Hypermethylation in bladder cancer: Biological pathways and translational applications

Tumor Biology

Volumn 33, Issue 2, 2012, Pages 347-361

  Sánchez Carbayo, Marta ^a  

^a Centro Nacional de Investigaciones Oncológicas   (Spain)

Author keywords

Bladder cancer; Methylation

Indexed keywords

BCG VACCINE; CISPLATIN; DNA METHYLTRANSFERASE; TUMOR MARKER;

APOPTOSIS; ARTICLE; BLADDER CANCER; BLADDER CARCINOGENESIS; CANCER CELL; CANCER DIAGNOSIS; CANCER GROWTH; CANCER INVASION; CANCER PROGNOSIS; CELL CYCLE PROGRESSION; CPG ISLAND; DNA METHYLATION; DNA REPAIR; EARLY DIAGNOSIS; EPIGENETICS; GENE EXPRESSION PROFILING; GENE MUTATION; GENE SILENCING; GENETIC ANALYSIS; GENOME ANALYSIS; HISTOPATHOLOGY; HUMAN; PHARMACOGENETICS; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN FAMILY; SIGNAL TRANSDUCTION; TRANSCRIPTION REGULATION; TRANSLATION REGULATION; TRANSLATIONAL RESEARCH; TUMOR GENE; TUMOR SUPPRESSOR GENE; BIOLOGICAL MODEL; BLADDER TUMOR; DISEASE COURSE; GENETIC EPIGENESIS; GENETICS; METABOLISM; NEOPLASM; TUMOR CELL LINE;

APOPTOSIS; CELL LINE, TUMOR; CPG ISLANDS; DISEASE PROGRESSION; DNA METHYLATION; DNA REPAIR; EPIGENESIS, GENETIC; GENE SILENCING; HUMANS; MODELS, GENETIC; NEOPLASM INVASIVENESS; NEOPLASMS; TUMOR MARKERS, BIOLOGICAL; URINARY BLADDER NEOPLASMS;

EID: 84860265126     PISSN: 10104283     EISSN: 14230380     Source Type: Journal    
DOI: 10.1007/s13277-011-0310-2     Document Type: Article

References (145)

