A 62-year-old man with hepatocellular carcinoma has serum AFP of 850 ng/mL. Which molecular mechanism most directly drives AFP re-expression in HCC?

• A Amplification of chromosome 4q
• B Point mutation in the AFP coding sequence
• C PTEN loss causing mTOR hyperactivation
• D Demethylation of the AFP gene promoter CpG islands ✓

Explanation

AFP is normally silenced in adult hepatocytes by promoter CpG island methylation. In HCC, aberrant demethylation of the AFP promoter allows re-expression of this fetal protein. AFP re-expression is a classic example of epigenetic derepression of oncofetal antigens. Amplification, coding mutations, and PTEN loss do not directly drive AFP promoter re-activation.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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