The Knudson two-hit hypothesis for tumor suppressor gene inactivation was originally proposed based on statistical analysis of which childhood tumor?
- A Retinoblastoma ✓
- B Wilms tumor
- C Medulloblastoma
- D Neuroblastoma
Correct answer: A. Retinoblastoma
Explanation
Knudson's two-hit hypothesis was derived from epidemiological data comparing bilateral (familial) versus unilateral (sporadic) retinoblastoma, proposing that both alleles of RB1 must be inactivated for tumor development. In familial cases, the first hit is germline; the second somatic hit completes tumor suppressor loss. Wilms tumor also follows a two-hit model (WT1) but was not the basis of the original hypothesis.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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