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研究生:林明鋒
研究生(外文):Ming-Fong Lin
論文名稱:尿路上皮細胞癌之上位遺傳表現
論文名稱(外文):Epigenetic Expression in Urothelial Cell Carcinoma
指導教授:陳全木陳全木引用關係
學位類別:碩士
校院名稱:國立中興大學
系所名稱:生命科學系所
學門:生命科學學門
學類:生物學類
論文種類:學術論文
畢業學年度:97
語文別:中文
論文頁數:69
中文關鍵詞:膀胱癌尿道腫瘤切除手術上位遺傳學甲基化生物晶片
外文關鍵詞:Bladder cancertransurethral resection of bladder tumor (TUR-BT)EpigeneticsCpG island microarray
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膀胱癌是泌尿系統第二常見的癌症,是所有泌尿系統腫瘤第二大死因,台灣地區平均每年死於泌尿道癌的患者中即有近半數是膀胱癌。在新診斷的膀胱癌病人當中,有百分之七十至八十屬於早期膀胱癌。雖然早期膀胱癌只要施以經尿道腫瘤切除手術就有不錯的治療效果,但仍有百分之三十五到七十的復發機率。依據目前的組織病理分類而言,仍無法完全預測大部分早期膀胱癌的復發及侵襲性。臨床上,偵測膀胱癌的復發可以利用膀胱鏡及尿液細胞學檢查,但是膀胱鏡屬在檢查時會非常不舒服或疼痛,且尿液細胞學檢查的敏感性不佳。依據近年來文獻的報告,某些基因與人類癌症侵襲、轉移及致病機轉可能有關。上位遺傳學,即基因上鹼基對的甲基化修飾或組蛋白修飾等,對於基因表現與否的調控機制上,扮演著一個重要角色。甲基化生物晶片是絕佳的大規模甲基化篩選平台。本研究利用此一篩選平台,針對膀胱癌細胞株與臨床膀胱癌腫瘤組織,進行基因片段之甲基化分析,發現約十七個甲基化基因在膀胱癌細胞株有明顯差異,這些差異基因以MS-PCR、COBRA、甲基化特異性核酸定序分析(bisulfite-sequencing)及免疫組織化學染色分析(IHC)的方法來進行驗證。針對TSP-1(ADAMTS19)基因的驗證,可證實TSP-1基因在尿路上皮細胞癌與膀胱癌腫瘤有高度甲基化的現象。
Bladder cancer is the second common cancer of genitor-urinary tract and is also the second cause of death of genitor-urinary tumor. More than half of the annual death of genitor-urinary malignancy in Taiwan is caused by bladder cancer. About 70 to 80 percent of newly diagnosed bladder cancer is early bladder cancer. Though early bladder cancer can be effectively treated by transurethral resection of bladder tumor (TUR-BT), the recurrence rate of these patients can be up to 35 to 70 percent. According to present histopathological classification, we still cannot predict the recurrent rate and progression rate of most early bladder cancer. Clinically, cystoscopy & urine cytology are standard method for follow-up. However, cystoscopy may cause pain and the sensitivity of urine cytology have made them limited ability during follow-up. Recent literatures had revealed that some genes might be related to pathogenesis, progression and metastasis of human malignant tumor. Epigenetics, including DNA methylation or histone modification of nucleotide, may play an important role in regulation of gene expression. High throughput analysis of CpG island microarray makes it to be a good tool for screening hypermethylation of genes. We used this high throughput tool to screen hypermethylated genes of urothelial cell carcinoma and found about 17 genes are hypermethylated. The methylated status of genes can be verify by MS-PCR, COBRA, bisulfite-sequencing and/or immunohistochemical stain. TSP-1(ADAMTS19) was verified to be hypermethylated .
