High-grade osteosarcoma is a malignant tumor of bone with diverse genomics, including mutations in TP53, RB1, FGFR1, IGF1R, and DNA structural alterations.4-7 In most sarcomas, including osteosarcoma, chemotherapy has traditionally been the backbone of therapy as there is an absence of classic kinase alterations as the main drivers (with exceptions such as GI stromal tumor [GIST], dermatofibrosarcoma protuberans, and inflammatory myofibroblastic tumor [IMT]). The gene discussed is RB1; the disease is osteosarcoma.