Identification of potential chemoresistance genes in osteosarcoma. Osteosarcoma (OS) is an aggressive bone malignancy that primarily affects children and adolescents. Patients with metastatic disease at diagnosis have only a 20% survival rate. The poor survival rate of these patients is largely due to their lack of responsiveness to chemotherapy. However, the mechanisms underlying osteosarcoma chemoresistance remain unknown.The effect of cisplatin, doxorubicin and etoposide was examined on OS cell lines. Affymetric Genechip analysis was used to examine differential gene expression.A correlation between increasing metastatic potential and increasing chemoresistance was observed in the MG-63 cell line and sub-line model. Microarray analysis of these cell lines revealed the differential expression of several genes potentially involved in chemoresistance including ABCG2, ADD3, NMT2, WNTSa and PTN.The identification of genes contributing to chemoresistance and determining the role these genes play is critical in characterizing patient responsiveness and overcoming chemoresistance in osteosarcoma patients.