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Bladder cancer is a common malignancy in the United States and is estimated to affect 81 190 new patients and to cause 17 240 deaths in 2018. (1) Among a [...], * 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. doi: 10.5858/arpa.2018-0329-RA

Introduction NOTCH is a single-pass transmembrane receptor activated by interaction with transmembrane ligands of the DSL (Delta-like and Jagged) family present on the membrane of neighboring cells. There are 4 [...], NOTCH signaling suppresses tumor growth and proliferation in several types of stratified epithelia. Here, we show that missense mutations in NOTCH1 and NOTCH2 found in human bladder cancers result in loss of function. In murine models, genetic ablation of the NOTCH pathway accelerated bladder tumorigenesis and promoted the formation of squamous cell carcinomas, with areas of mesenchymal features. Using bladder cancer cells, we determined that the NOTCH pathway stabilizes the epithelial phenotype through its effector HES1 and, consequently, loss of NOTCH activity favors the process of epithelial-mesenchymal transition. Evaluation of human bladder cancer samples revealed that tumors with low levels of HES1 present mesenchymal features and are more aggressive. Together, our results indicate that NOTCH serves as a tumor suppressor in the bladder and that loss of this pathway promotes mesenchymal and invasive features.

Author(s): A Iwaniuk[sup.1] , M Owczarek[sup.1] , M PietrusiÅski[sup.2] , E Borkowska[sup.2] , M Rozniecki[sup.5] , M Borowiec[sup.2] , M Sosnowski[sup.3] , J Kocki[sup.4] and B KaÅużewski[sup.1] The pilot study [...]

Author(s): Jeanne Erdmann [sup.1] Author Affiliations: (1) science journalist based near St Louis, St Louis, Inspiration can strike at any time. For Dan Theodorescu, it came during his half-hour commute [...], Researchers delving into the details of bladder cancer are finding a rich trove of genetic information.