The multi-hit model of carcinogenesis is best exemplified by which of the following hereditary tumor syndromes?

• A Li-Fraumeni syndrome (TP53 germline mutation)
• B Hereditary retinoblastoma (RB1 germline mutation) ✓
• C Familial adenomatous polyposis (APC germline mutation)
• D MEN type 1 (MEN1 germline mutation)

Explanation

Knudson's two-hit hypothesis was derived from analysis of hereditary retinoblastoma: one RB1 allele is mutated in the germline (first hit) and the second allele is lost somatically (second hit), inactivating the tumor suppressor. FAP also follows this model, but Knudson's original hypothesis was formulated specifically from retinoblastoma epidemiological data.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.