Osteosarcoma.

It has been difficult to identify the molecular features central to the pathogenesis of osteosarcoma owing to a lack of understanding of the cell or origin, the absence of identifiable precursor lesions, and its marked genetic complexity at the time of presentation. Interestingly, several human genetic disorders and familial cancer syndromes, such as Li-Fraumeni syndrome, are linked to an increased risk of osteosarcoma. Association of these same genetic alterations and osteosarcoma risk have been confirmed in murine models. Osteosarcoma is associated with a variety of genetic abnormalities that are among the most commonly observed in human cancer; it remains unclear, however, what events initiate and are necessary to form osteosarcoma. The availability of new resources for studying osteosarcoma and newer research methodologies offer an opportunity and promise to answer these currently unanswered questions. Even in the absence of a more fundamental understanding of osteosarcoma, association studies and preclinical drug testing may yield clinically relevant information.