目次
摘要(中文)…………………………………………………………………………….i
摘要(英文) ……………………………………………………………………………ii
目次………………………………………………………………………………….iii
表次……………………………………………………………………………………v
圖次…………………………………………………………………………………vi
壹、 緒言………………………………………………………………………………1
貳、 文獻探討…………………………………………………………………………2
一、膀胱癌……………………………………………………………………………2
(一)膀胱癌之流行病學與重要性………………………………………………2
(二)膀胱癌之發生原因…………………………………………………………2
二、上位遺傳學………………………………………………………………………5
(一)上位遺傳學於正常細胞扮演的角色………………………………………5
(二)上位遺傳學與腫瘤細胞的關係………………………………………… …7
(三)膀胱癌與上位遺傳學的關聯性…………………………………………10
三、本研究應用上位遺傳學研究方法的探討……………………………………12
(一)甲基化基因晶片之分析…………………………………………………12
(二)甲基特異性聚合酶連鎖反應(Methylation-specific PCR, MS-PCR) ……15
(三)重亞硫酸限制組合分析法 (combined bisulfite restriction analysis,
COBRA)……………………………………………..................................15
(四)甲基化特異性定序分析 (Sodium bisulfate sequencing)……………...…16
(五)免疫組織染色分析(immunohistochemical stain, IHC)…………………16
四、上位遺傳學於膀胱癌研究的動機與展望……………………………………..16
參、材料與方法………………………………………………………………………19
ㄧ、組織樣本與細胞株來源與保存…………………………………………..…… 19
(一) 膀胱腫瘤組織樣本來源與保存…………………………………………19
(二) 膀胱癌細胞株來源與保存………………………………………………19
二、差異性甲基化雜合晶片(Differentiation methylation hybridization,
DMH) …………………………………………………………………………19
(一) 樣本製備…………………………………………………………..….…19
1. 尿路上皮細胞株,SV-HUC-1及T24,DNA萃取…………………………19
2. 臨床膀胱腫瘤與相對應正常膀胱組織的DNA萃取……………………20
3. 樣本增幅產物(amplicon)製備………………………………………..….20
(二) 螢光標定與雜合反應……………………………………………………22
(三)螢光偵測與分析…………………………………………………………23
(四)尿路上皮細胞癌細胞株,T24,去甲基藥物(5-Aza-dC)處理……………23
(五)Expressed CpG Island Sequence Tag Microarray( ECIST) ………………23
三、甲基化基因群之驗證…………………………………………………………23
(一)甲基特異性聚合酶連鎖反應(Methylation-specific PCR, MS-PCR) ……23
1.膀胱腫瘤組織及尿路上皮細胞株之DNA萃取…………………………23
2. DNA之亞硫酸鈉化學修飾………………………………………………23
3. MS-PCR分析……………………………………………………………24
(二)重亞硫酸限制組合分析法 (combined bisulfite restriction analysis,
COBRA)…………………………………………………………………26
(三)甲基化特異性核酸定序分析(methylation-specific sequencing;
MS-sequencing)…………………………………………………………27
(四)免疫組織化學染色分析(Immuno-histo-chemical Stain, IHC) …………28
肆、結果與討論………………………………………………………………………29
ㄧ、 以差異性甲基化雜合晶片與ECIST分析尿路上皮細胞株的結果
(result of DMH & ECIST in urothelial cell line) ……………………………29
(一)差異性甲基化雜合晶片分析之再現性…………………………………29
(二)差異性甲基化雜合晶片(DMH)與ECIST之表現差異性 ………………34
(三)DMH 的螢光比值散佈圖(Scatter plots of DMH between urethelial
cell lines)與ECIST的基因篩檢…………………………………………34
(四)DMH 高度甲基化基因與 ECIST結果的分析…………………………34
二、MS-PCR 技術分析尿路上皮細胞株與臨床膀胱癌腫瘤組織樣本於P16及
TSP-1,即ADAMTS19, 兩個基因之甲基化狀態………………………………40
(一)p16於尿路上皮細胞株與臨床膀胱腫瘤檢體之甲基化剖繪分析圖……40
(二) TSP-1於尿路上皮細胞株與臨床膀胱腫瘤檢體之甲基化剖繪分析圖…40
三、COBRA技術分析尿路上皮細胞株與臨床膀胱癌腫瘤組織樣本於TSP-1
基因之甲基化狀態……………………………………………………………40
四、甲基化特異性核酸定序分析(bisulfite-sequencing)分析尿路上皮細胞株
與臨床膀胱癌腫瘤組織樣本於TSP-1基因之甲基化狀態…………………40
五、TSP-1蛋白抗體在臨床膀胱癌腫瘤組織之免疫組織化學染色分析(IHC) …45
六、尿路上皮細胞株DMH晶片與膀胱癌腫瘤DMH晶片的交集基因群………45
伍、結論………………………………………………………………………………48
陸、參考文獻…………………………………………………………………………49
柒、附表………………………………………………………………………………56
行政院衛生署編. (2005). 全民健康保險醫療統計年報. 臺北市,臺灣。行政院衛生署.
