Osteosarcomagenesis: Modeling Cancer Initiation in the Mouse

Figure 2

Genetically wild-type cells can naturally accrue sufficient mutations to initiate osteosarcomagenesis in mice as evidenced by the background incidence of osteosarcomas a little under 5 percent in most strains (A). Genetically induced aneuploidy alone, in most of its forms, is inefficient in osteosarcomagenesis (B). Expression of oncogenes as transgenes using native promoters, introduced via insertional viral vectors or unmasked by radiation, can lead to benign and malignant bone neoplasia in mice (C). Inherited germline deletion of tumor suppressors in heterozygosity or homozygosity or generation of mouse chimeras of cells with and without such deletions to avoid serious developmental defects have proven the efficiency of many gene inactivations in osteosarcomagenesis (D). Another means by which severe developmental phenotypes may be eschewed or potential cells of origin tested is by the use of conditional oncogene activation or conditional tumor suppressor ablation, specified either temporally or, by tissue, spatially (E); combinations of tumor suppressor deletions, possible in conditional ablation methods, have been very efficient at driving osteosarcomagenesis.