Abstract

Significance We present, to our knowledge, the first comprehensive next-generation sequencing of osteosarcoma in combination with a functional genomic screen in a genetically defined mouse model of osteosarcoma. Our data provide a strong rationale for targeting the phosphatidylinositol 3-kinase/mammalian target of rapamycin pathway in osteosarcoma and a foundation for rational clinical trial design. These findings present an immediate clinical opportunity because multiple inhibitors of this pathway are currently in clinical trials.