Which mechanism best explains how a loss-of-function mutation in a tumor suppressor gene requires both alleles to be inactivated before neoplastic transformation (Knudson's two-hit hypothesis)?
- A Tumor suppressors act in a dominant-negative fashion
- B One wild-type allele provides sufficient gene product to suppress tumor growth; loss of both alleles removes this suppression ✓
- C Haploinsufficiency always causes immediate transformation
- D The second hit always involves chromosomal translocation
Correct answer: B. One wild-type allele provides sufficient gene product to suppress tumor growth; loss of both alleles removes this suppression
Explanation
Tumor suppressor genes follow a recessive pattern at the cellular level. A single functional allele produces enough protein to maintain growth control (haploinsufficiency is the exception, not the rule). Only when both alleles are inactivated — the two hits — is suppressor function lost and transformation enabled. This explains the hereditary retinoblastoma pattern where the first hit is germline and the second is somatic.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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