| Abstract | Knowledge of the molecular subtypes of bladder cancer enables powerful generalizations involving the distinctive biology and pathways driving different disease subsets. Areas covered: In this review, we summarize the findings of a number of published studies exploring the molecular landscape of bladder cancer by analysis of genomic data from The Cancer Genome Atlas (TCGA). TCGA project has provided a comprehensive data resource of 412 muscle-invasive bladder cancers as characterized by multiple molecular analytical platforms. These data have been and will continue to be utilized in numerous subsequent studies aimed at better understanding the molecular basis of bladder cancer. The catalog of DNA-level alterations can greatly inform personalized and precision medicine approaches. Molecular subtypes of bladder cancer include distinct 'basal/squamous' and 'luminal' subtypes, cancers with papillary histology, disease subsets with prominent leukocyte infiltration and immune checkpoint marker expression, and a 'neuronal' subtype lacking small cell or neuroendocrine histology. The gene-level alterations and subtypes as revealed by TCGA data are relevant from the standpoint of both basic biology and clinical trial studies. Expert commentary: Multiple studies analyzing TCGA muscle-invasive bladder cancer cases point to the existence of five major expression-based molecular subtypes of the disease, with these subtypes having therapeutic implications.
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