Ewing sarcoma breakpoint region 1–Friend leukemia virus integration 1 fusion mRNA (EWS-FLI1 fusion mRNA)

The Ewing sarcoma breakpoint region 1–Friend leukemia virus integration 1 (EWS-FLI1) fusion mRNA is the chimeric transcript generated by a t(11;22)(q24;q12) chromosomal translocation that fuses the EWSR1 gene (chromosome 22) with the FLI1 gene (chromosome 11); this mRNA encodes the EWS-FLI1 fusion protein, a potent oncogenic transcription factor and the primary molecular driver of Ewing sarcoma[1][3][6]. The EWS-FLI1 fusion protein hijacks regulatory networks in affected cells, dramatically altering gene expression through both transcriptional activation and repression, as well as influencing chromatin remodeling and alternative splicing[1][2][5]. The fusion protein is considered *pathognomonic* for Ewing sarcoma, being present in about 90% of tumors, and its detection at the mRNA level serves as a highly specific diagnostic marker[1][6]. EWS-FLI1 drives proliferation, inhibits differentiation, and maintains the malignant phenotype of tumor cells. Targeting EWS-FLI1 mRNA or protein is an area of active therapeutic investigation, with small molecules such as YK-4-279 and TK216 disrupting fusion-specific interactions and thus attenuating its oncogenic functions[5]. Therapeutic targeting is complicated by specificity and delivery concerns, but EWS-FLI1 remains a central focus for drug discovery and molecular diagnostics in Ewing sarcoma[1][4][5][6].

Other names

EWS/FLI1 fusion mRNAEWS-FLI1 (protein or mRNA contexts)EWS::FLI1EWSR1-FLI1 fusionEWS-FLI-1

Disruption of protein–protein interactions (e.g., between EWS-FLI1 and RHA/DDX5); Inhibition of EWS-FLI1 transcriptional and oncogenic activities