EWSR1FLI1Fusionsgen

The EWSR1-FLI1 fusion gene is a chimeric gene formed by a chromosomal translocation, most commonly t(11;22)(q24;q12), that fuses the EWSR1 gene on chromosome 22 to the FLI1 gene on chromosome 11. The resulting fusion produces an abnormal transcription factor that combines the transcriptional activation domain of EWSR1 with the DNA-binding domain of FLI1, altering gene expression patterns in cells.

This fusion is the hallmark molecular abnormality of the Ewing sarcoma family of tumors (ESFT), which includes Ewing sarcoma of bone and soft tissue. The EWSR1-FLI1 oncoprotein drives oncogenesis by misregulating a network of target genes involved in cell proliferation, survival, and differentiation. Multiple fusion variants exist, with Type 1 (EWSR1 exon 7 fused to FLI1 exon 6) and Type 2 among the most frequently observed, differing in the exact breakpoint but producing a functionally active fusion protein.

Diagnosis often relies on detecting the fusion gene or transcript rather than morphology alone. Detection methods include reverse transcription PCR (RT-PCR), fluorescence in situ hybridization (FISH), and next-generation sequencing (NGS) to identify EWSR1-FLI1 rearrangements. Immunohistochemistry for CD99 is frequently positive in ESFT but is not specific to Ewing sarcoma.

Clinically, the presence of EWSR1-FLI1 supports diagnosis and helps guide management. Treatment typically involves multimodal therapy, including multi-agent chemotherapy, local control through surgery or radiotherapy, and consideration of clinical trials. Prognosis depends on factors such as disease extent at presentation, tumor size, and response to chemotherapy; the fusion gene remains a key focus of ongoing research into targeted therapeutic strategies.