p53 mutation and MDM2 amplification frequency in pediatric rhabdomyosarcoma tumors and cell lines

Background. The p53 tumor suppressor gene is the most commonly mutated gene in human cancer, and mutations arise in a wide variety of tumor types. Wil d-type p53 functions as a regulator of apoptosis, so mutations in the p53 g ene are generally associated with aggressive tumors and a poor prognosis. P rocedure. We have investigated the p53 mutation and MDM2 amplification freq uencies in biopsies from pediatric rhabdomyosarcoma (RMS) tumors and cell l ines by SSCP and Southern analyses. Results. A mutation was detected in onl y 1 of 20 tumor specimens (5%), whereas the frequency in established RMS ce ll lines was significantly higher (6/10, 60%). p53 Mutations were more comm on in cell lines derived from tumors previously exposed to chemotherapy com pared to those derived from tumors at diagnosis, and it is likely that thes e mutations enhanced the probability of successful long-term culture. The f requency of MDM2 gene amplification in patient biopsies was also low (2/20, 10%), interestingly, complete responses to treatment were obtained in the two patients with tumors that demonstrated amplification of MDM2. The respo nse to treatment of patients with tumors wild-type for p53 and without MDM2 amplification was quite varied, indicating that expression of a wild-type p53 gene at diagnosis cannot always facilitate a favorable outcome. Conclus ions. p53 mutation and MDM2 gene amplification frequencies are extremely lo w in RMS tumors, but a wild-type p53 genotype is not always associated with a Favorable prognosis. Med. Pediatr. Oncol. 35:96-103, 2000. (C) 2000 Wile y-Liss, Inc.