Which mutation is associated with pancreatic adenocarcinoma?

• A. TP53
• B. BRCA2
• C. ALK
• D. KRAS

Answer: (D)

KRAS mutations are a defining feature of pancreatic adenocarcinoma. In pancreatic ductal adenocarcinoma, KRAS is mutated in the vast majority of tumors, often early in development, which leads to constitutive activation of the KRAS protein. This keeps the RAS/MAPK signaling pathway on continuously, driving unchecked cell growth and survival. Because of its high frequency and early role in initiating pancreatic cancer, the KRAS mutation is the best association for this cancer type.

TP53 mutations do occur and contribute to disease progression, but they are not as universally present as KRAS. BRCA2 mutations (germline or somatic) raise risk and have implications for therapy, but they are less common as a driver across most pancreatic cancers. ALK rearrangements are not typical drivers of pancreatic adenocarcinoma and are more characteristic of other cancer types.