Which of the following is the hallmark translocation associated with Ewing's sarcoma, and what is its functional consequence?

• A t(9;22) — BCR-ABL fusion causing constitutive tyrosine kinase activity
• B t(2;13) — PAX3-FOXO1 fusion driving rhabdomyosarcoma differentiation
• C t(12;16) — FUS-DDIT3 fusion causing liposarcomatous differentiation
• D t(11;22)(q24;q12) — EWSR1-FLI1 fusion creating an aberrant transcription factor ✓

Explanation

Ewing's sarcoma is characterised in ~85% of cases by t(11;22)(q24;q12), producing an EWSR1-FLI1 fusion gene. The resulting chimeric protein is an aberrant transcription factor that promotes tumour cell proliferation and inhibits differentiation. The remaining 15% have variant EWS translocations (e.g. EWS-ERG). This translocation is diagnostically important and detectable by FISH or RT-PCR. BCR-ABL typifies CML; PAX3-FOXO1 is in alveolar rhabdomyosarcoma; FUS-DDIT3 is in myxoid liposarcoma.

Reference: Maheshwari Essential Orthopaedics, 6th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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