Bladder Cancer in the Genomic Era

Context.-Bladder cancer is a heterogeneous disease that exhibits a wide spectrum of clinical and pathologic features. The classification of bladder cancer has been traditionally based on morphologic assessment with the aid of immunohistochemistry. However, recent genomic studies have revealed that distinct alterations of DNA and RNA in bladder cancer may underlie its diverse clinicopathologic features, leading to a novel molecular classification of this common human cancer. Objective.-To update recent developments in genomic characterization of bladder cancer, which may shed insights on the molecular mechanisms underlying the origin of bladder cancer, dual-track oncogenic pathways, intrinsic molecular subtyping, and development of histologic variants. Data Sources.-Peer-reviewed literature retrieved from PubMed search and authors' own research. Conclusions.-Bladder cancer is likely to arise from different uroprogenitor cells through papillary/luminal and nonpapillary/basal tracks. The intrinsic molecular subtypes of bladder cancer referred to as luminal and basal exhibit distinct expression signatures, clinicopathologic features, and sensitivities to standard chemotherapy. Genomic characterization of bladder cancer provides new insights to understanding the biological nature of this complex disease, which may lead to more effective treatment.