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Modeling the initiation of Ewing sarcoma tumorigenesis in differentiating human embryonic stem cells.

Oncogene | 2016

Oncogenic transformation in Ewing sarcoma tumors is driven by the fusion oncogene EWS-FLI1. However, despite the well-established role of EWS-FLI1 in tumor initiation, the development of models of Ewing sarcoma in human cells with defined genetic elements has been challenging. Here, we report a novel approach to model the initiation of Ewing sarcoma tumorigenesis that exploits the developmental and pluripotent potential of human embryonic stem cells. The inducible expression of EWS-FLI1 in embryoid bodies, or collections of differentiating stem cells, generates cells with properties of Ewing sarcoma tumors, including characteristics of transformation. These cell lines exhibit anchorage-independent growth, a lack of contact inhibition and a strong Ewing sarcoma gene expression signature. Furthermore, these cells also demonstrate a requirement for the persistent expression of EWS-FLI1 for cell survival and growth, which is a hallmark of Ewing sarcoma tumors.

Pubmed ID: 26455317 RIS Download

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Associated grants

  • Agency: Howard Hughes Medical Institute, United States
  • Agency: NCI NIH HHS, United States
    Id: K08 CA160346
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM083299

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Enrichr (tool)

RRID:SCR_001575

A web-based gene list enrichment analysis tool that provides various types of visualization summaries of collective functions of gene lists. It includes new gene-set libraries, an alternative approach to rank enriched terms, and various interactive visualization approaches to display enrichment results using the JavaScript library, Data Driven Documents (D3). The software can also be embedded into any tool that performs gene list analysis. System-wide profiling of genes and proteins in mammalian cells produce lists of differentially expressed genes / proteins that need to be further analyzed for their collective functions in order to extract new knowledge. Once unbiased lists of genes or proteins are generated from such experiments, these lists are used as input for computing enrichment with existing lists created from prior knowledge organized into gene-set libraries.

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Gene Set Enrichment Analysis (tool)

RRID:SCR_003199

Software package for interpreting gene expression data. Used for interpretation of a large-scale experiment by identifying pathways and processes.

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GenePattern (tool)

RRID:SCR_003201

A powerful genomic analysis platform that provides access to hundreds of tools for gene expression analysis, proteomics, SNP analysis, flow cytometry, RNA-seq analysis, and common data processing tasks. A web-based interface provides easy access to these tools and allows the creation of multi-step analysis pipelines that enable reproducible in silico research.

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