Urologia Internationalis
Original Paper
Genetic Aberrations of NAT2 and Chromosome 8: Their Association with Progression in Transitional Cell Carcinoma of the Urinary BladderWatters A.D.a · Stacey M.W.d · Going J.J.b · Grigor K.M.c · Cooke T.G.a · Sim E.d · Bartlett J.M.S.aDepartments of aSurgery and bPathology, Glasgow Royal Infirmary, University of Glasgow, cDepartment of Pathology, University of Edinburgh, and dDepartment of Pharmacology, University of Oxford, UK
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Article / Publication Details
Published online: October 05, 2001
Issue release date: October 2001
Number of Print Pages: 5
Number of Figures: 0
Number of Tables: 3
ISSN: 0042-1138 (Print)
eISSN: 1423-0399 (Online)
For additional information: https://www.karger.com/UIN
Abstract
Introduction/Objective: N-acetyltransferase 2 (NAT2), mapped to 8p22, is a polymorphic enzyme which metabolizes aromatic amines. Loss of heterozygosity of 8p22 is associated with an increased risk of bladder cancer. This study evaluated NAT2 and chromosome 8 in sequential tumours from bladder cancer patients to determine if NAT2 alterations increase the risk of progression. Materials and Methods: Thirty-seven sequential carcinomas from 19 patients were assessed using fluorescence in situ hybridization. Results: Five carcinomas showed loss of NAT2; 4 of these were from pTa/pT1 tumours. Polysomy 8 was observed in 4 of 14 (29%) primary carcinomas (pTa/pT1), in 4 of 12 (33%) pTa/pT1 recurrences, and in 90% (9/10) of the detrusor muscle invasive tumours (pT2+). 6 of 8 (75%) locally invasive tumours with polysomy 8 were from patients who subsequently developed disease progression (pT2+). In total, 13.5% (5/37) of the carcinomas were abnormal for NAT2, and 46% (17/37) were abnormal for chromosome 8 copy number. Polysomy 8 was associated with high grade (p = 0.01) and stage (p = 0.03) and disease progression (p = 0.03). Conclusion: Whilst there does not appear to be an association between loss of NAT2 and risk of progression in transitional cell carcinoma, the high rate of polysomy of chromosome 8 implies that other genes on this chromosome significantly influence disease progression.
© 2001 S. Karger AG, Basel
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References
-
Office of Population Censuses and Studies DH1, Cancer Statistics. London, HMSO, 1969–1987.
-
Office of Population Censuses and Studies MB1, Cancer Statistics. London, HMSO, 1971–1984.
- van der Meijden PAM: Bladder cancer – clinical review. BMJ 1998;317:1366–1369.
- Hickman D, Risch A, Buckle V, Spurr N, Jeremiah S, McCarthy A, Sim E: Chromosomal localization of human genes for arylamine N-acetyltransferase. Biochem J 1994;297:441–445.
- Matas N, Thygesen P, Stacey M, Risch A, Sim E: Mapping AAC1, AAC2 and AACP, the genes for arylamine N-acetyltransferase, carcinogen metabolising enzymes on human chromosome 8p22, a region frequently deleted in tumours. Cytogenet Cell Genet 1997;77:290–295.
- Knowles MA, Shaw ME, Proctor AJ: Deletion mapping of chromosome 8 in cancers of the urinary bladder using restriction fragment length polymorphisms and microsatellite polymorphisms. Oncogene 1993;8:1357–1364.
- Wagner U, Bubendorf L, Gasser TC, Moch H, Görög JP, Richter J, Mihatsch HJ, Waldman FM, Sauter G: Chromosome 8p deletions are associated with invasive tumor growth in urinary bladder cancer. Am J Pathol 1997;151:753–759.
- Dalbagni G, Presti J, Reuter V, Fair WR, Cordon-Cardo C: Genetic alterations in bladder cancer. Lancet 1993;342:469–471.
- Reznikoff CA, Belair CD, Yeager TR, Savelieva E, Blelloch RH, Puthenveettil JA, Cuthill S: A molecular genetic model of human bladder cancer pathogenesis. Semin Oncol 1996;23:571–584.
