Genomic Characteristics of Bladder Cancer: An AACR Project GENIE Study

Bladder and urothelial carcinoma are marked by profound genomic diversity. Using a large, multi-institutional dataset, we performed comprehensive genomic profiling of 4631 tumor samples from 4050 individuals. A retrospective analysis of bladder and urothelial cancer was performed using the AACR Project GENIE database. Demographic associations, mutation frequencies, copy number changes, and survival correlations were analyzed with a <i>p</i>-value < 0.05. Frequent mutations were identified in <i>TP53</i>, <i>TERT</i>, <i>KDM6A</i>, <i>KMT2D</i>, <i>ARID1A</i>, and <i>FGFR3</i>. Mutation frequencies varied by sex and race, with specific alterations enriched in female and Asian patients. Distinct patterns of co-occurrence, including <i>TP53</i> with <i>RB1</i>, and mutual exclusivity, including <i>TP53</i> with <i>FGFR3</i> or <i>KDM6A</i>, revealed distinct molecular subtypes. This study highlights the extensive heterogeneity of bladder cancer, and our findings emphasize the clinical importance of molecular stratification and support the need for further mechanistic and prospective studies to inform the development of targeted therapies.