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
Read ManuscriptAbstract
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
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 |