行政院衛生署編. (2006). 中華民國94年衛生統計系列. 死因統計. 臺北市,臺灣。 行政院衛生署.
Agathanggelou, A., W. N. Cooper, and F. Latif. (2005). Role of the Ras-association domain family 1 tumor suppressor gene in human cancers. Cancer Res. 65(9): 3497-3508.
Aharon, R. and A. D. Riggs (1980). "DNA methylation and gene function. Science 210(4470): 604-610.
Alberg, A. J., A. Kouzis, J. M. Genkinger, L. Gallicchio, A. E. Burke, S. C. Hoffman, M. Diener-West, K. J. Helzlsouer, and G. W. Comstock. (2007). A prospective cohort study of bladder cancer risk in relation to active cigarette smoking and household exposure to secondhand cigarette smoke. Am. J. Epidemiol. 165(6): 660-666.
Anand, P., A. Kunnumakara, C. Sundaram, K. Harikumar, S. Tharakan, O. Lai,B. Sung, and B. Aggarwal. (2008). Cancer is a preventable disease that requires major lifestyle changes. Pharm. Res. 25(9): 2097-2116.
Bestor, T. H. (2005). Transposons reanimated in mice. Cell 122(3): 322-325.
Bodey, B. (2002). Cancer-testis antigens: promising targets for antigen directed antineoplastic immunotherapy. Expert Opin. Biol. Th. 2(6): 577-584.
Cannon, J., C. A. Linke, and L.R. Cos. (1991). Cyclophosphamide-associated carcinoma of urothelium: modalities for prevention. Urology 38(5): 413-6.
Catto, J. W.F., A.-R. Azzouzi, I. Rehman, K. M. Feeley, S. S. Cross, N. Amira, G. Fromont, M. Sibony, O. Cussenot, M. Meuth, and F. C. Hamdy. (2005). Promoter hypermethylation is associated with tumor location, stage, and subsequent progression in transitional cell carcinoma. J. Clin. Oncol. 23(13): 2903-2910.
Chan, M. W. Y., L. W. Chan, N. L. S. Tang, J. H. M. Tong, K. W. Lo, T. L. Lee, H. Y. Cheung, W. S. Wong, P. S. F. Chan, F. M. M. Lai, and K. F. To. (2002). Hypermethylation of multiple genes in tumor tissues and voided urine in urinary bladder cancer patients. Clin. Cancer Res. 8(2): 464-470.
Chan, M. W.Y., L. W. Chan, N. L. S. Tang, K. W. Lo, J. H. M. Tong, A. W. H. Chan, H. Y. Cheung, W. S. Wong, P. S. F. Chan, F. M. M. Lai, and K. F. To. (2003). Frequent hypermethylation of promoter region of RASSF1A in tumor tissues and voided urine of urinary bladder cancer patients. Int. J. Cancer 104(5): 611-616.
Chang, L.-L., W.-T. Yeh, S-Y. Yang, W.-J. Wu, and C.-H. Huang. (2003). Genetic alterations of p16INK4a and p14ARF genes in human bladder cancer. J. urology 170(2): 595-600.
Chatterjee, S. J., B. George, P. J. Goebell, M. Alavi-Tafreshi, S. R. Shi, Y. K. Fung, P. A. Jones, C. Cordon-Cardo, R. H. Datar, and R. J. Cote, (2004). Hyperphosphorylation of pRb: a mechanism for RB tumour suppressor pathway inactivation in bladder cancer. J. Pathol. 203(3): 762-770.
Chen, J. J. W., K. Peck, T.-M. Hong, S.-C. Yang, Y.-P. Sher, J.-Y. Shih, R. Wu, J.-L. Cheng, S. R. Roffler, C.-W. Wu, and P.-C. Yang. (2001). Global analysis of gene expression in invasion by a lung cancer model. Cancer Res. 61(13): 5223-5230.
