Which mutation is associated with urothelial carcinomas?

• A. KRAS
• B. NTRK
• C. TP53
• D. BRCA1

Answer: (C)

Mutations that inactivate the p53 tumor suppressor are strongly linked to urothelial carcinomas, especially the high‑grade, muscle‑invasive form. The TP53 gene encodes p53, which acts as the guardian of the genome by halting the cell cycle to repair DNA or by triggering cell death when damage is too great. When TP53 is mutated, this safety check fails, allowing cells with genetic errors to continue dividing and accumulate further changes that drive more aggressive, invasive cancer. In bladder/urothelial cancers, tumors that progress to high grade and invade into the muscle commonly show TP53 alterations, whereas the more indolent, low‑grade papillary tumors often have FGFR3 mutations instead. So, among the options, TP53 is the mutation most characteristically associated with urothelial carcinomas.