1. Jones PA, Laird PW. Cancer epigenetics comes of age. Nat Genet. 1999;21:163-7.
2. Bird A. DNA methylation patterns and epigenetic memory. Genes Dev. 2002;16:6-21.
3. Laird PW. The power and the promise of DNA methylation markers. Nat Rev Cancer. 2003;3:253-66.
4. Eden A, Gaudet F, Waghmare A, Jaenisch R. Chromosomal instability and tumors promoted by DNA hypomethylation. Science. 2003;300:455.
5. Wang Y, Leung FC. An evaluation of new criteria for CpG islands in the human genome as gene markers. Bioinformatics. 2004;20:1170-7.
6. Feinberg AP. Cancer epigenetics is no Mickey Mouse. Cancer Cell. 2005;8:267-8.
7. Esteller M. Cancer epigenomics: DNA methylomes and histonemodification maps. Nat Rev Gene. 2007;8:286-98.
8. Jones PA, Baylin SB. The epigenomics of cancer. Cell. 2007;128:683-92.
9. Esteller M. Epigenetic gene silencing in cancer: the DNA hypermethylome. Hum Mol Genet. 2007;16:50-9.
10. Suzuki MM, Bird A. DNA methylation landscapes: provocative insights from epigenomics. Nat Rev Genet. 2008;9:465-76.
11. Meissner A, Mikkelsen TS, Gu H, Wernig M, Hanna J, Sivachenko A, et al. Genome-scale DNA methylation maps of pluripotent and differentiated cells. Nature. 2008;454:766-70.
12. Esteller M. Epigenetics in cancer. N Engl J Med. 2008;358:1148-59.
13. Lister R, Pelizzola M, Dowen RH, Hawkins RD, Hon G, Tonti- Filippini J, et al. Human DNA methylomes at base resolution show widespread epigenomic differences. Nature. 2009;462:315-22.
14. Straussman R, Nejman D, Roberts D, Steinfeld I, Blum B, Benvenisty N, et al. Developmental programming of CpG island methylation profiles in the human genome. Nat Struct Mol Biol. 2009;16:564-71.
15. Lister R, Pelizzola M, Dowen RH, Hawkins RD, Hon G, Tonti- Filippini J, et al. Human DNA methylomes at base resolution show widespread epigenomic differences. Nature. 2009;462:315-22.
16. Kuroda A, Rauch TA, Todorov I, Ku HT, Al-Abdullah IH, Kandeel F, et al. Insulin gene expression is regulated by DNA methylation. PLoS One. 2009;4:e6953.
17. Thomson JP, Skene PJ, Selfridge J, Clouaire T, Guy J, Webb S, et al. CpG islands influence chromatin structure via the CpGbinding protein Cfp1. Nature. 2010;464:1082-6.
18. Irizarry RA, Ladd-Acosta C,Wen B,Wu Z, Montano C, Onyango P, et al. The human colon cancer methylome shows similar hypoand hypermethylation at conserved tissue-specific CpG island shores. Nat Genet. 2009;41:178-86.
19. Doi A, Park IH, Wen B, Murakami P, Aryee MJ, Irizarry R, et al. Differential methylation of tissue- and cancer-specific CpG island shores distinguishes human induced pluripotent stem cells, embryonic stem cells and fibroblasts. Nat Genet. 2009;41:1350-3.
20. Hellman A, Chess A. Gene body-specific methylation on the active X chromosome. Science. 2007;315:1141-3.
21. Futscher BW, Oshiro MM, Wozniak RJ, Holtan N, Hanigan CL, Duan H, et al. Role for DNA methylation in the control of cell type specific maspin expression. Nat Genet. 2002;31:175-9.
22. Hattori N, Nishino K, Ko YG, Hattori N, Ohgane J, Tanaka S, et al. Epigenetic control of mouse Oct-4 gene expression in embryonic stem cells and trophoblast stem cells. J Biol Chem. 2004;279:17063-9.
23. Tahiliani M, Koh KP, Shen Y, Pastor WA, Bandukwala H, Brudno Y, et al. Conversion of 5-methylcytosine to 5- hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science. 2009;324:930-5.
24. Ito S, D'Alessio AC, Taranova OV, Hong K, Sowers LC, Zhang Y. Role of Tet proteins in 5mC to 5hmC conversion, ES-cell selfrenewal and inner cell mass specification. Nature. 2010;466:1129-33.
25. Robertson KD, Uzvolgyi E, Liang G, Talmadge C, Sumegi J, Gonzales FA, et al. The human DNA methyltransferases (DNMTs) 1, 3a and 3b: coordinate mRNA expression in normal tissues and overexpression in tumors. Nucleic Acids Res. 1999;27:2291-8.
26. Robert MF, Morin S, Beaulieu N, Gauthier F, Chute IC, Barsalou A, et al. DNMT1 is required to maintain CpG methylation and aberrant gene silencing in human cancer cells. Nat Genet. 2003;33:61-5.
