GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE285nnn/GSE285855/suppl/filelist.txtftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE285nnn/GSE285855/suppl/GSE285855_RAW.tarftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE285nnn/GSE285855/primaryOK200GenomicsHomo sapiensGenome binding/occupancy profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE285855GEOGSEfalseFusion-positive rhabdomyosarcoma oncofusions share a common interactomeThe sole reoccurring oncogenic mutation in the pediatric cancer of fusion-positive rhabdomyosarcoma is a reciprocal translocation giving rise to a transcriptional oncofusion comprised of the N-terminus of the PAX3 transcription factor encoding DNA-binding domains fused in-frame to the C-terminus of the FOXO1 transcription factor encoding a transactivation domain. However, a host of new translocations have been detected in this cancer that are known or predicted to encode a protein comprised of the same PAX3 or its paralog PAX7 N-terminus, but with very different C-terminal fusion partners. How such different oncofusions cause the identical cancer was unknown. Here we show that these oncofusions are functionally interchangeable and engage a common interactome of proteins and activate a core shared transcriptional program. Interestingly, this common interactome contains the C-terminal fusion partners or their paralogs of all tested oncofusions, as well as the C-terminal fusion partner of a novel oncofusion. We thus suggest that oncofusions originate in rhabdomyosarcoma from the same DNA-binding domain fused to proteins within a common interactome, which in turn engages a core set of genes giving rise to this cancer.2026/04/09GSE285855GSM8710394GSM8710393GSM8710396GSM8710395GSM8710398GSM8710397GSM8710400GSM8710399GSM8710402GSM871040130882285855Homo sapiens