Which gene is associated with urothelial carcinomas among the listed mutations?

• A. KRAS
• B. NTRK
• C. PTEN
• D. FGFR3

Answer: (D)

FGFR3 mutations are a well-known molecular feature of urothelial carcinoma. FGFR3 encodes a receptor tyrosine kinase, and activating mutations (often in non-muscle-invasive bladder cancers) drive signaling through pathways like MAPK and PI3K-AKT, promoting cell growth and survival. This strong association with urothelial tumors is why FGFR3 is singled out for this cancer type, and it also underpins targeted therapies using FGFR inhibitors for tumors that harbor these alterations. In contrast, KRAS mutations are more characteristic of other cancers (such as colorectal, pancreatic, and lung), NTRK fusions occur across various tumors but aren’t specifically linked to urothelial carcinoma, and PTEN mutations are common across many cancer types as a tumor suppressor loss. The clear and consistent link between urothelial carcinomas and FGFR3 mutations makes it the best fit.