In the two-hit hypothesis of tumour suppressor gene inactivation, the 'first hit' in hereditary retinoblastoma is characterised by:

• A Somatic mutation in all retinal cells
• B Epigenetic silencing of both RB alleles
• C Loss of heterozygosity only in tumour cells
• D Germline mutation present in every cell of the body ✓

Explanation

In hereditary retinoblastoma, the first hit is a germline mutation in the RB1 gene inherited from a carrier parent, meaning every somatic cell carries one mutated allele. A second somatic mutation (second hit) in a retinal cell inactivates the remaining normal allele, causing tumour development. This explains the early-onset, multifocal, bilateral presentation in hereditary cases. Sporadic retinoblastoma requires two somatic hits in the same cell.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.