The Ewing's Sarcoma Oncoprotein EWS/FLI Induces a p53-Dependent Growth Arrest in Primary Human Fibroblasts

Cancer Cell 1, 393-401. Published: 2002.04.30

Stephen L. Lessnick, Caroline S. Dacwag, and Todd R. Golub

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Abstract

Ewing's sarcoma is associated with a fusion between the EWS and FLI1 genes, forming an EWS/FLI fusion protein. We developed a system for the identification of cooperative mutations in this tumor through expression of EWS/FLI in primary human fibroblasts. Gene expression profiling demonstrated that this system recapitulates many features of Ewing's sarcoma. EWS/FLI-expressing cells underwent growth arrest, suggesting that growth arrest-abrogating collaborative mutations may be required for tumorigenesis. Expression profiling identified transcriptional upregulation of p53, and the growth arrest was rescued by inhibition of p53. These data support a role for p53 as a tumor suppressor in Ewing's sarcoma, and demonstrate the use of transcriptional profiling of model systems in the identification of cooperating mutations in human cancer.

Keywords: Ewing's sarcoma microarray p53 pediatric cancer transcriptional profiling

Ewings rs

Supplemental Data

Description Link/Filename
Manuscript (PDF) CCELL.1_4_393.56.pdf
Appendix 1: Overview of appendices and methods (MS Word) Appendix 1.doc
Appendix 1: Overview of appendices and methods (PDF) Appendix 1.pdf
Appendix 2: Expression data from the tet-EF cell expt (Excel) Appendix_2.xls
Appendix 3: cls file for tet-EF cell knn analysis from fig. 2 Appendix_3.cls
Appendix 4a: cls file for Ewing's sarcoma Appendix_4a.cls
Appendix 4b: cls file for Burkitt's lymphoma Appendix_4b.cls
Appendix 4c: cls file for neuroblastoma Appendix_4c.cls
Appendix 4d: cls file for rhabdomyosarcoma Appendix_4d.cls
Appendix 5: limited tet-EF dataset (Excel) from fig. 2 Appendix_5.xls
Appendix 6: Limited SRCT dataset (Excel) from fig. 2 Appendix_6.xls
Appendix 7a: Ewing's-specific genes (Excel) Appendix_7a.xls
Appendix 7b: Burkitt's-specific genes (Excel) Appendix_7b.xls
Appendix 7c: neuroblastoma-specific genes (Excel) Appendix_7c.xls
Appendix 7d: rhabdomyosarcoma-specific genes (Excel) Appendix_7d.xls
Appendix 8: tet-EF cell upregulated genes (Excel) Appendix_8.xls
Appendix 9: SOM clusters from tet-EF cells (Excel) Appendix_9.xls
CEL files 1/2 (zip file, 15 MB) run1.tar.gz
CEL files 2/2 (zip file, 14 MB) run2.tar.gz
Sample descriptions for CEL files run_samples.txt