27. Robertson KD, Keyomarsi K, Gonzales FA, Velicescu M, Jones PA. Differential mRNA expression of the human DNA methyltransferases (DNMTs) 1, 3a and 3b during the G(0)/G(1) to S phase transition in normal and tumor cells. Nucleic Acids Res. 2000;28:2108-13.
28. Velicescu M, Weisenberger DJ, Gonzales FA, Tsai YC, Nguyen CT, Jones PA. Cell division is required for de novo methylation of CpG islands in bladder cancer cells. Cancer Res. 2002;62:2378-84.
29. Nakagawa T, Kanai Y, Saito Y, Kitamura T, Kakizoe T, Hirohashi S. Increased DNA methyltransferase 1 protein expression in human transitional cell carcinoma of the bladder. J Urol. 2003;170:2463-6.
30. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global Cancer Statistics CA. Cancer J Clin. 2011;61:69-90.
31. Sánchez-Carbayo M. Use of high-throughput DNA microarrays to identify biomarkers for bladder cancer. Clin Chem. 2003;49:23-31.
32. Sánchez-Carbayo M, Cordon-Cardó C. Molecular alterations associated with bladder cancer progression. Semin Oncol. 2007;34:75-84.
33. Sánchez-Carbayo M, Cordon-Cardo C. Applications of array technology: identification of molecular targets in bladder cancer. Br J Cancer. 2003;89:2172-7.
34. Wolff EM, Liang G, Jones PA. Mechanisms of disease: genetic and epigenetic alterations that drive bladder cancer. Nat Clin Pract Urol. 2005;2:502-10.
35. Gonzalgo ML, Datar RH, Schoenberg MP, Cote RJ. The role of deoxyribonucleic acid methylation in development, diagnosis, and prognosis of bladder cancer. Urol Oncol. 2007;25:228-35.
36. Henrique R, Costa VL, Jerónimo C. Methylation-based biomarkers for early detection of urological cancer. Crit Rev Oncog. 2007;13:265-82.
37. Enokida H, Nakagawa M. Epigenetics in bladder cancer. Int J Clin Oncol. 2008;13:298-307.
38. Kim YK, Kim WJ. Epigenetic markers as promising prognosticators for bladder cancer. Int J Urol. 2009;16:17-22.
39. Kim WJ, Kim YJ. Epigenetic biomarkers in urothelial bladder cancer. Expert Rev Mol Diagn. 2009;9:259-69.
40. Phé V, Cussenot O, Rouprêt M. Interest of methylated genes as biomarkers in urothelial cell carcinomas of the urinary tract. BJU Int. 2009;104:896-901.
41. Ley TJ, Ding L, Walter MJ, McLellan MD, Lamprecht T, Larson DE, et al. DNMT3A Mutations in acute myeloid leukemia. N Engl J Med. 2010;363:2424-2333.
42. Delhommeau F, Dupont S, Della Valle V, James C, Trannoy S, Massé A, et al. Mutation in TET2 in myeloid cancers. N Engl J Med. 2009;360:2289-301.
43. Bailey VJ, Easwaran H, Zhang Y, Griffiths E, Belinsky SA, Herman JG, et al. MS-qFRET: a quantum dot-based method for analysis of DNA methylation. Genome Res. 2009;19:1455-61.
44. Li M, Chen WD, Papadopoulos N, Goodman SN, Bjerregaard NC, Laurberg S, et al. Sensitive digital quantification of DNA methylation in clinical samples. Nat Biotechnol. 2009;27:858-63.
45. Malentacchi F, Forni G, Vinci S, Orlando C. Quantitative evaluation of DNA methylation by optimization of a differential-high resolution melt analysis protocol. Nucleic Acids Res. 2009;37: e86.
46. Marsit CJ, Karagas MR, Danaee H, Liu M, Andrew A, Schned A, et al. Carcinogen exposure and gene promoter hypermethylation in bladder cancer. Carcinogenesis. 2006;27:112-6.
47. Aleman A, Adrien L, Lopez-Serra L, Cordon-Cardo C, Esteller M, Belbin TJ, et al. Identification of DNA hypermethylation of SOX9 in association with bladder cancer progression using CpG microarrays. Br J Cancer. 2008;98:466-73.
48. Wilhelm-Benartzi CS, Koestler DC, Houseman EA, Christensen BC, Wiencke JK, Schned AR, et al. DNA methylation profiles delineate etiologic heterogeneity and clinically important subgroups of bladder cancer. Carcinogenesis. 2010;31:1972-6.
49. Wolff EM, Chihara Y, Pan F, Weisenberger DJ, Siegmund KD, Sugano K, et al. Unique DNA methylation patterns distinguish noninvasive and invasive urothelial cancers and establish an epigenetic field defect in premalignant tissue. Cancer Res. 2010;70:8169-78.
50. Nishiyama N, Arai E, Chihara Y, Fujimoto H, Hosoda F, Shibata T, et al. Genome-wide DNA methylation profiles in urothelial carcinomas and urothelia at the precancerous stage. Cancer Sci. 2010;101:231-40.
