Abstract
Approximately 2/3 of patients diagnosed with superficial transitional cell carcinoma of the urinary bladder (TCC) will recur within 2 years. Loss of chromosome 9 and loss of heterozygosity (LOH) at 9q34 in index TCCs identify a subset of patients at high risk of recurrence. This study explores genetic alterations on chromosomes 4, 8, 11 and 17 as predictors of recurrence. A total of 109 carcinomas were investigated at 26 loci. DNA was extracted from microdissected archival normal/tumour tissue and was analysed for loss of heterozygosity (LOH). Fluorescent PCR was performed and genotyping carried out on a Perkin Elmer ABI377 sequencer. LOH of D11S490 or D17S928 was significantly more frequent in index carcinomas of patients who experienced recurrence compared to those with no recurrence (P = 0.004 and 0.019 respectively). These results suggest that loss of these regions is associated with recurrence of TCC. Further investigation is required to identify genes in these regions, which might be responsible for driving recurrence in TCC of the urinary bladder. © 2001 Cancer Research Campaign
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References
Adshead JM, Kessling AM and Ogden CW (1998) Genetic initiation, progression and prognostic markers in transitional cell carcinoma of the bladder: A summary of the structural and transcriptional changes, and the role of developmental genes. Br J Urol 82: 503–512
Ambrosini G, Adida C and Altieri DC (1997) A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med 3: 917–921
Bartlett JMS, Watters AD, Ballantyne SA, Going JJ, Grigor KM and Cooke TG (1998) Is chromosome 9 loss a marker of disease recurrence in transitional cell carcinoma of the urinary bladder?. Br J Cancer 77: 2193–2198
Bell SM, Zuo J, Myers RM and Knowles MA (1996) Fluorescence in situ hybridisation deletion mapping at 4p16.3 in bladder cancer cell lines refines the localisation of the critical interval to 30 kb. Genes Chromosom Cancer 17: 108–117
Chaturvedi V, Li L, Hodges S, Johnston D, Ro JY, Logothetis C, Von Eschenbach AC, Batsakis JG and Czerniak B (1997) Superimposed histologic and genetic mapping of chromosome 17 alterations in human urinary bladder neoplasia. Oncogene 14: 2059–2070
Czermiak B, Chaturvedi V, Li L, Hodges S, Johnston D, Roy JY, Luthur A, Logothetis C, Von Eschenbach AC, Grossman HB, Benedict WF and Batsakis JG (1999) Superimposed histologic and genetic mapping of chromosome 9 in progression of human urinary bladder neoplasm: implications for a genetic model of multi step urothelial carcinogenesis and early detection of urinary bladder cancer. Oncogene 18: 1185–1196
Edwards J, Duncan P, Going JJ, Watters AD and Bartlett JMS (2000) Loss of hererozgosity on chromosome 9 as a potential marker of recurrence and progression in bladder cancer. Br J Cancer 83, (Suppl 1):76(abstract)
Esrig D, Freeman JA, Stein JP and Skinner DG (1997) Early cystectomy for clinical stage T1 transitional cell carcinoma of the bladder. Semin Urol Oncol 15: 154–160
Fearon ER, Feinberg AP, Hamilton SH and Vogelstein B (1985) Loss of genes on the short arm of chromosome 11 in bladder cancer. Nature 318: 377–380
Foulkes WD, Campbell IG, Stamp GWH and Trowsdale J (1993) Loss of heterozygosity and amplification on chromosome 11q in human ovarian cancer. Br J Cancer 67: 268–273
Godwin AK, Vanderveer L, Schultz DC, Lynch HT, Altomare DA, Buetow KH, Daly M, Getts LA, Mansy A and Rosenblum N (1994) A common region of deletion on chromosome 17q in both sporadic and familial epithelial ovarian tumours distal to BRCA1. Am J Hum Genet 55: 666–677
