PAX7FOXO1

PAX7-FOXO1 is a chromosomal translocation-derived fusion gene associated with a subset of alveolar rhabdomyosarcoma (ARMS). It results from the juxtaposition of the PAX7 gene on chromosome 1 with the FOXO1 gene on chromosome 13, producing a chimeric transcription factor that drives oncogenic programs in skeletal muscle lineage cells.

The PAX7-FOXO1 fusion protein combines the N-terminal DNA-binding domains of PAX7 with the C-terminal transactivation domain of FOXO1. This configuration alters normal transcriptional regulation, leading to abnormal expression of genes involved in myogenic differentiation, cell cycle control, and survival. The fusion protein acts as a potent aberrant transcription factor, contributing to the oncogenic process by promoting cell proliferation and blocking terminal differentiation.

Clinically, PAX7-FOXO1 is one of the principal fusion drivers in ARMS. It accounts for a substantial minority of ARMS cases, with PAX3-FOXO1 being the more common partner in this cancer type. The presence of a FOXO1 fusion gene, including PAX7-FOXO1, has diagnostic and prognostic implications and is used to classify tumors more precisely. Detection methods include reverse transcription polymerase chain reaction (RT-PCR), fluorescence in situ hybridization (FISH), and next-generation sequencing-based assays.

Prognostically, fusion status informs risk stratification in ARMS, though outcomes depend on multiple factors such as stage, tumor site, and treatment. Some studies suggest differences in prognosis between PAX7-FOXO1- and PAX3-FOXO1-positive tumors, but results are not absolute and continue to be evaluated in clinical trials and comparative analyses.

For further context, see also PAX3-FOXO1 and alveolar rhabdomyosarcoma.