Fig. 2
PAX3-FOXO1 fusion gene in rhabdomyosarcoma (RMS). RMS rare type of cancer that can be highly aggressive. It starts as a growth of cells in the soft tissue. There are several types of RMS, including embryonal (eRMS) and alveolar (aRMS), with aRMS being the far more aggressive. The PAX3-FOXO1 fusion gene is a signature genetic alteration for aRMS. It consists of a stable reciprocal translocation of chromosomes 2 and 13, t(2;13), which generates two derivative chromosomes, der(2) and der(13) (top left panel). The der(2) chromosome contains the FOXO1-PAK3 fusion gene, which encodes a protein lacking major functional domains, and the der(13) chromosome contains the PAX3-FOXO1 fusion gene, which encodes the PAX3-FOXO1 fusion transcription factor with enhanced transcriptional activity (top right panel). The PAX3 gene encodes a member of the PAX family of transcription factors. FOXO1 is also a transcription factor. In the PAX3-FOXO1 fusion, the in-frame DNA binding domain of PAX3 is fused with the transactivation domain of FOXO1, generating a transcription factor with powerful transcriptional power, altered post-translational regulation, and possibly new targets.88 As a pioneer factor, PAX3-FOXO1 alters the local chromatin structure and binding to repressed, inaccessible chromatin, and transcriptional activation (bottom panel). PAX3 paired box 3, FOXO1 forkhead box O1
