Abstract B71: A Systems Biology Approach to Study Ewing's Sarcoma

Ewing9s sarcoma is the second most frequent pediatric bone tumor. It is characterized in 85% of cases by a chromosomal translocation which leads to the expression of a chimeric transcription factor: EWS‐FLI1. This oncogene is transforming in various cell and animal models. Although important EWS‐FLI1 transcription targets and altered pathways have been described, a comprehensive understanding of the disease remains to be achieved. For this purpose, a systems biology approach was used. In this project, gene profiling of (1) primary tumors and (2) of EWS‐FLI1‐inducible cell models were performed. Based on these experimental data and on literature knowledge, we constructed an annotated influence network of EWS‐FLI1 effects that was validated using small scale silencing/qPCR experiments and home‐made software. In a second step, in order to better understand the global impact of EWS‐FLI1 in Ewing sarcoma context, EWS‐FLI1 ChIP‐seq experiments were performed. These results were combined to the gene expression profile data using rational approaches and/or PCA based analyses. This resulted in a genome wide analysis in which the genes were ranked upon their implication/significance in Ewing sarcoma. In the future, we intend to integrate these results to an extended version of our annotated influence network and confront high‐throughput experimental results (siRNA screen) with predictive computational models of this network. This should allow identifying novel crucial genes/pathways in Ewing9s sarcoma. Citation Information: Cancer Res 2009;69(23 Suppl):B71.