Molecular pathology and molecular pharmacology of osteosarcoma

Abnormalities of many tumor suppressor genes and oncogenes have been descri bed in osteosarcoma, but separating early or primary from secondary or late genetic lesions has been difficult. Among early lesions, inactivation of b oth the P53 and RB pathways appears to be a central and perhaps necessary e vent in osteosarcomagenesis. We propose a working model for the molecular p athology of osteosarcoma and we review the numerous published studies exami ning the association of various molecular features with either advanced pre sentation, poor chemotherapy response or decreased patient survival.