Low expression of p63 and p73 in osteosarcoma. The recent discovery of two p53-related genes, p63 and p73, has revealed an additional level of complexity to the study of p53 function. Both genes encode multiple proteins arising from alternative promoter usage and splicing, with transactivation, DNA-binding, and tetramerization domains. Recent data support a role for p63 in squamous and transitional cell carcinomas, as well as in certain lymphomas and thymomas.To characterize the involvement of p63 and p73 in the development of osteosarcoma, we analyzed the expression and mutation of TAp63 and TAp73 in six osteosarcoma cell lines and twelve osteosarcoma specimens.Semiquantitative DNA/PCR analysis revealed that eight (67%) and six (50%) out of twelve osteosarcoma specimens showed significantly reduced levels of p63 and p73 transcription, respectively. Direct sequencing of the entire coding region detected no mutations in cell lines or osteosarcoma specimens.Our data suggest that low expression of p63 and p73 is relatively common in osteosarcomas and might contribute to their molecular pathogenesis.