Epidemiologic studies of hepatocellular carcinoma in regions with high dietary contamination by Aspergillus flavus identified a characteristic molecular signature in the resulting tumors. This signature is:

• A CTNNB1 exon 3 activating mutation
• B Homozygous deletion of CDKN2A
• C Mutation of TP53 at codon 249 (arginine to serine) ✓
• D TERT promoter mutation

Explanation

Aflatoxin B1, produced by Aspergillus species contaminating stored grains and peanuts, forms DNA adducts that cause a highly characteristic TP53 missense mutation at codon 249, substituting serine for arginine. This mutation is found at high frequency in HCC from sub-Saharan Africa and China where dietary aflatoxin exposure coexists with hepatitis B. TERT promoter mutations are the commonest alteration in HCC overall but are not specific to aflatoxin, while CTNNB1 mutations relate to metabolic risk factors.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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