Chromosomal analysis of bladder cancer. III. Nonrandom alterations

Smeets, Wim; Pauwels, R.P.E.; Laarakkers, Lisette; Debruyne, F.M.J.; Geraedts, J. P. M.

doi:10.1016/0165-4608(87)90028-8

Cited by 91 publications

(44 citation statements)

References 25 publications

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“…The alterations range from monosomies as sole cytogenetic abnormalities to allelic losses that were initially reported to be present in 67% of advanced bladder cancers (Gibas et al, 1984;Smeets et al, 1987;Vanni et al, 1988;Atkin and Baker 1985;Babu et al, 1987;Berger et al, 1986). Some studies have shown that allelic losses on 9q are the most frequent and appear in tumors of all histologic grades and stages (Olumi et al, 1990).…”

Section: Discussionmentioning

confidence: 99%

Superimposed histologic and genetic mapping of chromosome 9 in progression of human urinary bladder neoplasia: implications for a genetic model of multistep urothelial carcinogenesis and early detection of urinary bladder cancer

et al. 1999

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The evolution of alterations on chromosome 9, including the putative tumor suppressor genes mapped to the 9p21-22 region (the MTS genes), was studied in relation to the progression of human urinary bladder neoplasia by using whole organ superimposed histologic and genetic mapping in cystectomy specimens and was veri®ed in urinary bladder tumors of various pathogenetic subsets with longterm follow-up. The applicability of chromosome 9 allelic losses as non-invasive markers of urothelial neoplasia was tested on voided urine and/or bladder washings of patients with urinary bladder cancer. Although sequential multiple hits in the MTS locus were documented in the development of intraurothelial precursor lesions, the MTS genes do not seem to represent a major target for p21-23 deletions in bladder cancer. Two additional tumor suppressor genes involved in bladder neoplasia located distally and proximally to the MTS locus within p22-23 and p11-13 regions respectively were identi®ed. Several distinct putative tumor suppressor gene loci within the q12-13, q21-22, and q34 regions were identi®ed on the q arm. In particular, the pericentromeric q12-13 area may contain the critical tumor suppressor gene or genes for the development of early urothelial neoplasia. Allelic losses of chromosome 9 were associated with expansion of the abnormal urothelial clone which frequently involved large areas of urinary bladder mucosa. These losses could be found in a high proportion of urothelial tumors and in voided urine or bladder washing samples of nearly all patients with urinary bladder carcinoma.

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Section: Discussionmentioning

confidence: 99%

Superimposed histologic and genetic mapping of chromosome 9 in progression of human urinary bladder neoplasia: implications for a genetic model of multistep urothelial carcinogenesis and early detection of urinary bladder cancer

et al. 1999

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“…A surprising result of this study was that the occurrence of microsatellite alterations was more frequent in low-grade and low-stage tumors (Table 2), although the difference did not reach statistical significance, and in a univariate analysis was predictor of a longer disease-free survival and a reduced risk of disease progression (Figures 2c and 3c). Frequent occurrence of loss of microsatellites has been described in bladder urothelial carcinomas 5 and LOH has been reported to occur on several chromosomes [5][6][7]8 in both superficial (pTa-T1) and muscle-invasive, but no data are available on its frequency in bladder cancers arising at young age. As far as microsatellite instability is concerned, conflicting data have been reported in the literature about bladder cancers with mutation frequencies ranging from 0 to 100%.…”

Section: Discussionmentioning

confidence: 99%

“…5 Loss of microsatellites has been used as a marker of loss of heterozygosity (LOH) and has been shown to involve several loci throughout the genome 6,7 with chromosome 9 being the most frequently altered in both superficial (pTa-T1) and muscle-invasive bladder cancers. 8 The accumulation of mutations in microsatellite sequences throughout the genome is known as microsatellite instability.…”

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confidence: 99%

Prevalence and prognostic significance of microsatellite alterations in young patients with bladder cancer

et al. 2005

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Mutations in microsatellite sequences are a hallmark of neoplastic transformation and have been reported in the majority of human cancers. Conflicting results have been reported on the role of microsatellite alterations in bladder tumorigenesis and it has been suggested that they might be mainly involved in the development of bladder cancers in young patients. In this study, DNA was extracted from laser-microdissected samples of 51 superficial papillary bladder urothelial carcinomas arising in young patients and was analyzed for the status of 19 microsatellite loci previously reported to be associated with bladder tumorigenesis. The occurrence and the pattern of microsatellite alterations, in form of loss or length variation, was evaluated and correlated with other clinicopathologic and molecular markers. The prognostic significance of these alterations was also evaluated. Loss of heterozygosity at one or more loci was detected in all 51 tumors analyzed. Length variation in at least one locus was observed in 48 (94%) of the cases. The microsatellite that was more frequently altered was D11S488 (69%), followed by D9S162 (61%), D3S3050 (55%), D3S1300 (51%) and D4S243 (51%), all the remaining being altered in less than 50% of cases. The occurrence of microsatellite alterations was not associated with tumor grade nor with tumor stage, the expression of p53, cyclin D1 or the cyclin-dependent kinase-inhibitor p27Kip1 while it was significantly more frequent in tumors with increased expression of the proliferation marker MIB-1 (P ¼ 0.003). The occurrence of alterations at the analyzed loci was associated with a reduced risk of tumor recurrence (P ¼ 0.04 by log-rank test) and disease progression (P ¼ 0.02) in a univariate analysis. These findings demonstrate that microsatellite alterations are frequent and early events and might have a prognostic significance in bladder cancers arising at young age.

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“…In spite of numerous research eorts, little is known about the molecular basis of bladder cancer. Cytogenetic studies of primary bladder cancer have identi®ed recurrent karyotypic aberrations, including i(5p), +7, 79, and del(11p), as well as deletions on chromosome 10q (Gibas et al, 1984;Berger et al, 1986;Babu et al, 1987;Smeets et al, 1987;Vanni et al, 1988). Others reported structural abnormalities involving chromosomes 1, 3, 8 and 17 (Sandberg, 1990).…”

Section: Introductionmentioning

confidence: 99%

Cluster of allele losses within a 2.5 cM region of chromosome 10 in high-grade invasive bladder cancer

et al. 1998

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Chromosomal analysis of bladder cancer. III. Nonrandom alterations

Cited by 91 publications

References 25 publications

Superimposed histologic and genetic mapping of chromosome 9 in progression of human urinary bladder neoplasia: implications for a genetic model of multistep urothelial carcinogenesis and early detection of urinary bladder cancer

Superimposed histologic and genetic mapping of chromosome 9 in progression of human urinary bladder neoplasia: implications for a genetic model of multistep urothelial carcinogenesis and early detection of urinary bladder cancer

Prevalence and prognostic significance of microsatellite alterations in young patients with bladder cancer

Cluster of allele losses within a 2.5 cM region of chromosome 10 in high-grade invasive bladder cancer

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