title: The Emerging Molecular Landscape of Urothelial Carcinoma.
abstract: Although there have been many recent discoveries in the molecular alterations associated with urothelial carcinoma, current understanding of this disease lags behind many other malignancies. Historically, a two-pathway model had been applied to distinguish low- and high-grade urothelial carcinoma, although significant overlap and increasing complexity of molecular alterations has been recently described. In many cases, mutations in HRAS and FGFR3 that affect the MAPK and PI3K pathways seem to be associated with noninvasive low-grade papillary tumors, whereas mutations in TP53 and RB that affect the G1-S transition of the cell cycle are associated with high-grade in situ and invasive carcinoma. However, recent large-scale analyses have identified overlap in these pathways relative to morphology, and in addition, many other variants in a wide variety of oncogenes and tumor-suppressor genes have been identified. New technologies including next-generation sequencing have enabled more detailed analysis of urothelial carcinoma, and several groups have proposed molecular classification systems based on these data, although consensus is elusive. This article reviews the current understanding of alterations affecting oncogenes and tumor-suppressor genes associated with urothelial carcinoma, and their application in the context of morphology and classification schema.
authors: Department of Pathology, University of California, San Diego, 200 West Arbor Drive, La Jolla, CA 92103, USA.
authors: James P
authors: JP
authors: Solomon
authors: Division of Anatomic Pathology, Department of Pathology, University of California, San Diego, 9500 Gilman Drive, MC 0612, La Jolla, CA 92093, USA. Electronic address: dhansel@ucsd.edu.
authors: Donna E
authors: DE
authors: Hansel
mesh_terms: D002295:Carcinoma, Transitional Cell / Q000235:genetics / Q000473:pathology; D004252:DNA Mutational Analysis; D020022:Genetic Predisposition to Disease; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009154:Mutation / Q000235:genetics*; D009857:Oncogenes / Q000235:genetics; D010641:Phenotype; D011237:Predictive Value of Tests; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology*; D019459:Urothelium / Q000473:pathology*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3
keywords: Ancillary testing; Bladder cancer; Immunotherapy; Molecular pathology; Subclassification; Targeted therapy; Urothelial carcinoma