GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE303nnn/GSE303259/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE303259GEOGSEfalseSRF fusion oncogenes encode constitutively activated chimeric transcription factors in myoid soft tissue tumors [C2C12]SRF fusion genes result from chromosomal translocations in muscle-related soft tissue tumors, including perivascular tumors, myofibroma and rhabdomyosarcoma. SRF encodes the Serum Response Factor, a well-characterized transcription factor that dimerizes and associates with the cofactors TCF or MRTF to regulate muscle development. Here, we characterized four SRF fusion genes: SRF::RELA, SRF::FOXO1, SRF::ICA1L and SRF::PDGFRB. All fusions proteins were nuclear and dimerized through the SRF MADS box. SRF::RELA, SRF::FOXO1, and SRF::ICA1L acted as constitutively active transcription factors, independently of canonical cofactors. Their activity depended on the DNA-binding MADS box of SRF and the transactivation domain of the partner protein. We identified a cryptic transactivation domain within cytosolic ICA1L. These three SRF fusions promoted mesenchymal cell proliferation and upregulated muscle-related genes. They are representative of 98% of the identified SRF fusion cases. In contrast, SRF::PDGFRB activity relied on the tyrosine kinase domain and was sensitive to imatinib. SRF::PDGFRB acted as an oncogene in Ba/F3 cells, activated STAT1 signaling, and induced an interferon-like inflammatory response, in line with the inflammatory myofibroblastic tumor, in which that fusion was identified. In conclusion, SRF fusions constitute a novel family of oncogenes supporting cell proliferation and expression of muscle differentiation markers in myoid soft tissue tumors.2026/07/18GSE303259GSM9122051GSM9122040GSM9122050GSM9122053GSM9122042GSM9122041GSM9122052GSM9122044GSM9122043GSM9122046GSM9122045GSM9122048GSM9122037GSM9122047GSM9122039GSM9122038GSM912204924247303259Mus musculus