- Knowles MA: The genetics of transitional cell carcinoma: Progress and potential clinical application. BJU Int 1999;84:412–427.
- Pycha A, Mian C, Haitel A, Hofbauer J, Wiener H, Marberger M: Fluorescence in situ hybridization identifies more aggressive types of primarily noninvasive (stage pTa) bladder cancer. J Urol 1997;157:2116–2119.
- Bartlett JM, Watters AD, Ballantyne SA, Going JJ, Grigor KM, Cooke TG: Is chromosome 9 loss a marker of disease recurrence in transitional cell carcinoma of the urinary bladder? Br J Cancer 1998;77:2193–2198.
- Bartlett JM, Adie L, Watters AD, Going JJ, Grigor KM: Chromosomal aberrations in transitional cell carcinoma that are predictive of disease outcome are independent of polyploidy. BJU Int 1999;84:775–779.
-
Watters AD, Ballantyne SA, Going JJ, Grigor KM, Bartlett JM: Aneusomy of chromosomes 7 and 17 predicts the recurrence of transitional cell carcinoma of the urinary bladder. BJU Int 2000;85:42–47.
External Resources
- Stacey M, Matas N, Drake M, Payton M, Fakis G, Greenland J, Sim E: Arylamine N-acetyltransferase type 2 (NAT2), chromosome 8 aneuploidy, and identification of a novel NAT1 cosmid clone: An investigation in bladder cancer by interphase FISH. Genes Chromosomes Cancer 1999;25:376–383.
-
Case RAM, Hosker ME, McDonald DB, Pearson JT: Tumours of the urinary bladder in workmen engaged in the manufacture and use of certain dyestuff intermediates in the British chemical industry. 1. The role of aniline, benzidine alpha-naphthylamine and beta-naphthylamine. Br J Ind Med 1954;11:75–103.
-
Cartwright RA, Glashan RW, Rogers HJ, Ahmad RA, Barham-Hall D, Higgins E, Kahn MA: Role of N-acetyltransferase phenotypes in bladder carcinogenesis: A pharmacogenetic epidemiological approach to bladder cancer. Lancet 1982;ii:842–846.
- Risch A, Wallace DM, Bathers S, Sim E: Slow N-acetylation genotype is a susceptibility factor in occupational and smoking related bladder cancer. Hum Mol Genet 1995;4:231–236.
- Ohgaki K, Iida A, Ogawa O, Kubota Y, Akimoto M, Emi M: Localization of tumor suppressor gene associated with distant metastasis of urinary bladder cancer to a 1-Mb interval on 8p22. Genes Chromosomes Cancer 1999;25: 1–5.
- Thygesen P, Risch A, Stacey M, Fakis G, Takle L, Knowles M, Sim E: Genes for arylamine N-acetyltransferase in relation to loss of the short arm of chromosome 8 in bladder cancer. Pharmacogenetics 1999;9:1–8.
- Sato K, Qian J, Slezak JM, Lieber MM, Bostwick DG, Bergstralh EJ, Jenkins RB: Clinical significance of alterations of chromosome 8 in high-grade, advanced, nonmetastatic prostate carcinoma. J Natl Cancer Inst 1999;91:1574–1580.
- Christoph F, Schmidt B, Schmitz-Dräger BJ, Schulz WA: Over-expression and amplification of the c-myc gene in human urothelial carcinoma. Int J Cancer 1999;84:169–173.
- Eydmann ME, Knowles MA: Mutation analysis of 8p genes POLB and PPP2CB in bladder cancer. Cancer Genet Cytogenet 1997;93:167–171.
- Sauter G, Carroll P, Moch H, Kallioniemi A, Kerschmann R, Narayan P, Mihatsch MJ, Waldman FM: C-myc copy number gains in bladder cancer detected by fluorescence in situ hybridization. Am J Pathol 1995;146:1131–1139.
Article / Publication Details
Published online: October 05, 2001
Issue release date: October 2001
Number of Print Pages: 5
Number of Figures: 0
Number of Tables: 3
ISSN: 0042-1138 (Print)
eISSN: 1423-0399 (Online)
For additional information: https://www.karger.com/UIN
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