Osteosarcoma is the most common type of bone cancer. Osteosarcoma is commonly associated with TP53 inactivation (around 95% of cases) and RB1 inactivation (around 28% of cases). With the discovery of reprogramming factors to induce pluripotency even in terminally differentiated cells, induced pluripotent stem cells (iPSCs) have emerged as a promising disease model. iPSC-based disease modeling uniquely recapitulates disease phenotypes and can support discoveries into disease etiology and is used extensively today to study a variety of diseases, including cancers. This paper focuses on iPSC-based modeling of Li-Fraumeni syndrome (LFS), an autosomal dominant disorder commonly associated with TP53 mutation and high osteosarcoma incidence. As iPSCs are increasingly utilized as a platform for cancer modeling, the experimental approaches that we discuss here may serve as a guide for future studies.

骨肉瘤是最常见的骨癌类型。骨肉瘤通常与TP53失活（约 95% 的病例）和RB1失活（约 28% 的病例）相关。随着甚至在终末分化细胞中诱导多能性的重编程因子的发现，诱导多能干细胞（iPSC）已成为一种有前途的疾病模型。基于 iPSC 的疾病模型独特地概括了疾病表型，可以支持疾病病因学的发现，目前已广泛用于研究包括癌症在内的多种疾病。本文重点研究基于 iPSC 的 Li-Fraumeni 综合征 (LFS) 建模，LFS 是一种常染色体显性遗传疾病，通常与TP53突变和高骨肉瘤发病率相关。随着 iPSC 越来越多地用作癌症建模平台，我们在此讨论的实验方法可以作为未来研究的指南。