Status of topoisomerases in pediatric high grade osteosarcomas and their therapeutic and prognostic role

10030 Background: High grade osteosarcomas are the most common malignant bone tumors at adolescence. In the French group, they were treated until 2005 with OS94 guidelines, using a first line therapy of combined high dose-methotrexate and VP16- ifosfamide courses. In the poor response to these drugs, a second line therapy was administered associating doxorubicin and cisplatine. Both therapeutic strategies were based on topisomerase IIα inhibitor. Therefore, a retrospective and prospective molecular study of topoisomerase genes (TOP2A, TOP2B and TOP1) was conducted on diagnostic tumors consecutively collected from this population to understand their therapeutic and prognostic role. Methods: 91 patients were included. Paired normal and tumor biopsy tissues were analyzed by allelotyping, using microsatellites flanking on both sides each locus containing TOP1, TOP2A and TOP2B, coding for topoisomerase genes. These loci are respectively 20q12, 17q21 and 3p24. In addition to these genomic data, quantitative rea...