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KMID : 0377519950200040319
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Chung-Ang Journal of Medicine
1995 Volume.20 No. 4 p.319 ~ p.331
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Study of Clonality of Multifocal Urothelial Cancers
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Park Sung-Ho
Moon Woo-Chul
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Abstract
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Urothelial cancers are characterized by multifocal development at different locations and/or time. There are two hypothesis for the mechanism of multifocal develoment of urothelial cancer : One is a field cancerization hypothesis and the other is a clonal origin hypothesis. Mutations in the p53 tumor suppressor gene are one the most common genetic alterations of urothelial cancers. In order to identify mechanism of mulifocal development of urotherlial cancers, we analyzed mutations in the p53 gene in 5 patients who presented with both upper urinary tract urothelial cancers and lower urinary tract urotheoial cancers. DNA was extracted from 13 paraffin-embedded specimens of upper and lower urothelial cancers. DNA from exon 5-8 of the p53 gene were analyzed by the polymerase chain reaction-single strand conformation polymorphism(PCR-SSCP) technique to screen the presence of mutations of the gene. DNA from 3 patients were also sequenced by subcloning into T7Blue vector followed by dideoxy chain termination method to confirm the presence of mutations and determine the base substitution were exon 5(codon 126, 159) or 8(codon 270). Mutation affected G or C base and the pattern of mutations were missence or nonsense mutation. Remarkably, in all of 2 cases the location and the base substitution profile of the mutation in the upper urothelial cancer were identical to those of the lower urothelial cancers. These preliminary results suggest that multifocal develoment of urothelial cancers may be clonal in origin and occur due to implantation of primary cancer cells. This study could provide the new approach for early detection and treatment of second primary urothelial cancers.
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KEYWORD
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urothelial cancer, multifocal, p53, mutation, clonal
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