ASPSCR1TFE3

ASPSCR1-TFE3 is a recurrent fusion gene generated by a chromosomal translocation that fuses the ASPSCR1 gene (also known as ASPL) on chromosome 17 with the TFE3 gene on the X chromosome. In alveolar soft part sarcoma (ASPS), the translocation is t(X;17)(p11;q25). The resulting ASPSCR1-TFE3 transcript encodes a chimeric transcription factor containing the TFE3 DNA-binding domain, which localizes to the nucleus and drives aberrant expression of target genes. This deregulated transcription is a leading driver of tumor development in ASPS.

Detection and diagnosis rely on molecular methods: fluorescence in situ hybridization (FISH) or RT-PCR across the fusion breakpoint, and RNA sequencing can confirm the fusion. Immunohistochemistry may show strong nuclear TFE3 staining, supporting the presence of a TFE3 rearrangement.

Clinical significance: the fusion is a hallmark of alveolar soft part sarcoma and helps distinguish it from morphologically similar tumors. The ASPSCR1-TFE3 fusion informs prognosis and can guide therapeutic decisions; while there is no approved therapy that directly targets the fusion, ASPS is often treated with local control plus systemic therapies including anti-angiogenic agents and tyrosine kinase inhibitors, reflecting the tumor’s highly vascular biology. Ongoing research seeks to develop therapies that more specifically disrupt TFE3-driven transcription or its downstream signaling.