is a key driver of therapy resistance in glioblastoma (GBM). This study established a five-gene signature-based gITH classifier through multi-omics analysis, demonstrating robust prognostic predictive value. High-gITH tumors exhibited enhanced molecular complexity, with PDLIM4 identified as the central regulator showing strong correlations with stem-like properties and poor clinical outcomes. Functional validation confirmed that PDLIM4 knockdown suppressed ITH and tumor progression. Our work not only establishes a transcriptome-based quantification framework for GBM heterogeneity, but also reveals PDLIM4 as a promising therapeutic target, offering novel precision medicine strategies.
2026-04-02 | GSE326397 | GEO
Project description:A study for intratumoral heterogeneity of glioblastoma [scRNA-seq]
| PRJNA1445196 | ENA
Project description:Intratumoral heterogeneity in cholangiocarcinoma
| PRJEB63091 | ENA
Project description:Neural stem cells (NSCs) in the subventricular zone (SVZ) have been identified as cells-of-origin carrying driver mutations in glioblastoma (GBM), but there is a lack of understanding how a few NSCs with driver mutations chronologically transform into distant tumor with transcriptional heterogeneity. We used single cell RNA sequencing (scRNA-seq) to show the precancerous cells arising from mutation-harboring NSCs emerge prior to tumor formation and lead to intratumoral heterogeneity in our spontaneous, somatic mouse model as well as in patients’ tumor-free SVZ tissues.
2025-04-10 | GSE217892 | GEO
Project description:Copy number analyses of regionally separated intratumoral biopsies of prostate cancers. Intratumoral heterogeneity (ITH) leads to regional biases of the mutational landscape in a single tumor and may influence the single biopsy-based clinical diagnosis and treatment decision. To evaluate the extent of ITH in unifocal prostate cancers (PCAs) that had not been sought, we analyzed multiple regional biopsies from three PCAs using DNA copy number analyses. DNA copy number showed ITH including regional biases in the presentation of a well-known driver of TMPRSS2-ERG fusion. Our analyses identified a substantial level of genetic ITH in unifocal PCAs at the genomic levels, which should be taken into account for the curation of biomarkers in the clinical setting. Four intratumoral biopsies were obtained per tumor for three prostate cancers. Radical prostatectomy tissue from three patients with prostate cancers were obtained. Board-certified pathologists reviewed the hematoxylin&eosin stained sections and identified tumor-rich regions (> 80% purity). We selected four different areas for biopsy that were at least 5mm apart and were comprised of the most common Gleason pattern (the most common histologic patterns with minimal histologic differences). Copy number profiling was performed using Agilent 180K platform according to the manufacturer's protocol.
2014-01-18 | E-GEOD-54185 | biostudies-arrayexpress
Project description:The aim of this study was to investigate the effect of VEGF targeted therapy (sunitinib) on intratumoral heterogeneity (ITH) in metastatic clear cell renal cancer (mRCC). 138 samples from patients with clear cell renal cell carcinoma, including biological replicates of nephrectomy samples. RNA extracted fresh frozen tissue samples.
2015-05-25 | E-GEOD-65615 | biostudies-arrayexpress