A research study examines telomerase activity in neoplasia. In normal somatic cells, telomerase is repressed, leading to telomere shortening with each division. In the context of carcinogenesis, which event most accurately describes the role of critically short telomeres BEFORE telomerase reactivation?
- A They directly activate proto-oncogenes
- B They trigger crisis with breakage-fusion-bridge cycles promoting genomic instability ✓
- C They inhibit p53-mediated apoptosis
- D They promote angiogenesis via HIF-1α
Correct answer: B. They trigger crisis with breakage-fusion-bridge cycles promoting genomic instability
Explanation
Critically short telomeres lose their capping function and are recognized as DNA double-strand breaks. In cells with defective checkpoints (p53 mutant), these uncapped ends fuse, creating dicentric chromosomes that undergo breakage-fusion-bridge (BFB) cycles during mitosis, generating massive genomic instability and gene amplifications. This genomic crisis paradoxically accelerates carcinogenesis by creating diverse mutations, after which telomerase reactivation stabilizes the genome in the selected malignant clone.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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