Which of the following tumor suppressor genes demonstrates 'loss of heterozygosity' as its second hit in familial adenomatous polyposis?

• A APC ✓
• B BRCA1
• C TP53
• D VHL

Explanation

Familial adenomatous polyposis is caused by germline mutations in the APC tumor suppressor gene on chromosome 5q. Per Knudson's two-hit hypothesis, the inherited mutant allele is one hit; somatic loss of heterozygosity (deletion or mutation of the second allele) in a single colonic epithelial cell is the second hit that initiates adenoma formation. APC normally promotes beta-catenin degradation, and its loss leads to constitutive Wnt signaling.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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