By comparison, the metastasis showed only minor differences regarding mutations and fusion transcripts, but had undergone WGD (Fig. 5d, Supplementary Figure 2c, and Supplementary Data 1), implying that tetraploidization was a progression event preceded by loss of wild-type TP53 and RB1. These data again indicated that LMS is driven by a perturbed tumor suppressor network (Fig. 5e), which gives rise to WGD and gross genomic instability, thereby accelerating tumor evolution, in the majority of cases19–21. Here, RB1 is linked to neoplasm.