Which molecular alteration is present in >90% of pancreatic ductal adenocarcinomas and is detectable in the earliest precursor lesion (PanIN-1)?
- A KRAS codon 12 activating point mutation ✓
- B SMAD4 (DPC4) deletion
- C TP53 mutation
- D CDKN2A (p16) deletion
Correct answer: A. KRAS codon 12 activating point mutation
Explanation
KRAS codon 12 mutations (most commonly G12D) are the earliest and most common genetic event in pancreatic ductal carcinogenesis, present in >90% of invasive carcinomas and detectable in PanIN-1 lesions. CDKN2A loss occurs in PanIN-2; TP53 and SMAD4 mutations occur late, in PanIN-3 and invasive carcinoma. This sequential accumulation mirrors the colorectal adenoma-carcinoma sequence.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.