Chiang, H. S., H. R. Guo, C. L. Hong, S. M. Lin, and E. F. Lee. (1993). The incidence of bladder cancer in the black foot disease endemic area in Taiwan. Brit. J. Urol. 71(3): 274-8.
Chow, W. H., P. Lindblad, G. Gridley, O. Nyren, J. K. McLaughlin, M. S. Linet, G. A. Pennello, H. O. Adami, and F. J. F. Jr.. (1997). Risk of urinary tract cancers following kidney or ureter stones.[see comment]. J. Natl. Cancer I. 89(19): 1453-7.
Clark, S. J., J. Harrison, and P. L. Molloy. (1997). Sp1 binding is inhibited by mCpmCpG methylation. Gene 195(1): 67-71.
Clark, S. J., J. Harrison, C. L. Paul, and M. Frommer. (1994). High sensitivity mapping of methylated cytosines. Nucleic Acids Res. 22(15): 2990-7.
Cui, H., P. Onyango, S. Brandenburg, Y. Wu, C.-L. Hsieh, and A. P. Feinberg. (2002). Loss of imprinting in colorectal cancer linked to hypomethylation of H19 and IGF2. Cancer Res 62(22): 6442-6446.
Dulaimi, E., R. G. Uzzo, R. E. Greenberg, T. Al-Saleem, and P. Cairns. (2004). Detection of bladder cancer in urine by a tumor suppressor gene hypermethylation panel. Clin. Cancer Res. 10(6): 1887-1893.
Ehrlich, M. and R. Y. H. Wang (1981). 5-methylcytosine in eukaryotic DNA. Science 212(4501): 1350-1357.
Esteller, M. (2008). Epigenetics in cancer. New Engl. J. Med. 358: 1148-1159.
Feinberg, A. P. (1999). Imprinting of a genomic domain of 11p15 and loss of imprinting in cancer: An introduction. Cancer Res. 59(7 Suppl.): 1743s-1746.
Feinberg, A. P. and B. Vogelstein (1983). Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature 301(5895): 89-92.
Fraga, M. F., M. Herranz, J. Espada, E. Ballestar, M. F. Paz, S. Ropero, E. Erkek, O. Bozdogan, H. Peinado, A. Niveleau, J.-H. Mao, A. Balmain, A. Cano, and M. Esteller. (2004). A mouse skin multistage carcinogenesis model reflects the aberrant DNA methylation patterns of human tumors. Cancer Res. 64(16): 5527-5534.
Friedrich, M. G., D. J. Weisenberger, J. C. Cheng, S. Chandrasoma, K. D. Siegmund, M. L. Gonzalgo, M. I. Toma, H. Huland, C. Yoo, Y. C. Tsai, P. W. Nichols, B. H. Bochner, P. A. Jones, and G. Liang. (2004). Detection of methylated apoptosis-associated genes in urine sediments of bladder cancer patients. Clin. Cancer Res. 10(22): 7457-7465.
Frommer, M., L. E. McDonald, D. S. Millar, C. M. Collis, F. Watt, G. W. Grigg, P. L. Molloy, and C. L. Paul. (1992). A genomic sequencing protocol that yields a positive display of 5-methylcytosine residues in individual DNA strands. Proc. Natl. Acad. Sci. USA. 89(5): 1827-31.
Gary, O. and T. Dan (2003). The role of Ras superfamily proteins in bladder cancer progression. J. urology 170(5): 1987-1993.
Glas, A. S., D. Roos, M. Deutekom, A. H. Zwinderman, P. M. M. Bossuyt, and K. H. Kurth. (2003). Tumor markers in the diagnosis of primary bladder cancer. A systematic review. J. Urology 169(6): 1975-1982.
Golka, K., A. Wiese, G. Assennato, H. M. Bolt, K. Golka, A. Wiese, G. Assennato, and H. M. Bolt. (2004). Occupational exposure and urological cancer. World J. Urol. 21(6): 382-91.
Gonzalez-Zulueta, M., C. M. Bender, A. S. Yang, T. Nguyen, R. W. Beart, J. M. Van Tornout, and P. A. Jones. (1995). Methylation of the 5'' CpG island of the p16/CDKN2 tumor suppressor gene in normal and transformed human tissues correlates with gene silencing. Cancer Res. 55(20): 4531-4535.
