A 60-year-old man with chronic pancreatitis and weight loss undergoes CT showing a mass in the head of the pancreas with upstream ductal dilation. CA 19-9 is elevated. The most common molecular alteration found in early pancreatic intraepithelial neoplasia (PanIN) is:

• A TP53 mutation
• B KRAS point mutation at codon 12 ✓
• C SMAD4 (DPC4) deletion
• D BRCA2 mutation

Explanation

KRAS oncogene point mutations (codon 12) are the earliest and most frequent molecular alteration in pancreatic ductal adenocarcinoma, found in >90% of cases and detectable even in PanIN-1 lesions. They activate constitutive RAS signalling. TP53 and SMAD4 mutations occur later in progression; BRCA2 germline mutations increase susceptibility but are not the initiating event in most sporadic cases.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.