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Query: UMLS:C0005684 (bladder cancer)
 16,431 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The loss of DNA sequences on chromosomal bands 9p21-22 has been documented in a variety of malignancies including leukemias, gliomas, lung cancers, and melanomas. Because of the high incidence of monosomy 9 detected by both cytogenetics and loss of heterozygosity studies in bladder cancer, we examined seven bladder cancer cell lines for deletions in this region. Using seven DNA probes that span the region of 9p21-22 as well as a functional assay for methylthioadenosine phosphorylase (MTAP), which maps to 9p21, we found four cell lines that had small homozygous deletions. These deletions map centromeric to the interferon (IFN) gene cluster and telomeric to D9S171. Only one of the cell lines with deletions had a cytogenetically evident lesion in this chromosomal region. Preliminary loss of heterozygosity studies with 10 primary bladder cancer specimens using 10 markers spanning chromosome 9 revealed loss of heterozygosity at the IFN locus with retention of heterozygosity with more centromeric 9p markers and all informative 9q markers in the tumor of one patient. These data suggest that loss of a tumor suppressor gene on 9p21-22, which may represent a general pathway of oncogenesis, is important in bladder cancer development.
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PMID:Homozygous deletions within chromosomal bands 9p21-22 in bladder cancer. 751 8

Deletions of the short arm of chromosome 9 have been observed in a number of malignant cell lines and primary tumor samples using cytogenetic and molecular techniques. These tumors include acute lymphoblastic leukemias, lymphomas, gliomas, melanomas, mesotheliomas, bladder cancer, and lung cancer. The smallest region of overlap (SRO) of these deletions is thought to contain a tumor suppressor gene. A microdissection library was constructed from bands 9p21-p23 to obtain DNA probes that would be useful in further defining the limits of the deletions. Eight single-copy probes were found to be homozygously deleted in at least 1 of the 10 cell lines examined. The mapping of these 8 clones using a panel of cell lines with deletions revealed that 3 probes mapped telomeric to the SRO and 5 clones mapped centromeric to the SRO.
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PMID:Mapping a putative tumor suppressor gene on chromosome 9 bands p21-p22 with microdissection probes. 753 86

To examine the significance of Y chromosome losses in bladder cancer, fluorescence in situ hybridization (FISH) was used to determine its prevalence and associations with known parameters of malignancy. Cells were dissociated from formalin-fixed paraffin-embedded bladder tumors from 68 male patients and from 11 post-mortem bladder washes of male patients with a negative bladder cancer history, and were examined by FISH using centromeric probes for chromosomes X, Y, 7, 9, and 17. Nullisomy for chromosome Y was seen in 23 of 68 tumors (34%), monosomy in 28 of 68 tumors (41%), and polysomy in 17 of 68 tumors (25%). There was no association between chromosome Y loss and tumor grade, stage, tumor growth fraction (Ki67 LI), p53 immunostaining, and presence of p53 deletions. Patient age was higher for tumors with a Y loss (73.5 +/- 12.0 years) than for tumors without Y loss (66.6 +/- 10.8 years; p = 0.0207). In one normal bladder wash, a distinct subpopulation (38% of cells) with Y nullisomy was seen. These data suggest that Y loss is a frequent event that can occur early in bladder cancer, although there is no evidence for a role of Y loss in tumor progression.
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PMID:Y chromosome loss detected by FISH in bladder cancer. 766 48

Bladder irrigation specimens provide a sampling of the entire bladder urothelium and are the most practical sample for longitudinally monitoring patients. This study presents cross-sectional fluorescence in situ hybridization (FISH) analyses with correlated DNA cytometry data on 76 patients monitored for recurrent bladder tumors. FISH probes complementary to centromeric satellite sequences for chromosomes 1, 7, 9, 11, 15, and 17 were used. Aberrations in copy number were observed for chromosomes 1, 7, 11, and 17 principally in patients with aneuploid tumors. Monosomy of chromosome 9 was observed in 39% of the diploid and 31% of the specimens with high hyperdiploid fraction. Significantly, 24% of patients with a history of bladder cancer but with no clinical evidence of disease exhibited monosomy of chromosome 9. This suggests a persistent and significantly large population of abnormal cells in the absence of clinical evidence of disease. Loss of chromosome 9 relative to DNA ploidy was observed in 24% of patients with no evidence of disease, in 59% of patients with tumor, and in 79% of patients with histologically confirmed transitional cell carcinoma, grades 1-3. Loss of chromosome 15 was also observed in a large percentage of patients. Loss of chromosome 15 was observed in 41% of specimens from patients in whom no tumor was seen, in 38% of specimens from patients with tumor, and in 67% of specimens from patients with histologically confirmed transitional cell carcinoma. Results of this study document the use of bladder irrigation specimens as a specimen source for FISH analyses.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Bladder irrigation specimens assayed by fluorescence in situ hybridization to interphase nuclei. 787 39