Greger, V., E. Passarge, W. Hopping, E. Messmer, and B. Horsthemke. (1989). Epigenetic changes may contribute to the formation and spontaneous regression of retinoblastoma. Hum. Genet. 83(2): 155-8.
Groah, S. L., D. A. Weitzenkamp, D. P. Lammertse, G. G. Whiteneck, D. C. Lezotte, and R. F. Hamman. (2002). Excess risk of bladder cancer in spinal cord injury: Evidence for an association between indwelling catheter use and bladder cancer. Arch. Phys. Med. Rehab. 83(3): 346-351.
Hanahan, D. and J. Folkman. (1996). Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 86(3): 353-364.
Hartge, P., D. Silverman, R. Hoover, C. Schairer, R. Altman, D. Austin, K. Cantor, M. Child, C. Key, and L. D. Marrett. (1987). Changing cigarette habits and bladder cancer risk: a case-control study. J. Natl. Cancer I. 78(6): 1119-25.
Heney, N. M. (1992). Natural history of superficial bladder cancer. Prognostic features and long-term disease course. Urol. Clin. N. Am. 19: 429-433.
Herman, J. G., F. Latif, Y Weng, M. I. Lerman, B Zbar, S Liu, D Samid, D. S. Duan, J. R. Gnarra, and W. M. Linehan. (1994). Silencing of the VHL tumor-suppressor gene by DNA methylation in renal carcinoma. Proc. Natl. Acad. Sci. USA. 91(21): 9700-9704.
Herman, J. G., A. Merlo, L. Mao, R. G. Lapidus, J.-P. J. Issa, N. E. Davidson, D. Sidransky, and S. B. Baylin. (1995). Inactivation of the CDKN2/p16/MTS1 gene Is frequently associated with aberrant DNA methylation in all common human cancers. Cancer Res. 55(20): 4525-4530.
Herman, J. G., J. R. Graff, S. Myohanen, B. D. Nelkin, and S. B. Baylin. (1996). Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proc. Natl. Acad. Sci. USA. 93: 9821-9826.
Herman, J. G. and S. B. Baylin. (2003). Gene silencing in cancer in association with promoter hypermethylation. New Engl. J. Med. 349: 2042-2054.
Hicks, R. M. and J. Chowaniec. (1977). The importance of synergy between weak carcinogens in the induction of bladder cancer in experimental animals and humans. Cancer Res. 37(8 Pt 2): 2943-9.
Holliday, R. (1987). The inheritance of epigenetic defects. Science 238(4824): 163-170.
Holmang, S., H. Hedelin, C. Anderstrom, E. Holmberg, C. Busch and S. L. Johansson. (1999). Recurrence and progression in low grade papillary urothelial tumors. J Urol. 162: 702-707.
Hoover, R. N. and P. H. Strasser. (1980). Artificial sweeteners and human bladder cancer. Preliminary results. Lancet 1(8173): 837-40.
Howe, G., J. Burch, A. B. Miller, G.M. Cook, J Esteve, B Morrison, P Gordon, L. W. Chambers, G Fodor, and G. M. Winsor. (1980). Tobacco use, occupation, coffee, various nutrients, and bladder cancer. J. Natl. Cancer I. 64(4): 701 - 13.
Huang, T., M. Perry, and D. E. Laux. (1999). Methylation profiling of CpG islands in human breast cancer cells. Hum. Mol. Genet. 8(3): 459-470.
Huncharek, M. and B. Kupelnick. (2005). Personal use of hair dyes and the risk of bladder cancer: results of a meta-analysis. Public Health Rep. 120(1): 31-8.
Ioachim, E., M. C. Michael, M. Salmas, K. Damala, E. Tsanou, M. M. Michael, V. Malamou-Mitsi, and N. E. Stavropoulos. (2006). Thrombospondin-1 expression in urothelial carcinoma: prognostic significance and association with p53 alterations, tumour angiogenesis and extracellular matrix components. BMC Cancer 6: 140-147.
Jebar, A. H., C. D. Hurst, D.C. Tomlinson, C. Johnston, C. F. Taylor, and M. A. Knowles. (2005). FGFR3 and Ras gene mutations are mutually exclusive genetic events in urothelial cell carcinoma. Oncogene 24(33): 5218-5225.
