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The molecular events leading to the development of pediatric bone tumors are not clear to date, but abnormal cell cycle progression has been reported in a wide variety of human tumors due to the alteration of several tumor suppressor genes. We have analyzed 55 bone sarcoma samples from pediatric patients to test the possibility that they harbor mutations in the p21WAF1 tumor suppressor gene. Mutation analysis was performed through denaturing gradient gel electrophoresis analysis of exon 2 of the gene and consequent cycle sequencing of the altered fragments. No mutations affecting the coding regions of the p21WAF1 were found. Nevertheless, we found genetic polymorphisms in nine of the samples analyzed. We conclude that p21WAF1 mutations do not play an important role in the development of this kind of pediatric malignancy.