Mesane Kanseri Tanılı Olgularda p53 Geni Mutasyon Analizi
p53 geni, insan malignitelerinin yaklaşık %50’sinde mutasyona uğrayan bir tümör supresör gendir. p53 geni, mesane kanserinde en fazla mutasyona uğrayan tümör supresör geni olma özelliğini taşımaktadır. Bu yüzden mesane kanserinin prognozunun belirlenmesinde önemli bir biomarker olabilir. Bu araştırmada, mesane kanseri teşhisi konmuş 22 olguya ait mesane tümör doku örneklerinden DNA izole edilip, PCR metoduyla 5. ve 7. ekson bölgeleri amplifiye edildikten sonra, enzim kesimi yapılarak 5. ve 7. eksonlarda p53 geni mutasyon analizi gerçekleştirilmiştir. Mutasyon analizi gerçekleştirilen olguların %45’inde p53 geni mutasyonu saptanmış olup, saptanan mutasyonların %60’ının 5. eksonda bulunan 175. kodonda, %40’ının ise 7. eksonda bulunan 249. kodonda olduğu belirlenmiştir
Mesane Kanseri Tanılı Olgularda p53 Geni Mutasyon Analizi
___
- Levine AJ. p53, the cellular gatekeeper for growth and division. Cell, 1997; 88(3): 323-331.
- Hollstein M, Rice K, Greenblatt MS, et al. Database of p53 gene somatic mutations in human tumors and cell lines. Nucleic Acids Res, 1994; 22(17): 3551- 3555.
- DeWolf WC. p53: an important key to understanding urologic cancer. AUA Update Series, 1995; 15: 258.
- Smith ND, Rubenstein JN, Eggener SE, et al. The p53 Tumor Suppressor Gene and Nuclear Protein: Basic Science Review and Relevance in the Management of Bladder Cancer (Clinical Urology: Review Article). J Urol, 2003; 169(4): 1219-1228.
- Vet JA, Witjes JA, Marras SA, et al. Predictive value of p53 mutations analyzed in bladder washings for progression of high-risk superficial bladder cancer. Clin Cancer Res, 1996; 2(6): 1055-1061.
- Zlotta AR, Noel J-C, Fayt I, et al. Correlation and prognostic significance of p53, p21WAF1/CIP1 and Ki-67 expression in patients with superficial bladder tumors treated with bacillus Calmette-Guerin intravesical therapy. J Urol, 1999; 161(3): 792-798.
- Fleshner N, Kapusta L, Ezer D, Herschorn S, Klotz L. p53 nuclear accumulation is not associated with decreased disease-free survival in patients with node positive transitional cell carcinoma of the bladder. J Urol, 2000; 164(4): 1177-1182.
- Shiao YH, Rugge M, Correa P, Lehmann HP, Scheer WD. p53 alteration in gastric precancerous lesions. Am J Pathol, 1994; 144(3): 511-517.
- Moore LE, Smith AH, Eng C, et al. p53 alterations in bladder tumors from arsenic and tobacco exposed patients. Carcinogenesis, 2003; 24(11); 1785-1791.
- McCredie M, Stewart JH, Ford JM, et al. Phenacetin- containing analgesics and cancer of the bladder or renal pelvis in women. Br J Urol, 1983; 55(2): 220-224.
- Piper JM, Tonocia J, Matanoski GM. Heavy phenacetin use and bladder cancer in women aged 20 to 49 years. N Engl J Med, 1985; 313(5): 292-295.
- LaRue H, Allard P, Simoneau M, et al. p53 point mutations in initial superficial bladder cancer occur only in tumors from current or recent cigarette smokers. Carcinogenesis, 2000; 21(1): 101-106.
- Greenblatt MS, Bennett WP, Hollstein M, Harris CC. Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis (Review). Cancer Res,1994; 54(18): 4855-4878.
- Sidransky D, von Eschenbach A, Tsai YC, et al. Identification of p53 gene mutations in bladder cancers and urine samples. Science, 1991; 252(5006): 706-709.
- Yoshimura I, Kudoh J, Saito S, Tazaki H, Shimizu N. p53 gene mutation in recurrent superficial bladder cancer. J Urol, 1995; 153(5): 1711-1715.
- Taylor JA, Li Y, He M, et al. p53 mutations in bladder tumors from arylamine-exposed workers. Cancer Res, 1996; 56(2): 294-298.
- Xu X, Stower MJ, Reid IN, Garner RC, Burns PA. Molecular screening of multifocal transitional cell carcinoma of the bladder using p53 mutations as biomarkers. Clin Cancer Res, 1996; (10): 1795-1800.
- Lin HY, Huang CH, Wu WJ, Chou YH, Fan PL, Lung FW. Mutation of the p53 tumor suppressor gene in transitional cell carcinoma of the urinary tract in Taiwan. Kaohsiung J Med Sci, 2005; 21(2): 57-64.
- http://www.akdeniz.edu.tr/tip/web/ders_form/ UROLOJI/baykara_mesane.htm Erişim 20.06.2005
- Lorenzo Romero JG, Salinas Sanchez AS, Gimenez Bachs JM. p53 Gene mutations in superficial bladder cancer. Urol Int, 2004; 73(3): 212-218.
- Oyasu R, Nan L, Szumel RC, Kawamata H, Hirohashi S. p53 gene mutations in human urothelial carcinomas: analysis by immunohistochemistry and single-strand conformation polymorphism. Mod Pathol, 1995; 8(2): 170-176.
- Phillips H.A., Howard G.C., Miller W.R. p53 mutations as a marker of malignancy in bladder washing samples from patients with bladder cancer. Br J Cancer, 2000; 82(1): 136-41.
- Lorenzo Romero JG, Salinas-Sanchez AS, Gimenez- Bachs JM, et al. Prognostic implications of p53 gene mutations in bladder tumors. J Urol, 2003; 169(2): 492-499.