Going JJ and Lamb RF (1996) Practical histological microdissection for PCR analysis. J Pathol 179: 121–124
Hampton GM, Penny LA, Baergen RN, Larson A, Brewer C, Liao S, Busby-Earle RMC, Williams AWR, Steel CM, Bird CC, Stanbridge EJ and Evans GA (1994) Loss of heterozygosity in cervical carcinoma: Subchromosomal localisation of a putative tumour suppressor gene to chromosome 11q22-q24. Proc Natl Acad Sci USA 91: 6953–6957
Iizuka M, Sugiyama Y, Shiraishi M, Jones C and Sekiya T (1995) Allelic losses in human chromosome 11 in lung cancers. Genes Chromosom Cancer 13: 40–46
Jakob IJ, Smith SA, Wiseman RW, Futreal PA, Harrington T, Osborne RJ, Leech V, Molyneux A, Berchuck A and Ponder BAJ (1993) A deletion unit on chromosome 17q in epithelial ovarian tumours distal to the familial breast/ovarian cancer locus. Cancer Res 53: 1218–1221
Kalikin LM, Qu X, Frank TS, Caduff RF, Svoboda SM, Law DJ and Petty EM (1996) Detailed deletion analysis of sporadic breast carcinomas defines an interstitial region of allelic loss on 17q25. Genes Chromosom Cancer 17: 64–68
Kalikin LM, Frank TS, Svoboda-Newman SM, Wetzel JC, Cooney KA and Petty EM (1997) A region of interstitial 17q25 allelic loss in ovarian carcinomas coincides with a defined region of loss in breast carcinomas. Oncogene 14: 1991–1994
Knowles MA (1999) Identification of novel bladder tumour suppressor genes. Electrophoresis 20: 269–279
Knowles MA (1995) Molecular genetics of bladder cancer: Pathways of development and progression. Br J Urol 75, (Suppl 11):57–66
Li F, Ambrosinin G, Chu EY, Plescia J, Tognin S, Marchisio PC and Altieri DC (1998) Control of apoptosis and mitotic spindle checkpoint by survivin. Nature 396: 580–584
Locus Link www.ncbi.nlm.nih.gov/locuslink/list.cgi.
Lupher ML, Rao N, Lill NL, Andoniou CE, Miyake S, Clark EA and Druker BH (1998) Cbl-mediated negative regulation of the Syk tyrosine kinase. A critical role for Cbl phosphotyrosine-binding domain binding to Syk phosphotyrosine 323. J Biol Chem 273: 35273–35281
Monaco C, Negrini M, Sozzi G, Veronese ML, Vorechovsky I, Godwin AK and Croce CM (1997) Molecular cloning and characterisation of LOH11CR2A, a new gene within a refined minimal region of LOH at 11q23. Genomics 46: 217–222
Murakami Y, Nobukuni T, Tamura K, Maruyama T, Sekiya T, Arai Y, Gomyou H, Tanigami A, Ohki M, Cabin D, Frischmeyer P, Hunt P and Reeves RH (1998) Localisation of tumour suppressor activity important in nonsmall cell lung carcinoma on chromosome 11q. Proc Natl Acad Sci USA 95: 8153–8158
Niederacher D, Picard F, van Roeyen C, An H-X, Bender HG and Beckmann MW (1997) Patterns of allelic loss on chromosome 17 in sporadic breast carcinomas detected by fluroescent labelled microsatellite analysis. Genes Chromosom Cancer 18: 181–192
Nishiyama H, Hornigold NH, Davies AM and Knowles MA (1999) A sequence ready 840-kb PAC contig spanning the candidate tumour suppressor locus DBC1 on human chromosome 9q32-q33. Genomics 59: 335–338
Ohgaki K, Iinda A, Ogawa O, Kubota Y, Akimoto M and Emi M (1999) Localisation of tumour suppressor gene associated with distant metastasis of urinary bladder cancer to a 1-Mb interval on 8p22. Genes Chromosom Cancer 25: 1–5
O'Neill KL, McKelvey VJ, Hoper M, Monteverde H, Odlong-Smee GW, Logan H, Abram WP and McKenna PG (1992) Breast tumour thymidine kinase levels and disease recurrence. Med Lab Sci 49: 244–247
Petty EM, Miller DE, Grant AL, Collins EE, Glover TW and Law DJ (1996) FISH localisation of the soluble thymidine kinase gene (TK1) to human 17q25, a region of chromosomal loss in sporadic breast tumours. Cytogenet Cell Genet 72: 319–321
