RB1 and osteosarcoma: Like RB1 dysfunction, TP53 serves as a cell-cycle checkpoint regulator and inherited loss of function mutations displays Mendelian inheritance characteristics in an autosomal dominant fashion.124 Heterozygous germline variation in the TP53 allele results in a lifetime cancer risk of ≥90% for women and ≥70% for men.130 The five most common malignancies in these patients are adrenocortical carcinomas, breast cancer, central nervous system tumors, osteosarcomas, and soft-tissue sarcomas.131