Epidemiological studies of dietary aflatoxin B1 exposure in regions endemic for hepatocellular carcinoma have demonstrated a characteristic molecular signature in the resulting tumours. This signature is:
- A Amplification of the MYC oncogene at chromosome 8q24
- B Activation of beta-catenin gene through exon 3 mutation
- C Mutation of p53 at codon 249 causing substitution of serine for arginine ✓
- D Hypermethylation of the p16 promoter region
Correct answer: C. Mutation of p53 at codon 249 causing substitution of serine for arginine
Explanation
Aflatoxin B1 metabolites form DNA adducts that produce a highly specific G to T transversion in the p53 tumour suppressor gene at codon 249, replacing arginine with serine, the so-called R249S mutation. This signature is virtually diagnostic of aflatoxin exposure and acts synergistically with chronic hepatitis B in hepatocarcinogenesis. Beta-catenin mutations characterise some hepatocellular adenomas and well-differentiated HCC unrelated to aflatoxin, while MYC amplification and p16 methylation lack this geographic specificity.
Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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