Patients with the rare cancer predisposition Li-Fraumeni syndrome (LFS), carrying germline heterozygous TP53 PVs, appear to exhibit normal development yet are at an almost 100% lifetime risk to develop a wide spectrum of cancers [19, 20], predominantly sarcomas, adrenocortical carcinomas, brain tumors, breast cancer and leukemias [21], with a greater than 83-fold increased risk to develop multiple primary malignancies [22]. This evidence concerns the gene TP53 and Li-Fraumeni syndrome.