## Chromosomal Abnormality in Ewing Sarcoma **Key Point:** The translocation t(11;22)(q24;q12) is found in ~90% of Ewing sarcomas and is considered pathognomonic for this tumor. ### Molecular Mechanism This translocation results in fusion of the **EWS gene** (chromosome 22) with the **FLI1 gene** (chromosome 11), creating the **EWS-FLI1 fusion protein**. This aberrant protein acts as an oncogenic transcription factor, driving uncontrolled cell proliferation and tumor development. ### Diagnostic Significance - Present in the vast majority of classic Ewing sarcomas - Can be detected by **FISH** (fluorescence in situ hybridization) or **RT-PCR** - Helps distinguish Ewing sarcoma from other small round cell tumors of bone - Variants exist (e.g., EWS-ERG fusion in ~5–10% of cases), but t(11;22) remains the gold standard **High-Yield:** The EWS-FLI1 fusion is not only diagnostic but also prognostic—it defines the molecular subtype of the tumor and may guide targeted therapy in the future. **Clinical Pearl:** Absence of this translocation does not rule out Ewing sarcoma, as rare variants exist, but its presence is highly specific. 
Sign up free to access AI-powered MCQ practice with detailed explanations and adaptive learning.