title: Genetic analysis of multifocal superficial urothelial cancers by array-based comparative genomic hybridisation.
abstract: The purpose of this study was to investigate the accumulation of genetic alterations during metachronous and/or synchronous development of multifocal low-grade superficial urothelial tumours in the same patient, by using array-based comparative genomic hybridisation (array-CGH) and FGFR mutation analysis. We analysed 24 tumours (pTa-1 G1-2) from five patients. We had previously identified a clonal relationship among the tumours of each patient by microsatellite analysis. This time, unsupervised hierarchical cluster analysis revealed that the tumours from each patient were clustered together independently of the tumours from the other patients. All of the tumours from a single patient showed a set of 2-7 identical regional or whole-arm chromosomal changes. In addition, several individual alterations were also found. Cladistic diagrams revealed that the accumulation of genetic alterations could not be explained by a linear model, and the existence of a hypothetical precursor cell was assumed in four patients. In some cases, FGFR mutation seemed to occur later during multifocal tumour development. Taken together, these findings suggest that low-grade superficial urothelial tumours accumulate minor genetic alterations during multifocal development, although these tumours are genetically stable.
authors.affiliation: Department of Urology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kawanishi
authors.forename: T
authors.initials: T
authors.lastname: Takahashi
authors.forename: M
authors.initials: M
authors.lastname: Ito
authors.forename: Y
authors.initials: Y
authors.lastname: Matsui
authors.forename: J
authors.initials: J
authors.lastname: Watanabe
authors.forename: N
authors.initials: N
authors.lastname: Ito
authors.forename: T
authors.initials: T
authors.lastname: Kamoto
authors.forename: T
authors.initials: T
authors.lastname: Kadowaki
authors.forename: G
authors.initials: G
authors.lastname: Tsujimoto
authors.forename: I
authors.initials: I
authors.lastname: Imoto
authors.forename: J
authors.initials: J
authors.lastname: Inazawa
authors.forename: H
authors.initials: H
authors.lastname: Nishiyama
authors.forename: O
authors.initials: O
authors.lastname: Ogawa
mesh_terms: D002877:Chromosomes, Human / Q000235:genetics; D004252:DNA Mutational Analysis; D018450:Disease Progression; D006801:Humans; D016296:Mutagenesis; D020411:Oligonucleotide Array Sequence Analysis; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics*; D014571:Urologic Neoplasms / Q000235:genetics* / Q000473:pathology; D019459:Urothelium / Q000378:metabolism / Q000473:pathology
chemical_list: C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3