Double-target in situ hybridization technique (ISH) was applied to 37 cases of bladder cancer to detect numerical aberrations of chromosomes 7, 9, 10, and 11 by centromeric DNA probes. Of 33 evaluable cases, 29 (88%) demonstrated chromosome aberrations. In 17 cases with diploid pattern as measured by flow-cytometric DNA analysis (FCM), 15 (88%) demonstrated chromosome aberrations. Of these, trisomy 7, monosomy 9, and trisomy 10 were detected in three, three, and one case, respectively, as a single chromosome aberration. In 14 (88%) of 16 cases with an aneuploid DNA pattern, chromosome aberrations for two or more chromosomes were demonstrated. A significant correlation was observed between grade of chromosome aberrations and tumor grade (p < 0.01, Fisher's test), between number of spots for chromosome 7 and peak value in FCM (p = 0.015, by Spearman rank order test). In eight cases, chromosome aberrations in the tumor were compared with the corresponding pattern in the grossly normal and histologically benign mucosa. Trisomy 10 and monosomy 9 were detected as chromosome numerical aberrations in the histologically normal mucosa, consistent with aberrations in the corresponding patients. We conclude that trisomy 7, monosomy 9, and trisomy 10 may be early events in the evolution of bladder cancer.
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PMID:Nonrandom numerical aberrations of chromosomes 7, 9, and 10 in DNA-diploid bladder cancer. 795 21

An allelotype analysis of transitional cell carcinoma of the bladder identified loss of heterozygosity (LOH) on chromosome arm 4p in 22% of tumours. In a more detailed LOH study of 178 bladder carcinomas, a 750 kb common region of deletion was identified between the markers D4S43 and D4S127 just telomeric to the Huntington disease locus. To refine this region of deletion at 4p16.3, we have carried out detailed fluorescence in situ hybridisation (FISH) analysis of 12 bladder cancer cell lines by using a chromosome 4 centromeric probe combined with a series of cosmid probes from contigs spanning the 750 kb region of deletion. A common 30 kb region of deletion was identified at 4p16.3 in over one-third of the bladder cancer cell lines analysed. The present study has refined the localisation of the critical region of deletion from 750 kb to approximately 30 kb, providing a precise starting point for positional cloning of the gene(s) involved in bladder cancer from within a very gene-rich region on chromosome band 4p16.3. This study demonstrates that FISH can be used for fine deletion mapping of potential tumour suppressor gene regions. The utilisation of FISH analysis to map chromosomal deletions should facilitate positional cloning of other genes as bacterial artificial chromosome (BAC) and yeast artificial chromosome (YAC) contigs of the human genome are established.
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PMID:Fluorescence in situ hybridization deletion mapping at 4p16.3 in bladder cancer cell lines refines the localisation of the critical interval to 30 kb. 1106 86

Inorganic arsenic is an established cause of lung and skin cancer. Epidemiological evidence from Taiwan suggests that arsenic causes more fatal internal cancers, with the highest relative risks reported for bladder cancer. We conducted a cross-sectional biomarker study in a Chilean male population chronically exposed to high (70 subjects) and low (55 subjects) arsenic levels in their drinking water (average concentrations, 600 and 15 micrograms As/liter, respectively). A fluorescent version of the exfoliated bladder cell micronucleus (MN) assay was used employing fluorescence in situ hybridization with a centromeric probe to identify the presence (MN+) or absence (MN-) of whole chromosomes within micronuclei, thereby determining the mechanism of arsenic-induced genotoxicity in vivo. We divided the study population into quintiles by urinary arsenic levels and found an exposure-dependent increase in micronucleated cell prevalence in quintiles 2-4 (urinary arsenic, 54-729 micrograms/liter). The largest increase appeared when quintile 4 was compared to quintile 1 [prevalence ratio, 3.0; 95% confidence interval (CI), 1.9-4.6]. The prevalence of MN+ increased to 3.1-fold in quintile 4 (95% CI, 1.4-6.6), and the prevalence of MN-increased to 7.5-fold in quintile 3 (95% CI, 2.8-20.3), suggesting that chromosome breakage was the major cause of MN formation. Prevalences of total MN, MN+, and MN- returned to baseline levels in quintile 5 (urinary arsenic, 729-1894 micrograms/liter), perhaps due to cytostasis or cytotoxicity. These results add additional weight to the hypothesis that ingesting arsenic-contaminated water enhances bladder cancer risk and suggest that arsenic induces genetic damage to bladder cells at drinking water levels close to the current United States Maximum Contaminant Level of 50 micrograms/liter for arsenic.
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PMID:Micronuclei in exfoliated bladder cells among individuals chronically exposed to arsenic in drinking water. 899 95

