MOLECULAR ALTERATIONS OF THE RB1, TP53, AND MDM2 GENES IN PRIMARY ANDXENOGRAFTED HUMAN OSTEOSARCOMAS

We report the status of the RB1, TP53, and MDM2 genes in human osteosa rcomas and cell lines established from surgical specimens and transpla nted into athymic naked mice. By using reverse transcriptase-polymeras e chain reaction (RT-FCR) as a prescreening technique and posterior se quencing, we observe new mutations in the RB1 gene, notably a duplicat ion in tan dem of exons 3 through 6. TP53 mutations appear in codons m ost frequently mutated in osteosarcomas. We have not seer MDM2 gene am plification in any reported case. These molecular alterations appear i n different osteosarcomas not simultaneously present in the same tumor sample. A link has been described between these three genes in the pa thways that control the cell cycle and the tumoral progression, but th eir functions are probably independent in the development of osteosarc omas. TP53 mutations appear in adult patients, whereas RB1 alterations occur mostly in younger patients.