Jones, P. A. and S. B. Baylin (2002). The fundamental role of epigenetic events in cancer. Nat. Rev. Genet. 3(6): 415-428.
Jones, P. A. and S. B. Baylin (2007). The epigenomics of cancer. Cell 128(4): 683-692.
Kaneda, A. and A. P. Feinberg (2005). Loss of imprinting of IGF2: A common epigenetic modifier of intestinal tumor risk. Cancer Res. 65(24): 11236-11240.
Kantor, A. F., P. Hartge, R. N. Hoover, A. S. Narayana, J. W. Sullivan, and F. J. F. Jr.. (1984). Urinary tract infection and risk of bladder cancer. Am. J. Epidemiol. 119(4): 510-5.
Kleinerman, R. A., J. D. Boice, Jr., H. H. Storm, P. Sparen, A. Andersen, E. Pukkala,
C. F. Lynch, B. F. Hankey, and J. T. Flannery. (1995). Second primary cancer after treatment for cervical cancer. An international cancer registries study. Cancer 76(3): 442-52.
Lamm, S. H., D. M. Byrd, M. B. Kruse, M. Feinleib, S. H. Lai, S. H. Lamm, D. M. Byrd, M. B. Kruse, M. Feinleib, and S.-H. Lai. (2003). Bladder cancer and arsenic exposure: differences in the two populations enrolled in a study in southwest Taiwan. Biomed. Environ. Sci. 16(4): 355-68.
Lamm, S. H., A. Engel, C. A. Penn, R. Chen, M. Feinleib, S. H. Lamm, A. Engel, C. A. Penn, R. Chen, and M. Feinleib. (2006). Arsenic cancer risk confounder in southwest Taiwan data set.[see comment]. Environ. Health Persp. 114(7): 1077-82.
Lee, M.-G., H.-Y. Kim, D.-S. Byun, S.-J. Lee, C.-H. Lee, J. I. Kim, S.-G. Chang, and S.-G. Chi. (2001). Frequent epigenetic inactivation of RASSF1A in human bladder carcinoma. Cancer Res. 61(18): 6688-6692.
Marsit, C. J., M. R. Karagas, H. Danaee, M. Liu, A. Andrew, A. Schned, H. H. Nelson, and K. T. Kelsey. (2006). Carcinogen exposure and gene promoter hypermethylation in bladder cancer. Carcinogenesis 27: 112-116.
Maruyama, R., S. Toyooka, K. O. Toyooka, K. Harada, A. K. Virmani, S. Zochbauer-Muller, A. J. Farinas, F. Vakar-Lopez, J. D. Minna, A. Sagalowsky, B. Czerniak, and A. F. Gazdar. (2001). Aberrant promoter methylation profile of bladder cancer and its relationship to clinicopathological features. Cancer Res. 61(24): 8659-8663.
Meyer, T. and I. R. Hart. (1998). Mechanisms of tumour metastasis. Eur. J. Cancer 34(2): 214-221.
Mitra, A. P., R. H. Datar, and R. J. Cote. (2005). Molecular staging of bladder cancer. BJU Int. 96(1): 7-12.
Miyao, N., Y. C. Tsai, S. P. Lerner, A. F. Olumi, C. H., III Spruck, M. Gonzalez-Zulueta, P. W. Nichols, D. G. Skinner, and P. A. Jones. (1993). Role of chromosome 9 in human bladder cancer. Cancer Res. 53(17): 4066-4070.
Morrison, A. S. and J. E. Buring. (1980). Artificial sweeteners and cancer of the lower urinary tract. New Engl. J. Med. 302(10): 537-41.
Mostafa, M. H., S. A. Sheweita, and P. J. O''Connor. (1999). Relationship between schistosomiasis and bladder cancer. Clin. Microbiol. Rev. 12(1): 97-111.
Ng, H. H. and A. Bird (2000). Histone deacetylases: silencers for hire. Trends. Biochem. Sci. 25(3): 121-6.
Pasin, E., D. Y. Josephson, A. P. Mitra, R. J. Cote, and J. P. Stein. (2008). Superficial bladder cancer: An update on etiology, molecular development, classification, and natural history. Rev. Urol. 10(1): 31-43.
