## Oncogene Activation by Translocation **Key Point:** MYC is the proto-oncogene most frequently activated by chromosomal translocation, particularly in hematologic malignancies. The classic example is t(8;14) in Burkitt lymphoma. ### MYC Translocation Patterns **High-Yield:** MYC activation by translocation occurs in: - **Burkitt lymphoma:** t(8;14)(q24;q32) — MYC juxtaposed to immunoglobulin heavy chain (IGH) locus - **Variant translocations:** t(2;8) and t(8;22) — MYC with kappa and lambda light chain loci - **Other B-cell lymphomas:** t(8;14) in diffuse large B-cell lymphoma (DLBCL) ### Mechanism of MYC Activation by Translocation 1. Translocation places MYC coding sequence adjacent to highly active immunoglobulin or T-cell receptor promoter 2. MYC transcription driven by constitutively active immunoglobulin/TCR enhancer 3. Overexpression of MYC protein (transcription factor) 4. Uncontrolled cell proliferation and apoptosis resistance ### Comparison of Activation Mechanisms | Oncogene | Primary Mechanism | Example | | --- | --- | --- | | MYC | Translocation | t(8;14) in Burkitt lymphoma | | RAS | Point mutation | Codon 12/13/61 mutations | | EGFR | Point mutation, amplification | Exon 19 deletions in lung cancer | | BCR-ABL | Translocation | t(9;22) in CML | | HER2 | Gene amplification | Breast cancer | **Clinical Pearl:** MYC translocations are hallmark lesions in Burkitt lymphoma and are used diagnostically via FISH (fluorescence in situ hybridization) and cytogenetics. **Mnemonic:** **MYC = Make Your Cell proliferate** — transcription factor driving uncontrolled growth when overexpressed via translocation. ### Why MYC is Most Common for Translocation - MYC is a transcription factor; overexpression alone drives transformation - Immunoglobulin and TCR loci are naturally active in lymphoid cells - Translocations are detectable and diagnostically significant - Occurs early in lymphomagenesis [cite:Robbins 10e Ch 7]
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