|Publication Type||Journal Article|
|Year of Publication||2002|
|Authors||Lessnick, SL, Dacwag, CS, Golub, TR|
|Pages||393 - 401|
|Keywords||Anti-Bacterial Agents, Bone Neoplasms, Cancer, Cell Division, Cell Survival, Cell Transformation, Cells, Cultured, DNA Primers, Fibroblasts, Gene Expression Profiling, Humans, Infant, Mutation, Neoplastic, Newborn, Oligonucleotide Array Sequence Analysis, Oncogen|
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.