Forced expression of EWS-ATF1 induces soft tissue sarcomas

INTRODUCTION: Clear cell sarcoma (CCS), also called malignant melanoma of soft parts, is an aggressive malignant soft-tissue tumor that usually develops in the tendons and aponeuroses of the extremities of young adults (Enzinger, 1965). The origin and pathogenesis of this disease are poorly understood, and beneficial therapy—except for surgical resection—has not yet been developed. The high rates of local recurrence and metastasis result in a 5-year overall survival rate of less than 50%. The characteristic t(12;22)(q13;q12) chromosomal translocation seen in CCSs leads to a fusion gene that encodes the Ewing’s sarcoma (EWS)/activating transcription factor 1 (ATF1) fusion protein (Bridge et al., 1990). Previous studies have shown that EWS/ATF1 has oncogenic potential in CCS in vitro, but the effect of EWS/ATF1 on sarcoma formation in vivo is not yet known (Davis et al., 2006; Jishage et al., 2003). By analyzing EWS/ATF1 transgenic mice, we aim to determine whether EWS/ATF1 expression is sufficient for CCS induction.