In a multistep colorectal carcinogenesis model, the APC gene mutation is the initiating event. APC protein normally functions by:

• A Activating RAS-MAP kinase signalling
• B Promoting degradation of beta-catenin in the cytoplasm ✓
• C Inhibiting MDM2-mediated p53 degradation
• D Facilitating DNA mismatch repair

Explanation

APC is a component of the destruction complex that targets beta-catenin for proteasomal degradation, keeping the Wnt pathway off. Loss of APC leads to beta-catenin accumulation and nuclear translocation, driving transcription of growth-promoting genes. RAS-MAP kinase is activated later by KRAS mutations; MDM2/p53 is a separate pathway; DNA mismatch repair deficiency underlies microsatellite instability, a different pathway.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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