PMCDS000ABE - samples
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ABSTRACT:
PROVIDER: EGAD00001010282 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:Ither NB in Organoids WXS dataset - We aimed to launch an online repository integrating genomics and transcriptomics with high-throughput drug screening (HTS) of nineteen commonly used neuroblastoma cell lines and fourteen generated neuroblastoma patient-derived organoids (NBL-PDOs) to improve identification of molecularly matched therapies and support clinical uptake.
| EGAD00001010281 | EGA
Project description:Ither NB in Organoids RNA-Seq dataset - We aimed to launch an online repository integrating genomics and transcriptomics with high-throughput drug screening (HTS) of nineteen commonly used neuroblastoma cell lines and fourteen generated neuroblastoma patient-derived organoids (NBL-PDOs) to improve identification of molecularly matched therapies and support clinical uptake.
| EGAD00001010283 | EGA
Project description:Despite druggable events in 80% of neuroblastoma patients within the Princess Máxima Center precision medicine program 'iTHER', clinical uptake of treatment recommendations has been low, and the clinical impact for individual patients remains hard to predict. This stresses the need for a method integrating genomics and transcriptomics with functional approaches into therapeutic decision making.
We aimed to launch an online repository integrating genomics and transcriptomics with high-throughput drug screening (HTS) of nineteen commonly used neuroblastoma cell lines and fourteen generated neuroblastoma patient-derived organoids (NBL-PDOs) to improve identification of molecularly matched therapies and support clinical uptake. Cell lines, NBL-PDOs and their parental tumors were characterized utilizing (lc)WGS, WES and RNAseq. Cells were exposed to a ~200 compound library, and viability was assessed using CellTiterGlo or MTT. Molecular and HTS results were transferred to the R2 platform (http://r2platform.com/pmc_nb_drugs/), in which a comprehensive suite of visualizations and analysis options were implemented.
As a result, a powerful reference set of cell lines is available, reflecting distinct known pharmacologic vulnerabilities, including resistance of TP53-inactivated lines to MDM2 inhibitor idasanutlin; ALK-inhibitor sensitivity in ALK-activated lines, and sensitivity of an ATM-deleted cell line to PARP- and CHEK1-inhibitors. Novel established NBL-PDOs retained molecular features of their parental tumor and again reflected established drug sensitivities. However, HTS also identified additional therapeutic vulnerabilities in vitro, such as a striking correlation between a positive mesenchymal signature and sensitivity to BCL2-inhibitor venetoclax. Finally, we explored personalized drug sensitivities within iTHER, demonstrating HTS can support genomic and transcriptomic results, thereby strengthening the rationale for clinical uptake. Furthermore, in vitro insensitivity may avoid ineffective treatments. Lastly, novel treatment options may be identified, as indicated by sensitivity to ponatinib correlating with overexpression of RET or KIT.
In conclusion, we established a dynamic publicly available dataset with detailed genomic, transcriptomic, and pharmacological annotation of classical neuroblastoma cell lines as well as NBL-PDOs, representing the heterogeneous landscape of neuroblastoma. We anticipate that in vitro drug screening will be complementary to genomic-guided precision medicine by supporting clinical decision making, thereby improving prognosis for all neuroblastoma patients in the future.
| EGAS00001007160 | EGA
Project description:High anaplastic lymphoma kinase (ALK) protein levels may be correlated with an unfavorable prognosis in neuroblastoma (NBL) patients, regardless of ALK mutation status. We therefore examined the correlation between levels of ALK, phosphorylated ALK (pALK) and downstream signaling proteins and response to ALK inhibition in a large panel of both ALK mutated (MUT) and wild type (WT) NBL cell lines. Six of the nineteen NBL cell lines had a point mutation and four an amplification of the ALK gene. ALK amplified cell lines showed similar ALK levels and ALK inhibitor sensitivity as WT cell lines and were therefore co-analyzed. The ALK mRNA (p=0.043), ALK 220 kDa (p=0.009) and ALK 140 kDa (p=0.025) protein levels were higher in ALK mutant (n=6) than WT cell lines (n=13). ALK mRNA and protein levels significantly correlated with ERK1 and ERK2 protein levels, and also with PHOX2B mRNA levels, a neural differentiation marker which is mutated in NBL. Response to ALK inhibitor TAE684 was also significantly correlated with ALK levels. ALK mutant cell lines (n=4) demonstrated a higher sensitivity towards ALK inhibitor TAE684 (14.9 fold more sensitive, p=0.004) than eight WT cell lines. These results underline the importance of ALK mutations but also ALK levels for response to ALK inhibitors in NBL cell lines. Furthermore, the strong correlation of PHOX2B and ALK suggests that neural differentiation stage may be correlated with ALK levels in neuroblastoma. These data will enhance understanding of ALK inhibitor response in future patient trials. To study differentially expressed genes in the neuroblastoma cell lines described in the protein analysis study above, 15 cell lines and 2 derivative cell lines were used.
