FUSDDIT3

FUS-DDIT3, also known as FUS-CHOP, is a fusion gene produced by the chromosomal translocation t(12;16)(q13;p11). The translocation fuses the N-terminal portion of FUS, an RNA-binding protein, to the C-terminal portion of DDIT3 (also called CHOP), yielding a chimeric transcription factor that drives oncogenesis in a subset of soft tissue sarcomas, most notably myxoid liposarcoma.

FUS-DDIT3 is considered the defining molecular abnormality of many myxoid liposarcomas, present in the majority of cases. The fusion protein acts as an abnormal transcription factor, altering expression of genes involved in adipocytic differentiation and cell proliferation, contributing to tumor development.

Detection methods include RT-PCR or fluorescence in situ hybridization (FISH) to identify the FUS-DDIT3 fusion, as well as sequencing-based approaches. The fusion is a key diagnostic marker used to distinguish myxoid liposarcoma from other sarcoma subtypes.

Most tumors arise in the soft tissues of the extremities or trunk; treatment typically involves surgical excision with radiotherapy, and chemotherapy may be used for advanced disease. The presence of the FUS-DDIT3 fusion helps confirm diagnosis and may inform prognosis and follow-up, but management is guided by tumor size, location, and metastasis.

Research investigates the molecular mechanisms by which FUS-DDIT3 reprograms transcription and adipogenesis, as well as potential targeted therapies that disrupt fusion activity or its downstream pathways.