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Abstract
Osteosarcoma is a primary malignant bone tumor that accounts for 5% of childhood cancers. Despite the use of chemotherapy, long-term survival has reached a plateau, and this figure has not changed for almost 20 years. Therefore, there is a need for understanding of the basic biology and pathogenesis of osteosarcoma in order to develop more therapeutic strategies and ultimately improve survival. This article reviews current state of knowledge about several aspects of osteosarcoma biology with regard to host genetic predispositions, cytogenetics and molecular markers. Genetic conditions with a predisposition to osteosarcoma include hereditary retinoblastoma, Li-Fraumeni syndrome, Rothmund-Thomson syndrome and Werner syndrome. Although most of osteosarcomas are sporadic, these syndromes may provide important clues to the pathogenesis of sporadic osteosarcomas. A multitude of cytogenetic abnormalities have been detected, but no specific abnormalities that can serve as markers of osteosarcoma have been found. Areas of molecular aberrations include tumor suppressor pathway (RB and p53), oncogenes (Her-2), telomere maintenance, angiogenesis (VEGF), chemokines (CXCR4), cytoskeletons (Ezrin), matrix metalloproteinases and adhesion molecules (CD44). Understanding the contributions of the different cytogenetic and molecular aberrations will aid in discovering predictors of outcome and in devising therapies for osteosarcoma.
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