Amplification of the MYC Gene in Osteosarcoma Secondary to Paget's Disease of Bone

Purpose. In a previous series of 25 human osteosarcoma samples studied for MYC gene amplification, we found amplification in two cases (8%), including one arising in association with Paget's disease (pagetic osteosarcoma). Based on this observation, we further investigated the prevalence of MYC gene amplification in pagetic osteosarcomas. Methods. MYC gene amplification was assessed by Southern blot analysis using frozen tissue samples in five cases of pagetic osteosarcoma and 53 cases of primary (non-pagetic) osteosarcoma. Amplification was considered present if the MYC copy number was six or greater. Results. Three out of five patients (60%) with pagetic osteosarcoma showed MYC gene amplification, whereas it was present in only 5/53 patients (9.4%) with primary osteosarcoma. The incidence of MYC amplification in pagetic osteosarcoma was thus significantly higher than that in primary osteosarcoma (p = 0.016). Discussion. The finding that MYC gene amplification may be more common in pagetic than primary osteosarcoma warrants further study and suggests pathogenetic differences between primary osteosarcomas and those arising in the setting of Paget's disease. Three of the four pagetic osteosarcomas from the present study were previously shown to be immunoreactive for p53, suggesting that p53 mutation may also be a frequent genetic lesion in these tumors.