Which mutation is associated with colon adenocarcinoma?

• A. NTRK1
• B. KRAS
• C. SMAD4
• D. MYC

Answer: (B)

Mutations in KRAS activate the Ras/MAPK signaling pathway, which drives cell growth in colorectal cancer. In colon adenocarcinoma, activating KRAS mutations are among the most common genetic changes, causing KRAS to stay in the GTP-bound active state and push cells to proliferate regardless of external growth signals. This not only helps explain tumor growth but also why these tumors often do not respond to anti-EGFR therapies, since blocking EGFR can’t shut down downstream KRAS-driven signaling. While other genes can be altered in colorectal cancer—NTRK1 fusions can occur in various tumors, SMAD4 loss is a later event affecting TGF-beta signaling, and MYC alterations can appear in cancers—the classic association with colon adenocarcinoma is a KRAS mutation.