A molecular study of colorectal carcinoma reveals that tumor suppressor gene inactivation requires mutation of both alleles. This concept, originally proposed based on retinoblastoma genetics, is best described by which term?
- A Oncogene addiction
- B Loss of heterozygosity
- C Knudson two-hit hypothesis ✓
- D Synthetic lethality
Correct answer: C. Knudson two-hit hypothesis
Explanation
Knudson's two-hit hypothesis states that both alleles of a tumor suppressor gene must be inactivated for tumor suppression to be lost. In hereditary retinoblastoma, one mutation is germline (first hit) and the second is somatic; in sporadic tumors, both hits are somatic. Loss of heterozygosity is the mechanism by which the second allele is lost, not the overarching concept itself.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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