2011-07-07 | E-GEOD-22771 | biostudies-arrayexpress
Project description:Neuroblastoma (NB) is a pediatric cancer characterized by significant heterogeneity and poor prognosis, especially in high-risk cases with MYCN amplification. Understanding the molecular response of neuroblastoma to different treatments can provide insights into potential therapeutic strategies. The aim of the experiment was to evaluate the effects of treatment of pitavastatin (PIT), prochloperazine (PCZ) and combination (PIT + PCZ) on LU-NB-2 PDX derived organoid model. In our experiments we observed synergistic effects on cell viability and cell death of those two compounds and further RNA-seq was intended to decipher effects of the combination on the neuroblastoma cells. Experimental Workflow: Sample Preparation: Tumor organoids were generated from PDX models of high-risk neuroblastoma patients with MYCN amplification. Treatment: LU-NB-2 PDX organoids were dissociated to single cells aseeded in T25 flasks, allowed to grow for 24 h, and treated for 48 h with the combination of PCZ +PIT (1.6 µM and 6.7 µM, n = 8), PCZ only (1.6 µM, n = 8), PIT only (6.7 µM, n = 8), or DMSO (n = 8). The treatment resulted in a ~15% decrease in NB cell viability in the combination group. RNA Extraction: Total RNA was extracted from the treated and control organoids. Library Preparation and Sequencing: RNA-seq libraries were prepared and sequenced to generate high-throughput sequencing data. Data Analysis: Differential gene expression analysis was performed to compare the treated samples against the untreated controls, aiming to elucidate the molecular effects of each treatment.
2025-05-25 | E-MTAB-14846 | biostudies-arrayexpress
Project description:High anaplastic lymphoma kinase (ALK) protein levels may be correlated with an unfavorable prognosis in neuroblastoma (NBL) patients, regardless of ALK mutation status. We therefore examined the correlation between levels of ALK, phosphorylated ALK (pALK) and downstream signaling proteins and response to ALK inhibition in a large panel of both ALK mutated (MUT) and wild type (WT) NBL cell lines. Six of the nineteen NBL cell lines had a point mutation and four an amplification of the ALK gene. ALK amplified cell lines showed similar ALK levels and ALK inhibitor sensitivity as WT cell lines and were therefore co-analyzed. The ALK mRNA (p=0.043), ALK 220 kDa (p=0.009) and ALK 140 kDa (p=0.025) protein levels were higher in ALK mutant (n=6) than WT cell lines (n=13). ALK mRNA and protein levels significantly correlated with ERK1 and ERK2 protein levels, and also with PHOX2B mRNA levels, a neural differentiation marker which is mutated in NBL. Response to ALK inhibitor TAE684 was also significantly correlated with ALK levels. ALK mutant cell lines (n=4) demonstrated a higher sensitivity towards ALK inhibitor TAE684 (14.9 fold more sensitive, p=0.004) than eight WT cell lines. These results underline the importance of ALK mutations but also ALK levels for response to ALK inhibitors in NBL cell lines. Furthermore, the strong correlation of PHOX2B and ALK suggests that neural differentiation stage may be correlated with ALK levels in neuroblastoma. These data will enhance understanding of ALK inhibitor response in future patient trials.
2011-07-07 | GSE22771 | GEO
Project description:Neuroblastoma (NB) is a pediatric cancer characterized by significant heterogeneity and poor prognosis, particularly in high-risk cases with MYCN amplification. Understanding the molecular response of neuroblastoma to different treatments can provide valuable insights into potential therapeutic strategies. This experiment assessed the in vivo response to treatment with BAY390 and A967079. A neuroblastoma in vivo model was established via subcutaneous injection of human high-risk, MYCN-amplified neuroblastoma organoids into female NSG mice (PDX, LU-NB-3R). Once tumors reached 150 mm³, mice were randomized into treatment groups: control (n=8), A967079 (n=6), and BAY390 (n=7). All drugs were administered via oral gavage at the following concentrations: A967079 (300 mg/kg, once daily) or BAY390 (90 mg/kg, once daily), with a vehicle control group. Treatment was administered for 21 days, after which mice were euthanized. Tumor samples were collected in RNA later and frozen at -80 °C until RNA extraction. RNA was extracted from tumor tissue, and RNA sequencing was performed.
2026-04-01 | E-MTAB-15002 | biostudies-arrayexpress
Project description:Neuroblastoma (NBL) tumors are considered heterogeneous tumors. So far, little detailed information available on their immune environment. We used single cell RNA sequencing (scRNA-seq) to analyze the tumor microenvironment of neuroblastoma.
2023-12-22 | GSE218003 | GEO
Project description:Neuroblastoma (NBL) is an embryonal cancer of the sympathetic nervous system (SNS) that causes 15% of pediatric cancer deaths. High-risk neuroblastoma is characterized by N-Myc amplification and segmental chromosomal gains and losses. Due to limited disease models, the etiology of neuroblastoma is largely unknown, including both the cell of origin and the majority of oncogenic drivers. We have established a novel system for studying neuroblastoma based on the transformation of neural crest cells (NCCs), the progenitor cells of the SNS, isolated from mouse embryonic day 9.5 trunk neural tube explants. Based on pathology and gene expression analysis, we report the first successful transformation of wild-type NCCs into NBL by enforced expression of N-Myc to generate phenotypically and molecularly accurate tumors that closely model human MYCN-amplified NBL. Using comparative genomic hybridization, we found that NCC-derived neuroblastoma tumors acquired copy number gains and losses that are syntenic to those observed in human MYCN-amplified neuroblastoma including 17q gain, 2p gain and loss of 1p36. When p53-compromised NCCs were transformed with N-Myc we generated primitive neuroectodermal tumors with divergent differentiation including osteosarcoma. These subcutaneous tumors were metastatic to regional lymph nodes, liver and lung. Our novel experimental approach accurately models human neuroblastoma and establishes a new system with potential to study early stages of neuroblastoma oncogenesis, to functionally assess neuroblastoma oncogenic drivers, and to characterize neuroblastoma metastasis.
2017-09-25 | GSE94914 | GEO