The Knudson two-hit hypothesis of tumor suppressor gene inactivation is best illustrated by which pair of clinical scenarios?
- A APC mutation in FAP vs. KRAS mutation in sporadic colon cancer
- B BCR-ABL translocation in CML vs. c-MYC amplification in Burkitt lymphoma
- C Familial retinoblastoma (germline RB1 mutation) presenting at younger age vs. sporadic retinoblastoma presenting later and unilaterally ✓
- D TP53 missense mutation causing gain-of-function vs. loss-of-function
Correct answer: C. Familial retinoblastoma (germline RB1 mutation) presenting at younger age vs. sporadic retinoblastoma presenting later and unilaterally
Explanation
Knudson's model predicts that one hit is inherited (germline) and a second somatic hit is required for tumor formation. Familial retinoblastoma patients carry one germline RB1 mutation, need only one somatic hit, so tumors appear earlier and are bilateral/multifocal. Sporadic cases require two independent somatic hits, leading to unilateral, later-onset disease. Options B–D describe oncogene activation, not the classic two-hit tumor suppressor model.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.