EWSR1ERG

EWSR1ERG, also written EWSR1-ERG, is a gene fusion arising from chromosomal translocation between the EWSR1 gene on chromosome 22 and the ERG gene on chromosome 21. It is one of several EWSR1 fusion variants observed in Ewing sarcoma family tumors (ESFT) and is less common than the canonical EWSR1-FLI1 fusion.

Molecularly, the fusion typically combines the N-terminal transactivation domain of EWSR1 with the ETS DNA-binding domain of ERG, producing an abnormal transcription factor that drives oncogenic gene expression. This altered transcriptional activity contributes to the tumorigenic program seen in affected cells.

Clinically, EWSR1-ERG–positive tumors most often present as bone or soft tissue masses in children and young adults. Histologically they resemble other ESFTs, typically exhibiting small round blue cell morphology. Immunohistochemistry often shows CD99 membranous positivity and may include NKX2-2 expression. Definitive diagnosis requires molecular confirmation, commonly via FISH showing EWSR1 rearrangement and either RT-PCR or RNA sequencing identifying the EWSR1-ERG fusion. Distinguishing EWSR1-ERG from EWSR1-FLI1 is important for diagnostic accuracy and research context, though treatment approaches largely align with other ESFTs.

Treatment and prognosis follow standards for Ewing sarcoma family tumors, including multi-agent chemotherapy with local control measures such as surgery and/or radiotherapy. Prognosis depends on disease stage and response to therapy; localized disease generally has a more favorable outcome than metastatic disease, and outcomes vary across patient cohorts.