EWSR1Fusionsgene

EWSR1 fusion genes are recurrent chromosomal rearrangements that involve the EWSR1 gene on chromosome 22. The normal EWSR1 gene encodes an RNA-binding protein involved in transcription and RNA processing. In fusion events, the 5' portion of EWSR1 is joined to the 3' portion of a partner gene, creating a chimeric transcription factor with the potent transactivation domain of EWSR1 and the DNA-binding domain of the partner. This aberrant protein drives oncogenic gene expression.

The most well-known example is EWSR1-FLI1, the defining driver of most Ewing sarcoma cases. Other partners include ERG, ETV1, ETV4, and FEV, giving rise to additional Ewing-family fusion proteins such as EWSR1-ERG and EWSR1-ETV1/ETV4. EWSR1 can also fuse with ATF1 in clear cell sarcoma and related soft tissue tumors, and with WT1 in desmoplastic small round cell tumor. These fusions are important diagnostic hallmarks and contribute to tumor classification and biology.

Detection of EWSR1 fusions is achieved through fluorescence in situ hybridization (FISH), reverse transcription PCR, and next-generation sequencing methods such as RNA sequencing. Immunohistochemistry can support the diagnosis but is not specific for the fusion status. Identification of an EWSR1 fusion helps distinguish Ewing sarcoma and related neoplasms from morphologically similar tumors and guides clinical decision-making.

Clinically, the specific fusion type can carry prognostic information in some Ewing sarcoma cases, and research continues into therapies that target fusion-driven transcriptional programs. EWSR1 rearrangements are valuable diagnostic biomarkers and potential therapeutic targets across several sarcoma subtypes.