Knudson's 'two-hit hypothesis' in retinoblastoma predicts that hereditary cases will:
- A Affect only one eye with a single somatic mutation
- B Require three sequential mutations for tumor development
- C Be bilateral and multifocal, with germline RB1 mutation as the first hit and somatic mutation as the second hit ✓
- D Present later in life than sporadic cases due to immune tolerance
Correct answer: C. Be bilateral and multifocal, with germline RB1 mutation as the first hit and somatic mutation as the second hit
Explanation
Knudson's two-hit hypothesis states that two mutations in both alleles of the RB1 tumor suppressor gene are required for retinoblastoma development. In hereditary cases, the first hit is a germline mutation present in every cell, so only one additional somatic mutation is needed in any retinal cell, making bilateral, multifocal tumors statistically likely at an earlier age. Sporadic cases require two independent somatic mutations in the same cell, are typically unilateral and unifocal, and present later.
Reference: Khurana Comprehensive Ophthalmology, 7th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.