Petty EM, Kalikin LM, Orringer MB and Beer DG (1998) Distal chromosome 17q loss in Barretts esophageal adenocarcinomas and gastric cardia adenocarcinomas: implication for tumourgenesis. Mol Carc 22: 222–228
Plummer SJ, Adams L, Simmons JA and Casey G (1997) Localisation of a growth suppressor activity in MCF7 breast cancer cells to chromosome 17q24–25. Oncogene 14: 2339–2345
Richter J, Jiang F, Gorog JP, Sartonius G, Egerter C, Gasser TC, Moch H, Mihatsch MJ and Sauter G (1997) Marked genetic differences between stage pTa and stage pT1 papillary bladder cancer detected by comparative genomic hybridisation. Cancer Res 57: 2860–2864
Sauter G, Carroll P, Moch H, Kailioniemi A, Kerschmann R, Narayan P, Mihatsch MJ and Waldman FM (1995) c-myc copy number gains in bladder cancer detected by fluorescence in situ hybridisation. Am J Pathol 146: 1131–1139
Sidransky D, Von Eschenbach A, Tsai YC, Jones P, Summerhayes I, Marshall F, Paul M, Green P, Hamilton SR, Frost P and Vogelstein B (1991) Identification of p53 gene mutations in bladder cancers and urine samples. Science 252: 706–709
Simon R, Burger H, Brinkschmidt C, Bocker W, Hertle L and Terpe HJ (1998) Chromosomal aberrations associated with invasion in papillary superficial bladder cancer. J Pathol 185: 345–351
Shaw ME and Knowles MA (1995) Deletion mapping of chromosome 11 in carcinoma of the bladder. Genes Chromosom Cancer 13: 1–8
Spruck CH, Ohneseit PF, Gonzalez-Sulueta M, Esrig D, Noriomi M, Tsai YC, Lerner SP, Schmutte A, Yang AS, Cote R, Dubeau LD, Nichols PW, Hermann GG, Steven K, Horn T, Skinner DG and Jones PA (1994) Two molecular pathways to transitional cell carcinoma of the bladder. Cancer Res 54: 784–788
Theile M, Hartman S, Scherthan H, Arnold W, Deppert W, Frege R, Glaab RF, Haensch W and Scherneck S (1995) Suppression of tumorigenicity of breast cancer cells by transfer of chromosome 17 does not require transferred BRCA1 and p53 genes. Oncogene 10: 439–447
Tsutsumi M, Sugano K, Yamaguchi K, Kakizoe T and Akaza H (1997) Correlation of allelic loss of the P53 gene and tumour grade, stage, and malignant progression in bladder cancer. Int J Urol 4: 74–78
Van der Meijden APM (1999) Bladder cancer. BMJ 317: 1366–1369
Voorter CE, Ummelen MI, Ramaekers FS and Hopman AH (1996) Loss of chromosome 11 and 11p/q imbalances in bladder cancer detected by fluorescence in situ hybridisation. Int J Cancer 65: 301–307
Wagner U, Bubendorf L, Gasser TC, Moch H, Gorog JP, Richter J, Mihatsch MJ, Waldman FM and Sauter G (1997) Chromosome 8p deletions are associated with invasive tumour growth in urinary bladder cancer. Am J Pathol 151: 753–759
Wagner U, Suess K, Luginbuhl T, Schmid U, Ackermann D, Zellweger T, Maurer R, Alund G, Knonagel H, Rist M, Jordan P, Moch H, Mihatsch MJ, Gasser TC and Sauter G (1999) Cyclin D1 overexpression lacks prognostic significance in superficial urinary bladder cancer. J Pathol 188: 44–50
Watters AD, Ballantyne SA, Going JJ, Grigor KM and Bartlett JMS (2000) Aneusomy of chromosomes 7 and 17 predicts the recurrence of transitional cell carcinoma of the urinary bladder. Br J Urol 85: 42–47
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Edwards, J., Duncan, P., Going, J. et al. Loss of heterozygosity on chromosomes 11 and 17 are markers of recurrence in TCC of the bladder. Br J Cancer 85, 1894–1899 (2001). https://doi.org/10.1054/bjoc.2001.2159
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DOI: https://doi.org/10.1054/bjoc.2001.2159
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