Oncogene-driven genomic profiles are linked to poor overall survival in muscle-invasive bladder cancer (MIBC)

Abstract Purpose Muscle-invasive bladder cancer (MIBC) is a genomically complex disease with limited biomarkers for predicting patient outcomes. This study aimed to identify molecular correlates of overall survival in MIBC through comprehensive genomic profiling. Methods Tumor DNA from cystectomy specimens of 32 MIBC patients was analyzed using the FoundationOne® CDx platform. Patients were categorized into a favorable outcome group (overall survival ≥ 60 months, n = 14) and a poor outcome group (overall survival < 60 months, n = 18). Mutational profiles, genomic instability markers, and copy number alterations were compared between groups. Results Across the cohort, 279 pathogenic or likely pathogenic mutations were identified in 88 genes. Frequently altered genes—including TP53, PIK3CA, KDM6A, and FGFR3—showed similar distributions across outcome groups. Genomic instability markers, including tumor mutational burden (TMB) and microsatellite instability (MSI), were comparable and not prognostically informative. In contrast, tumors from the poor outcome group exhibited significantly higher frequency and burden of gene amplifications, often involving known oncogenes and co-amplification hotspots. Conclusion These exploratory findings suggest that oncogene amplifications, rather than traditional genomic instability metrics, are associated with poor overall survival in MIBC, warranting validation in larger cohorts to assess their potential relevance as prognostic markers and therapeutic targets.