Mouse models of sarcomas: critical tools in our understanding of the pathobiology

Sarcomas are a rare form of cancer with less than 15,000 new cases diagnosed each year in the United States. Though rare, sarcomas are highly debilitating malignancies as they are often associated with significant morbidity and mortality. Sarcomas are biologically very heterogeneous as evidenced by the fact that these cancers arise from a plethora of different tissues and cell types. They are classically defined by their tissue of origin and are additionally stratified by their histopathology or patient’s age at diagnosis [1,2]. While these classifications have proven useful, modern biological and clinical techniques have the ability to further stratify sarcomas based on their genetic profile [1,3,4]. Cytogenetic and karyotype analyses have revealed two divergent genetic profiles in sarcomas. The first and most simple genetic profile is the observation of translocation events in sarcomas with an otherwise normal diploid karyotype. On the other hand, most sarcomas display a more complex genetic phenotype, suggesting genomic instability plays an important role in many sarcomas.Much of our current knowledge regarding sarcoma biology has been ascertained through experimentation using high dose irradiation, viral infections, in vitro cell line studies, and xenografts models. One of the earliest animal studies investigated the impact of the Rous sarcoma virus on the development of soft tissue sarcomas [5]. Our knowledge regarding radiation-induced sarcomagenesis largely stems from the observation of women occupationally exposed to radium and animal models subjected to high dose radiation developed sarcomas [6,7]. While the plight of these patients and the subsequent animal experiments led to the identification of a cause and effect for some sarcomas, these observations were unable to identify the molecular events responsible for sarcomagenesis.To more accurately investigate the genetic and molecular changes manifested in sarcomas, scientists began using patient derived sa