Paulette, M.-F., R. T. Cheney, and J. Schwaller. (2006). Genetic alterations in urothelial bladder carcinoma. Cancer 106(6): 1205-1216.
Piper, J. M., J. Tonascia, and G. M. Matanoski. (1985). Heavy phenacetin use and bladder cancer in women aged 20 to 49 years. New Engl. J. Med. 313(5): 292-5.
Reik, W. and A. Lewis. (2005). Co-evolution of X-chromosome inactivation and imprinting in mammals. Nat. Rev. Genet. 6(5): 403-410.
Shi, H., P. S. Yan, C. M. Chen, F. Rahmatpanah, C. Lofton-Day, C. W. Caldwell, and T. H. Huang. (2002). Expressed CpG island sequence tag microarray for dual screening of DNA hypermethylation and gene silencing in cancer cells. Cancer Res. 62(11): 3214-20.
Smith, S. S., B. E. Kaplan, L. C. Sowers, and E. M. Newman. (1992). Mechanism of human methyl-directed DNA methyltransferase and the fidelity of cytosine methylation. Proc. Natl. Acad. Sci. USA. 89(10): 4744-4748.
Steeg, P. S., G. Bevilacqua, R. Pozzatti, L. A. Liotta, and M. E. Sobel. (1988). Altered expression of NM23, a gene associated with low tumor metastatic potential, during Adenovirus 2 Ela inhibition of experimental metastasis. Cancer Res. 48(22): 6550-6554.
Stein, J. P., G. D. Grossfeld, D. A. Ginsberg, D. Esrig, J. A. Freeman, A. J. Figueroa, D. G. Skinner, and R. J. Cote. (1998). Prognostic markers in bladder cancer: a contemporary review of the literature. J Urol. 160: 645-659.
Volm, T., P. Pfaff, R. Gnann, and R. Kreienberg. (2001). Bladder carcinoma associated with cyclophosphamide therapy for ovarian cancer occurring with a latency of 20 years. Gynecol. Oncol. 82(1): 197-9.
Weihrauch, M. R. and V. Diehl (2004). Artificial sweeteners--do they bear a carcinogenic risk? Ann. Oncol. 15(10): 1460-5.
Wu, X.-R. (2005). Urothelial tumorigenesis: a tale of divergent pathways. Nat. Rev. Cancer 5(9): 713-725.
Xiong, Z. and P. W. Laird (1997). COBRA: a sensitive and quantitative DNA methylation assay. Nucleic Acids Res. 25(12): 2532-4.
Yan, P. S., M. R. Perry, D. E. Laux, A. L. Asare, C. W. Caldwell, and T. H.-M. Huang. (2000). CpG Island Arrays: An application toward deciphering epigenetic signatures of breast cancer. Clin. Cancer Res. 6(4): 1432-1438.
Yates, D. R., I. Rehman, M. Meuth, S. S. Cross, F. C. Hamdy, and J. W. F. Catto. (2005). Methylational urinalysis: a prospective study of bladder cancer patients and age stratified benign controls. Oncogene 25(13): 1984-1988.
Yoneda, T. (1998). Cellular and molecular mechanisms of breast and prostate cancer metastasis to bone. Eur. J. Cancer 34(2): 240-245.
Zeegers, M. P., R. A. Goldbohm, P. A. van den Brandt, M. P. A. Zeegers, R. A. Goldbohm, and P. A. van den Brandt. (2002). A prospective study on active and environmental tobacco smoking and bladder cancer risk (The Netherlands). Cancer Causes Control 13(1): 83-90.
Zetter, P., Bruce R. (1998). Angiogenesis and tumor metastasis. Ann. Rev. Med. 49(1): 407-424.
Zhang, Y., Y. Xiong, and W. G. Yarbrough. (1998). ARF promotes MDM2 degradation and atabilizes p53: ARF-INK4a locus deletion impairs both the Rb and p53 tumor suppression pathways. Cell 92(6): 725-734.
Zieger, K., L. Dyrskjot, C. Wiuf, J. L. Jensen, C. L. Andersen, K. M.-E. Jensen, and T. F. Orntoft. (2005). Role of activating fibroblast growth factor receptor 3 mutations in the development of bladder tumors. Clin. Cancer Res.11: 7709-7719.
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