Urothelial Carcinoma in Children and Young Adults is Characterized by Higher Frequency of HRAS Mutations and Lower Prevalence of TERT Promoter and FGFR3 Mutations

Urothelial carcinoma in young patients is exceedingly rare, and their molecular oncogenesis is not well understood. In this study, we investigated the frequencies of HRAS, TERT promoter, and FGFR3 mutations in a cohort of 31 urothelial neoplasms occurring in children and young adults, to understand their molecular characteristics and underpinnings. Thirty-one urothelial neoplasms were identified in patients less than 30 years of age. Genomic DNA was extracted from formalin-fixed paraffin-embedded (FFPE) tissue sections. Real-time polymerase chain reaction was used to detect HRAS, TERT promoter, and FGFR3 mutations, and the results were analyzed using high-resolution fluorescence melting curves. The cohort included 2 urothelial papillomas, 1 papillary urothelial neoplasm of low malignant potential (PUNLMP), 23 noninvasive low-grade papillary urothelial carcinomas, and 5 noninvasive high-grade papillary urothelial carcinomas. The patients’ mean age was 18 years old, and the male-to-female ratio was 1.4:1. HRAS mutation was detected in 55.2% (16/29) of the premalignant/malignant cases and in 100% (2/2) of the urothelial papillomas, with an overall incidence of 58.1%. TERT promoter mutation was detected in 37.9% (11/29) of PUNLMP and malignant cases, and in none of the benign cases. FGFR3 mutation was not detected in any of the cases. Urothelial carcinomas occurring in children and young adults exhibit a distinct molecular profile compared with those in older patients, characterized by a higher frequency of HRAS mutations and a significantly lower prevalence of TERT promoter and FGFR3 alterations.