Various mechanisms of YAP1 activation have been described in mesenchymal tumors, including (i) (epi-)genetic deregulation of Hippo pathway tumor suppressors [27]; (ii) Hippo pathway inhibition, as reported in alveolar rhabdomyosarcoma in which the PAX3-FOXO1 fusion-mediated upregulation of RASSF4 inhibits MST1 [28]; and (iii) involvement of YAP1 in chromosomal translocations in epithelioid hemangioendothelioma (YAP1-TFE3) and sclerosing epithelioid fibrosarcoma (YAP1-KMT2A) [29, 30]. This evidence concerns the gene TFE3 and alveolar rhabdomyosarcoma.