Deletion of all or part of chromosome 9 is a well-described genetic alteration in bladder tumors. It has been proposed that inactivation of a tumor-suppressor gene on chromosome 9 is an important event in tumor development. Recent reports have supported cyclin-dependent kinase inhibitor 2 (CDKN2, also known as MTS1, INK4, p16) at 9p21 as a candidate tumor-suppressor gene in solid tumors. However, the prevalence of CDKN2 mutations in primary bladder tumors has been controversial. Therefore, we applied gene-specific probes for CDKN2 and the interferon alpha gene (IFNA), also located at 9p21, to characterize further the genomic deletions at this locus in bladder cancer. Seventeen superficial (pTa or pT1) bladder tumor specimens were examined for gene deletion by fluorescence in situ hybridization. Dual-labeling hybridization with a repetitive pericentromeric probe for chromosome 9 and a gene-specific probe for CDKN2 was performed to characterize the gene copy number in relation to the chromosome 9 copy number on a cell-by-cell basis. Homozygous deletion for CDKN2 without homozygous IFNA deletion was found in 5 of 17 tumors tested. Both genes were deleted in one additional case, and one tumor showed deletion of IFNA without deletion of CDKN2. Homozygous deletion at the 9p21 locus was found only in tumors having monosomy for the chromosome 9 centromeric signal. These results indicate that the homozygous deletion of the CDKN2 gene is a frequent and early event in superficial bladder cancer.
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PMID:Frequent homozygous deletion of cyclin-dependent kinase inhibitor 2 (MTS1, p16) in superficial bladder cancer detected by fluorescence in situ hybridization. 917 98

The enzyme telomerase maintains a constant telomere length in immortalized cells, allowing unlimited cell proliferation. Almost all cancer cells express telomerase activity. However, little data is available regarding the role of telomerase activity in the detection of bladder cancer with a bladder wash specimen. We detected telomerase activity in a bladder wash specimen of bladder cancer and normal tissues, and compared them with final pathologic diagnosis. Twenty-three patients with transitional cell carcinoma (TCC) of the bladder were enrolled in our study. A bladder wash specimen was obtained before transurethral resection of the bladder (TURB) and normal and cancer tissues from the same patients during TURB. Telomerase activity was analyzed in each specimen a using telomeric repeat amplification protocol (TRAP) assay based on polymerase chain reaction (PCR) technique. Cytologic diagnosis was performed using Papanicolaou's stain with cytocentrifuged cytology preparation. We observed telomerase activity in 95.7% (22/23) of bath cancer tissues and bladder wash specimens; only one case did not express telomerase activity. Telomerase activity was undetected in all normal tissues except one, which was obtained from a patient with carcinoma in situ. A total of 69.6% (16/23) of wash specimens were positive in cytopathologic diagnosis. The accuracy of cytopathologic diagnosis in pathologic grade 2 or 3 was relatively high (83.3%, 15/18). However, in five cases of grade 1 TCC only 20% (1/5) of cytologic diagnosis was positive whereas the telomerase activity of wash specimens was detected in 80% (4/5). Our data demonstrates that not only the majority of human bladder cancer tissues, but also the bladder wash specimens obtained from patients with TCC, expressed telomerase activity. It indicates that telomerase activity may be a reliable marker in detecting bladder cancer especially in cases with a low grade that bladder wash cytology can miss.
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PMID:Telomerase activity: a potential marker of bladder transitional cell carcinoma in bladder washes. 925 15

A limited number of previous studies have indicated a low frequency of chromosome 10 allele losses and deletions in bladder cancers. We investigated the involvement of chromosome 10 in advanced bladder cancers. Loss of heterozygosity (LOH) was analysed in 19 microsatellite loci in 20 grade III invasive transitional cell carcinomas. Nine (45%) of the 20 tumors had at least one allele loss on the long arm of chromosome 10. The short arm of chromosome 10 was not affected. The most frequent LOH occurred at D10S215, where four (29%) of 14 of the informative cases had an allele loss. The minimal region with allele losses was located between the centromeric marker D10S1644 and the telomeric marker D10S541, which are separated by 2.52 cM. The results strongly suggest the existence within that region of a tumor suppressor gene or genes for advanced bladder cancer.
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PMID:Cluster of allele losses within a 2.5 cM region of chromosome 10 in high-grade invasive bladder cancer. 948 82


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