RB1 and retinoblastoma: Although genetic predisposition is only found in few osteosarcoma cases, investigations in syndromes like Li-Fraumeni (TP53), Retinoblastoma (RB1), and DNA helicase-related conditions Rothmund-Thomson (RECQL4) and Werner (RECQL2) have led to speculation and identification of some of the most important genes involved in osteosarcoma, like the RB1 gene mutations and TP53 germline mutations [80, 81].