Comprehensive Genomic Sequencing of Urothelial Tumors Identifies Rare SMARCB1 (INI-1)–Deficient Carcinomas of the Urinary System

Comprehensive genomic profiling of urothelial carcinoma (n = 1287) reveals a subset (∼0.3%) of urinary tract tumors driven by complete loss of function of the SMARCB1(switch/sucrose nonfermentable-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1) gene. The tumors are genomically and clinically distinct from conventional urothelial carcinoma, with limited additional genomic drivers, a low tumor mutational burden, an earlier presentation in life, and a female preponderance. Optimum benefit might be derived from nonconventional therapy.