FUS/EWSR1::TFCP2-rearranged Bone and Soft Tissue Tumors: Evidence of Gene Promiscuity.

The FET(FUS/EWSR1)::TFCP2 fusion defines a distinct molecular subtype of spindle cell/sclerosing rhabdomyosarcoma (RMS), typically involving the mandible and maxilla. These tumors demonstrate myogenic differentiation and are clinically aggressive. In addition to the characteristic fusion, they often show features of homologous recombination deficiency (HRD), genomic instability, and expression of ALK and TERT truncated variants. This study presents a cohort of 25 patients with FET::TFCP2 fusion, representing the largest single-center series to date. While most tumors involve bones, 8 cases are soft tissue tumors, including the cheek (2 cases), epididymis, bladder, abdominal wall, neck, temporal part, and scalp. Genomically, approximately 40