Based on our preclinical findings, indicating a major role of CREB in SySa tumorigenesis, these rare mesenchymal tumors appear to functionally join clear cell sarcoma, in which EWSR1-CREB or EWSR1-ATF1 gene fusions drive sarcomagenesis, directly involving CREB within the fusion protein [37, 38]. This evidence concerns the gene EWSR1 and clear cell sarcoma.