Given the clinical evidence that some UESL arise from MHL, and that both UESL and MHL share C19MC structural variations, we hypothesize a multistep model for UESL genomic development: C19MC translocation could be the first event leading to a benign tumor, and in some cases TP53 mutation/loss occurs to lead malignant transformation to UESL (S2 Fig). Here, TP53 is linked to liver mesenchymal hamartoma.