Allelic losses of chromosomes 9, 11, and 17 in bladder cancer (original) (raw)
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Allelic Losses of Chromosomes 9, 11, and 17 in Human Bladder Cancer
Cancer Research, 1990
Twenty-five human bladder tumors were examined for loss of hetero zygosity of markers on chromosomes 6p, 9q, lip, 14q, and 17p. These studies show that all of the markers were reduced to homozygosity in at least some of the tumors. They also confirmed earlier studies by Fearon et al. [Nature (Lond.), 318: 377-380, 1985| that approximately 40% of bladder tumors were reduced to homozygosity for markers on chromo some 11 p. I lowever, the greatest frequency of alleile loss was seen for chromosomes 9q (67% of informative cases) and 17p (63% of informative cases) with both chromosomes being lost concordanti}' in 10 out of 20 informative tumors. Allelic loss of chromosome 9q has not been previ ously observed with other human cancers; however, deletions of 17p have been reported in breast, lung, and colorectal carcinomas. The data raise the interesting possibility that allelic losses of specific chromosomes might be a feature of cancer in a particular differentiated cell type whereas loss of other chromosomes harboring more generally acting tumor sup pressor genes might be a common feature of human cancers.
Allelic Losses of Chromosomes 9, 11, and 17 in Human Bladder Cancer1
2000
Twenty-five human bladder tumors were examined for loss of hetero zygosity of markers on chromosomes 6p, 9q, lip, 14q, and 17p. These studies show that all of the markers were reduced to homozygosity in at least some of the tumors. They also confirmed earlier studies by Fearon et al. (Nature (Lond.), 318: 377-380, 1985| that approximately 40% of bladder tumors
Chromosome 9 allelic losses and microsatellite alterations in human bladder tumors
Cancer research, 1994
Chromosome 9 allelic losses have been reported as a frequent and early event occurring in bladder cancer. It has been postulated that a candidate tumor suppressor gene may reside on this chromosome, alterations of which may lead to the development of a subset of superficial bladder tumors. More recently, the involvement of two different regions harboring suppressor loci, one on each of both chromosome 9 arms, has been proposed. We undertook the present study with the objectives of better defining the deleted regions of chromosome 9 in bladder tumors, as well as evaluating the frequency of microsatellite alterations affecting certain loci on this chromosome in urothelial neoplasia. Seventy-three primary bladder tumors were analyzed using a set of highly polymorphic markers, and results were correlated with pathological parameters associated with poor clinical outcome. We observed that, overall, 77% of the tumors studied showed either loss of heterozygosity for one or more chromosome ...
International Journal of Cancer, 1998
The most frequent genetic aberration found in transitional cell carcinoma (TCC) of the bladder involves chromosome 9. Loss of heterozygosity (LOH) analyses show deletions of both chromosome 9p and 9q, while in situ hybridization studies suggest a significant percentage of tumours with monosomy 9. To investigate the types of chromosome 9 losses that occur in bladder cancer, we have studied 40 tumours with different techniques such as in situ hybridization (ISH), flow cytometry and LOH analysis. LOH for one or more markers was found in 43% of the tumours. This percentage does not differ from previous reports. With ISH, complete monosomy for chromosome 9 was observed in only 1 of the 40 tumours. Four other tumours had monosomic subpopulations, representing 23-40% of the cells. In 18 cases, an underrepresentation of the chromosome 9 centromere relative to chromosome 6 or to the ploidy of the tumour was observed, including the cases with monosomy. In 5 of these 18 cases, the relative loss could not be confirmed by LOH. In addition, when LOH and a relative underrepresentation were observed in the same tumour, the extent of LOH as measured by the intensity of allele loss, was often not related to the extent of underrepresentation. We therefore conclude that complete monosomy of chromosome 9 is rare in TCCs of the bladder and that a relative loss of centromere signal may not be related to a loss compatible with inactivation of a tumour suppressor gene. LOH was found in TCCs of all stages and grades. Our results suggest that loss of tumour suppressor genes on chromosome 9 is an early event in the pathogenesis of bladder cancer. Int.
Journal of the Egyptian National Cancer Institute, 2005
Loss of heterozygosity (LOH) in tumor samples is believed to be a marker for the absence of a functional tumor suppressor gene. Non-random chromosome deletion and LOH at specific chromosomal regions are identified in a number of common human cancers including carcinoma of the bladder, which is considered the most predominant cancer in Egypt due to the prevalence of schistosomiasis. The main objective of the present study is to clarify the role of chromosomes 8 and 9 in the establishment and/or progression of schistosomiasis-related bladder cancer through detection of LOH of 8 microsatellite markers on both chromosomes. It also aims to compare the LOH pattern of the tested markers between schistosomiasis- associated and non schistosomiasis-associated bladder cancer. To achieve this purpose, DNA was extracted from the tumor specimens and the corresponding peripheral blood samples of 42 primary bladder cancer patients (schistosomal and non schistosomal). Twenty nine of these were diagn...
