BACKGROUND: Somatic and constitutional mutation screening of p53 in childhood sarcomas and retinoblastoma was investigated by a multitechnical approach to evaluate its role in the development/progression by somatic mutation events and/or genetic predisposition. MATERIAL/METHODS: The studies were carried out on a cohort of 100 sarcoma cases, i.e. Ewing's sarcoma (n=44), osteosarcoma (n=36), and rhabdomyosarcoma (n= 20), and on 50 retinoblastoma (Rb) cases. RESULTS: Constitutional allelic deletion was found by FISH in 4% of sarcoma cases. Overall, 20% of sarcoma tumors showed p53 rearrangement by PCR/SSCP and Southern blot. Allelic deletion of p53 was detected in 78% of sarcoma and 55% of Rb tumors. p53 protein expression was detected by immunohistochemistry in 20% of sarcoma tumors. CONCLUSIONS: This study for the first time provided evidence of p53 alteration through allelic deletion that are common primary somatic mutation events which occur irrespective of grade and stage and are hence probably associated with an early phase of tumorigenesis and/or tumor progression. The studies also explored the occurrence of de novo constitutional deletion of p53 in sporadic childhood sarcomas. This study in retinoblastoma provided evidence for the synergistic role of RB1 and p53, probably essential for the full-blown development of malignancy.

Keywords: In Situ Hybridization, Fluorescence, Sarcoma, Ewing - genetics, Sarcoma - genetics, Rhabdomyosarcoma - genetics, Retinoblastoma - genetics, Retinal Neoplasms - genetics, Polymorphism, Single-Stranded Conformational, Polymerase Chain Reaction, Point Mutation, Osteosarcoma - genetics, Infant, Newborn, Adolescent, Germ-Line Mutation, Genes, p53, Gene Dosage, Gene Deletion, DNA Primers - genetics, Child, Preschool, Child, Bone Neoplasms - genetics, Base Sequence