RB1 and Li-Fraumeni syndrome: While it has been known that patients with Li-Fraumeni syndrome or hereditary retinoblastoma, which are associated with germline defects in TP53 and RB1, respectively, have an increased risk for developing LMS as secondary malignancy45, 46, the frequency of TP53 and RB1 disruption in sporadic LMS was reported to be in the range of 50% or lower3, 43, 44.