A 65-year-old man with hepatocellular carcinoma has markedly elevated serum alpha-fetoprotein (AFP). AFP re-expression in HCC results primarily from:
- A Demethylation of AFP gene promoter with transcriptional reactivation ✓
- B Chromosomal amplification of chromosome 4q
- C Post-translational modification of albumin
- D Oncogene-driven AFP secretion from stromal cells
Correct answer: A. Demethylation of AFP gene promoter with transcriptional reactivation
Explanation
AFP is normally produced by fetal hepatocytes and yolk sac but is epigenetically silenced in adult liver by promoter methylation. In hepatocellular carcinoma, global DNA hypomethylation leads to demethylation of the AFP promoter, reactivating its transcription. This oncofetal protein is therefore a useful tumour marker for HCC and non-seminomatous germ cell tumours. Chromosomal amplification and stromal secretion are not the primary mechanism.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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