Project description:This dataset contains gene expression data from the NRC series (Neuroblastoma Research Consortium) for a total of 283 primary neuroblastoma tumors. All tumor samples are fully annotated including patient age at diagnosis, overall and progresison free survival and MYCN amplification status, enabling subgroup analysis, survival analysis and gene expression network analysis.
Project description:Previous studies have reported that metastatic tumor cells acquire genomic aberrations compared to those present in the primary due to an unstable genome. However, it is not clear if all malignancies follow a similar pattern. Neuroblastoma is the most common extra-cranial solid tumor of childhood. To examine how the neuroblastoma genome changes during tumor progression, we investigated chromosomal structural alterations across three tumors from a patient with hisg-risk neuroblastoma. The tumors included the primary tumor, one metastatis collected at diagnosis before any treatment, and a second metastatis collected during post mortem investigation. The recapitulated chromosomal structural alterations demonstrated that all three tumors had extensive chromosomal alterations involving virtually every chromosome. All tumors were aneuploid and shared many chromosomal alterations often seen in neuroblastoma. Despite some tumor to tumor structural variability, approximately 81-91% of the altered regions were shared among the three tumor genomes with primary tumor and pre-treamment metastatis being the most similar. Three samples from one patient with high-risk neuroblastoma. Primary tumor plus two metastatic tumors. One of metastasis sampled at diagnosis, before any treatment, and second metastasis taken at autopsy.
Project description:Neuroblastoma is a solid pediatric tumor with heterogeneous clinical behaviors. Chemotherapy is widely used to treat neuroblastoma. However, dose-dependent responses and chemoresistance mechanisms of neuroblastoma cells to anticancer drugs remain challenges in various conditions. Here, we investigated the dose-dependent effects of topotecan on human neuroblastoma cells (SK-N-SH, SH-SY5Y, and SK-N-BE) under various nutrient supply conditions. Serum-starved human neuroblastoma cells showed reduced toxicity, and their survival rate increased upon treatment with a high concentration (1 μM) of topotecan. Quantitative profiling of global and phosphoproteome identified 12,959 proteins and 48,812 phosphosites, respectively, from SK-N-SH cells. Network analysis revealed that topotecan up-regulated DNA repair and cholesterol-mediated topotecan efflux, resulting in topotecan resistance. Results of DNA damage assay, cell cycle, and quantitative analyses of membrane cholesterol supported the validity of these resistance factors and their applicability to all neuroblastoma cells investigated in this study. Our results provide a model for high dose-dependent chemoresistance in neuroblastoma cells that could enable a patient-dependent chemotherapy screening strategy.
Project description:Our current knowledge of the different immune cells in neuroblastoma is based on in vitro and in vivo studies mainly focusing on a single cell type. Importantly, different studies have conveyed conflicting results. Moreover, a comprehensive immune cell overview at the single-cell level is still missing and understanding the complete immune cell composition of neuroblastoma will be crucial for the development of novel immunotherapeutics against the disease. In this study, we performed single-cell RNA-sequencing on nineteen human neuroblastoma samples coupled with multiplex immunohistochemistry and survival analysis using additional datasets to provide a comprehensive cellular and molecular immune cell landscape of human neuroblastoma. Further, we contrasted our data with single-cell RNA-sequencing data from normal fetal adrenal gland to characterize cell-state changes from normal tissue to cancerous neuroblastoma. Our analysis revealed 27 immune cell subtypes including distinct subpopulations of myeloid, NK, B and T cells not identified in neuroblastoma before. Several immune cell subtypes demonstrated a survival benefit such as inflammatory monocytes, tumor associated macrophages, various T cell populations, and Active NK cells. Furthermore, in contrast to adult cancers and previous neuroblastoma studies, we demonstrated an increase in inflammatory monocyte cell-state when contrasting normal and tumor tissue, while we do not observe differences in cytotoxicity and exhaustion score for cytotoxic T cells, nor in Treg activity. Finally, we performed a systemic receptor-ligand interaction analysis between tumor, stroma and immune cells, where we showed the neuroblastoma tumor microenvironment is highly complex and strongly correlated to survival. In addition, we highlighted several interactions that we suggest to be tested in future studies as a therapeutic option in human neuroblastoma. Taken together, our study significantly adds to the in depth understanding of the immune cell landscape, the complexity of the tumor microenvironment and it provides a resource for the development of novel immunotherapeutics for neuroblastoma.
Project description:Previous studies have reported that metastatic tumor cells acquire genomic aberrations compared to those present in the primary due to an unstable genome. However, it is not clear if all malignancies follow a similar pattern. Neuroblastoma is the most common extra-cranial solid tumor of childhood. To examine how the neuroblastoma genome changes during tumor progression, we investigated chromosomal structural alterations across three tumors from a patient with hisg-risk neuroblastoma. The tumors included the primary tumor, one metastatis collected at diagnosis before any treatment, and a second metastatis collected during post mortem investigation. The recapitulated chromosomal structural alterations demonstrated that all three tumors had extensive chromosomal alterations involving virtually every chromosome. All tumors were aneuploid and shared many chromosomal alterations often seen in neuroblastoma. Despite some tumor to tumor structural variability, approximately 81-91% of the altered regions were shared among the three tumor genomes with primary tumor and pre-treamment metastatis being the most similar.
Project description:Neuroblastoma (NB) is a common pediatric malignancy tumor with poor outcome. Recent studies show that MDM2 protein inhibitors are promising anti-cancer agents. MI-773 is a novel and specific antagonist of MDM2 and the molecular mechanisms of MI-773 in neuroblastoma are still unclear. In this study, we used microarrays to analyze the global change in gene expression as a result of MI-773 treatment in the human neuroblastoma cell line SH-SY5Y.
Project description:The prognosis of the patients with neuroblastoma largely depends on the biological characterisitics. Neuroblastoma tissues obtained before any treatments were analyzed for gene expression using Affymetrix array. We used microarrays to detail the global programme of gene expression distinguishing tumor biology of neuroblastoma tisses from the prognosis of the patients.