a molecular function map of ewings sarcoma一个分子功能尤文氏肉瘤的地图.pdfVIP

A Molecular Function Map of Ewing’s Sarcoma 1. 1. 2 3 3 3 Maximilian Kauer , Jozef Ban , Reinhard Kofler , Bob Walker , Sean Davis , Paul Meltzer , Heinrich Kovar1* 1 Children’s Cancer Research Institute, St. Anna Kinderkrebsforschung, Vienna, Austria, 2 Biocenter, Division of Molecular Pathophysiology, Medical University Innsbruck, Innsbruck, Austria, 3 Genetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America Abstract Background: EWS-FLI1 is a chimeric ETS transcription factor that is, due to a chromosomal rearrangement, specifically expressed in Ewing’s sarcoma family tumors (ESFT) and is thought to initiate the development of the disease. Previous genomic profiling experiments have identified EWS-FLI1–regulated genes and genes that discriminate ESFT from other sarcomas, but so far a comprehensive analysis of EWS-FLI1–dependent molecular functions characterizing this aggressive cancer is lacking. Methodology/Principal Findings: In this study, a molecular function map of ESFT was constructed based on an integrative analysis of gene expression profiling experiments following EWS-FLI1 knockdown in a panel of five ESFT cell lines, and on gene expression data from the same platform of 59 primary ESFT. Out of 80 normal tissues tested, mesenchymal progenitor cells (MPC) were found to fit the hypothesis that EWS-FLI1 is the driving transcriptional force in ESFT best and were therefore used as the reference tissue for the construction of the molecular function map. The interrelations of molecular pathways were visualized by measuring the similarity among annotated gene functions by gene sharing. The molecular