MDM2 Gene Amplification in Metastatic Osteosarcoma1

The human homologue of the murine double minute 2 gene (MDM2), a p53-binding protein which may act as a regulator of p53 protein function, has recently heen cloned. Initial studies of this gene in a variety of human tumors have shown frequent gene amplification in most types of sarcomas, including osteosarcomas. Amplification of the MIÌM2 gene may produce a functional inactivation of the p53 protein. To examine possible clinical or pathological correlates of MI)\I2 gene amplification in osteosarcoma, we studied 28 specimens on 26 patients with high grade nsteosarcoma (16 primary, 11 metastatic, and 1 local recurrence) for MDM2 gene amplifi cation by Southern blot analysis, using two MDM2 complementary DNA probes isolated by polymerase chain reaction. Four specimens (14%) showed amplification, including 3 métastasesand 1 local recurrence. None of the primary osteosarcoma specimens had detectable MDM2 gene am plification. None of the specimens tested showed MDM2 gene rearrange ment. In the present series, MDM2 gene amplification was detected sig nificantly more frequently in metastatic or recurrent osteosarcomas than it was in primary osteosarcomas i /' = 0.02). Our data suggest that MDM2 gene amplification may be associated with tumor progression and metas tasis in osteosarcoma. Further investigation is warranted on the potential clinicopathological correlates of MDM2 gene amplification in osteosar coma.