According to the classical adenoma-carcinoma sequence described by Fearon and Vogelstein, what is the correct temporal order of genetic events in the development of colorectal carcinoma?

• A KRAS mutation, then APC loss, then TP53 mutation
• B APC loss, then KRAS mutation, then TP53 mutation ✓
• C TP53 mutation, then KRAS mutation, then APC loss
• D APC loss, then TP53 mutation, then KRAS mutation

Explanation

In the chromosomal instability pathway, loss of APC occurs early and initiates adenoma formation, activation of KRAS follows and drives growth from small to larger adenoma, and TP53 mutation is a late event associated with transition from adenoma to carcinoma. Loss of SMAD4 and other changes accumulate along the way. Reversing the order confuses initiation with progression, since KRAS cannot drive tumour formation without prior APC loss.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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