title: Superficial and metachronous invasive bladder carcinomas are clonally related.
abstract: Synchronous and metachronous tumors are frequently observed in the urinary tract and may be explained by the concept of 'field cancerization,' i.e., exposure to carcinogens leading to the independent transformation of many urothelial cells resulting in oncogenetically unrelated tumors. Increasing evidence, however, supports the concept of clonality, i.e., the progeny of a single transformed cell spreads through the urinary system resulting in genetically related tumors. The aim of our study was to investigate the putative clonal origin of invasive urothelial cell carcinomas (UCCs) of the bladder from a prior superficial tumor. We selected 6 patients (5 males and 1 female) with superficial and subsequent invasive UCC tumors. All patients were previously diagnosed with a p53 mutation in their invasive tumor. At least 1 superficial and 1 invasive tumor of the same patient were analyzed for mutations in the p53 tumor suppressor gene by PCR-SSCP and, in case of a band shift, followed by direct sequencing. In all patients the same p53 mutation was found in the superficial and subsequent invasive tumor(s). All tumors arose from the same progenitor cell. These results support the concept of a clonal origin of superficial and metachronous invasive bladder UCCs.
authors.affiliation: Department of Urology, University Medical Centre Nijmegen, The Netherlands.
authors.forename: J L
authors.initials: JL
authors.lastname: Vriesema
authors.forename: K K
authors.initials: KK
authors.lastname: Aben
authors.forename: J A
authors.initials: JA
authors.lastname: Witjes
authors.forename: L A
authors.initials: LA
authors.lastname: Kiemeney
authors.forename: J A
authors.initials: JA
authors.lastname: Schalken
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D016609:Neoplasms, Second Primary / Q000235:genetics* / Q000473:pathology; D018807:Polymorphism, Single-Stranded Conformational; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53