Affiliation:
1. Department of Orthopaedic Surgery and Center for Children's Cancer Research, Huntsman Cancer Institute, The University of Utah, Salt Lake City, UT 84112, USA
Abstract
Osteosarcoma remains a deadly malignancy afflicting adolescents and young adults. The lack of a precursor and the panoply of genetic aberrations present in identified osteosarcomas makes study of its initiation difficult. A number of candidate hypotheses have been tested in the mouse, a species with a higher background incidence of osteosarcoma. Chemical carcinogens, external beam radiation, and bone-seeking heavy metal radioisotopes have all proven to be osteosarcomagenic in wild-type mice. A number of oncogenes, introduced via integrating viruses or aberrantly activated from heritable genetic loci, participate in and can individually drive osteosarcomagenesis. Germline and conditional gene ablations in the form of some but not all aneuploidy-inducing genes, conventional tumor suppressors, and factors that function normally in mesenchymal differentiation have also proven osteosarcomagenic, especially in combinations that silence theRb1andp53pathways. This paper reviews the rich history of mouse models of osteosarcomagenesis, what they have taught us about the human disease, and what future mouse experiments yet promise to teach.
Funder
National Institutes of Health
Subject
Radiology, Nuclear Medicine and imaging,Oncology
Cited by
36 articles.
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