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The objectives of this review were to summarize the most important oncogenes and tumor suppressor genes involved in urothelial carcinoma and to address their role in pathogenesis, their prognostic value, and their potential use as therapeutic targets. The collected data led the authors to propose a common pathway in which the fibroblastic growth factor receptor 3 (<jats:italic>FGFR3<\/jats:italic>) mutation seems to be the earliest genetic abnormality responsible for the transformation from normal tissue to atypia and dysplasia. Three different progression pathways were proposed: The first operative pathway is from dysplasia to superficial papillary pathologic Ta (pTa) tumors to pT1 tumors and, ultimately, to pT2 tumors with <jats:italic>FGFR3<\/jats:italic> and tuberous sclerosis complex 1 (<jats:italic>TSC1<\/jats:italic>) the responsible genes. The second major operative pathway is from dysplasia, to carcinoma in situ, and to solid pT1 and pT2 tumors. The third pathway of progression is from dysplasia to papillary T1 and pT2 tumors. The genes involved in the last 2 pathways are the <jats:italic>p53<\/jats:italic>, serine threonine protein kinase 15 (<jats:italic>STK15<\/jats:italic>), triple\u2010function domain (<jats:italic>TRIO<\/jats:italic>), fragile histidine triad (<jats:italic>FHIT<\/jats:italic>), <jats:italic>p63<\/jats:italic> genes; and alterations of 20q and 5p, alterations of adhesions, angiogenesis, and matrix\u2010remodeling gene products also are involved. Finally, murine leukemia viral oncogene homologue 1 (<jats:italic>RAF1<\/jats:italic>) and <jats:italic>CD9<\/jats:italic> are involved in the progression from papillary pT1 tumors to pT2 tumors. Cancer 2006. \u00a9 2006 American Cancer Society.<\/jats:p>","DOI":"10.1002\/cncr.21743","type":"journal-article","created":{"date-parts":[[2006,2,9]],"date-time":"2006-02-09T15:55:45Z","timestamp":1139500545000},"page":"1205-1216","source":"Crossref","is-referenced-by-count":67,"title":["Genetic alterations in urothelial bladder carcinoma"],"prefix":"10.1002","volume":"106","author":[{"given":"Paulette","family":"Mhawech\u2010Fauceglia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard 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