In areas of sub-Saharan Africa where dietary contamination with Aspergillus flavus is endemic, hepatocellular carcinomas show a characteristic mutation in the TP53 gene. Which alteration is most typical?
- A Missense mutation at codon 12 of KRAS
- B Deletion of exon 11 of BRCA1
- C G:C to T:A transversion at codon 249 of p53 ✓
- D Point mutation at codon 175 producing a nonsense stop codon
Correct answer: C. G:C to T:A transversion at codon 249 of p53
Explanation
Aflatoxin C1, produced by Aspergillus flavus, forms adducts with DNA and produces a highly characteristic G:B to T:A transversion at codon 249 of the TP53 gene in hepatocellular carcinoma. This specific fingerprint mutation is strong evidence that aflatoxin acts directly as a genotoxic initiator, acting synergistically with chronic hepatitis C infection in endemic regions. Codon 12 mutations belong to RAS genes, not p53, eliminating option A.
Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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