Cancer research, 1996
The most common genetic alteration identified to date in bladder cancer is loss of heterozygosity (LOH) of chromosome 9, suggesting the presence of possible tumor suppressor genes on this chromosome. We attempted to map the location of these genes by analyzing 69 primary transitional cell carcinomas of the bladder with a panel of microsatellite markers for LOH on chromosome 9. Monosomy 9 (defined by LOH of all informative markers analyzed on 9p and 9q) was detected in 26 of 69 (38%) tumors, and 22 of 69 (32%) tumors showed subchromosomal deletions. Twelve tumors (17%) demonstrated partial LOH of chromosome 9 and indicated two distinct regions of LOH. Eight tumors showed distal allelic loss of 9q with a minimal region of common deletion flanked proximally by marker GSN on 9q33. Six tumors showed proximal allelic loss of 9p and 9q with a minimal area of common deletion flanked by markers D9S970 on 9p12 and D9S283 on 9q21. Two tumors showed loss of both the distal region of 9q and the ...
The American Journal of Pathology, 2002
Carcinoma in situ (CIS) of the urinary bladder is a flat, aggressive lesion and may be the most common precursor of invasive bladder cancer. Although chromosome 9 alterations are among the earliest and most prevalent genetic alterations in bladder cancer, discrepancy exists about the frequency of chromosome 9 losses in CIS. We analyzed 22 patients with CIS of the bladder (15 patients with isolated CIS, 7 patients combined with synchronous pTa or pT1 carcinomas) for gains and losses of chromosome (peri)centromere loci 1q12, 7p11-q11, 9p11-q12, and 9p21 harboring the INK4A/ARF locus (p16(INK4A)/p14(ARF)) and INK4B (p15(INK4B)) by multiple-target fluorescence in situ hybridization, and for p53 protein accumulation by immunohistochemistry. In 15 of 20 (75%) CIS lesions analyzed p53 overexpression was detected, whereas aneusomy for chromosomes 1 and 7 was identified in 20 of 22 (91%) CIS. In 13 of 22 (60%) CIS cases analyzed, 12 of which were not associated with a synchronous pTa or pT1 carcinoma, no numerical losses for chromosome 9 (p11-q12 and 9p21) were detected as compared with chromosomes 1 and 7. Furthermore 6 of 12 (50%) patients showed a metachronous invasive carcinoma within 2 years. In the remaining nine biopsies CIS lesions (40%) were recognized that showed losses of chromosome 9p11-q12 and 9p21, six of these were associated with a synchronous pTa or pT1 carcinoma. Three of these carcinomas were pTa and exhibited loss of 9q12 as well as a homozygous deletion of 9p21. The others were invasive carcinomas in which CIS lesions were also recognized that showed no numerical loss of chromosome 9, but did show an accumulation of p53. In conclusion our data demonstrate that predominantly isolated CIS lesions contained cells with no specific loss of chromosome 9, as opposed to CIS lesions with synchronous carcinomas that showed evidence of chromosome 9 loss. Furthermore our data strengthen the proposition that p53 mutations (p53 overexpression) precede loss of chromosomes 9 and 9p21 in CIS as precursor for invasive bladder cancer, as opposed to noninvasive carcinomas where chromosome 9 (9p11-q12) losses are early and frequently combined with homozygous deletions of 9p21.
British journal of cancer, 1999
The most frequent genetic alterations in transitional cell carcinoma (TCC) of the bladder involve loss of heterozygosity (LOH) on chromosome 9p and 9q. The LOH on chromosome 9p most likely targets the CDKN2 locus, which is inactivated in about 50% of TCCs. Candidate genes that are the target for LOH on chromosome 9q have yet to be identified. To narrow the localization of one or more putative tumour suppressor genes on this chromosome that play a role in TCC of the bladder, we examined 59 tumours with a panel of microsatellite markers along the chromosome. LOH was observed in 26 (44%) tumours. We present evidence for two different loci on the long arm of chromosome 9 where potential tumour suppressor genes are expected. These loci are delineated by interstitial deletions in two bladder tumours. Our results confirm the results of others and contribute to a further reduction of the size of these regions, which we called TCC1 and TCC2. These regions were examined for homozygous deletio...
The random development of LOH on chromosome 9q in superficial bladder cancers
The Journal of Pathology, 2002
Allelic loss on chromosome 9q is a very frequent event in bladder carcinogenesis. In recent years, efforts have been directed towards identifying the postulated tumour suppressor genes on this chromosome arm by deletion mapping and mutation analysis. However, no convincing candidate genes have been identified. This paper describes the development of chromosome 9q alterations in multiple recurrent superficial bladder cancers of ten patients and shows that loss of heterozygosity (LOH) on this chromosome is almost never the characteristic first step. The regions of loss are multiple and variable in different tumours from the same patient and expand in subsequent tumours. Moreover, the regions of loss vary from patient to patient. It is concluded that even if 9q harbours a bladder cancer gatekeeper gene, it is unlikely that the gene will be identified through LOH analysis alone.