While the extracellular domain of ADAM17 is involved in substrate recognition and cleavage, it is interesting that the mutations we detected in metastatic SS are located in the cytoplasmic domain of this protein because the cytoplasmic domain contains phosphorylation sites, including Thr735, Ser791 and Ser819, and interacts with intracellular signaling molecules [47]. The gene discussed is ADAM17; the disease is synovial sarcoma.