51. Marsit CJ, Houseman EA, Christensen BC, Gagne L, Wrensch MR, Nelson HH, et al. Identification of methylated genes associated with aggressive bladder cancer. PLoS One. 2010;5:e12334.
52. Marsit CJ, Koestler DC, Christensen BC, Karagas MR, Houseman EA, Kelsey KT. DNA methylation array analysis identifies profiles of blood-derived DNA methylation associated with bladder cancer. J Clin Oncol. 2011;29:1133-9.
53. Wilhelm-Benartzi CS, Christensen BC, Koestler DC, Andres Houseman E, Schned AR, Karagas MR, et al. Association of secondhand smoke exposures with DNA methylation in bladder carcinomas. Cancer Causes Control. 2011;22:1205-13.
54. Reinert T, Modin C, Castano FM, Lamy P, Wojdacz TK, Hansen LL, et al. Comprehensive genome methylation analysis in bladder cancer: identification and validation of novel methylated genes and application of these as urinary tumor markers. Clin Cancer Res. 2011;17:5582-92.
55. Fernandez AF, Assenov Y, Martin-Subero JI, Balint B, Siebert R, Taniguchi H, et al. A DNA methylation fingerprint of 1628 human samples. Genome Res. 2011. doi:10.1101/gr.119867.110.
56. Vallot C, Stransky N, Bernard-Pierrot I, Hérault A, Zucman-Rossi J, Chapeaublanc E, et al. A novel epigenetic phenotype associated with the most aggressive pathway of bladder tumor progression. J Natl Cancer Inst. 2011;103:47-60.
57. Serizawa RR, Ralfkiaer U, Dahl C, Lam GW, Hansen AB, Steven K, et al. Custom-designed MLPA using multiple short synthetic probes: application to methylation analysis of five promoter CpG islands in tumor and urine specimens from patients with bladder cancer. J Mol Diagn. 2010;12:402-8.
58. Cabello MJ, Grau L, Franco N, Orenes E, Alvarez M, Blanca A, et al. Multiplexed methylation profiles of tumor suppressor genes in bladder cancer. J Mol Diagn. 2011;13:29-40.
59. Agundez M, Grau L, Palou J, Algaba F, Villavicencio H, Sanchez-Carbayo M. Evaluation of the methylation status of tumour suppressor genes for predicting bacillus Calmette- Guérin response in patients with T1G3 high-risk bladder tumours. Eur Urol. 2011;60:131-40.
60. Zuiverloon TC, Beukers W, van der Keur KA, Munoz JR, Bangma CH, Lingsma HF, Eijkemans MJ, Schouten JP, Zwarthoff EC. A methylation assay for the detection of non-muscleinvasive bladder cancer (NMIBC) recurrences in voided urine. BJU Int 2011
61. Merlo A, Herman JG, Mao L, Lee DJ, Gabrielson E, Burger PC, et al. 5' CpG island methylation is associated with transcriptional silencing of the tumour suppressor p16/CDKN2/MTS1 in human cancers. Nature Med. 1995;1:686-92.
62. Herman JG, Graff JR, Myöhönen S, Nelkin BD, Baylin SB. Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci USA. 1996;93:9821-6.
63. Lukas J, Parry D, Aagaard L, Mann DJ, Bartkova J, Strauss M, et al. Retinoblastoma-protein-dependent cell-cycle inhibition by the tumor suppressor p16. Nature. 1995;375:503-6.
64. Weinberg RA. The retinoblastoma protein and cell cycle control. Cell. 1995;81:323-30.
65. Florl AR, Franke KH, Niederacher D, Gerharz CD, Seifert HH, Schulz WA. DNA methylation and the mechanisms of CDKN2A inactivation in transitional cell carcinoma of the urinary bladder. Lab Invest. 2000;80:1513-22.
66. Valenzuela MT, Galisteo R, Zuluaga A, Villalobos M, Nú̃ez MI, Oliver FJ, et al. Assessing the use of p16 (INK4a) promoter gene methylation in serum for detection of bladder cancer. Eur Urol. 2002;42:622-8. discussion 628-30.
67. Chan MW, Chan LW, Tang NL, Tong JH, Lo KW, Lee TL, et al. Hypermethylation of multiple genes in tumor tissues and voided urine in urinary bladder cancer patients. Clin Cancer Res. 2002;8:464-70.
68. Tada Y, Wada M, Taguchi K, Mochida Y, Kinugawa N, Tsuneyoshi M, et al. The association of death-associated protein kinase hypermethylation with early recurrence in superficial bladder cancers. Cancer Res. 2002;62:4048-53.
69. Chang LL, Yeh WT, Yang SY, Wu WJ, Huang CH. Genetic alterations of p16INK4a and p14ARF genes in human bladder cancer. J Urol. 2003;170:595-600.
70. Dominguez G, Silva J, Garcia JM, Silva JM, Rodriguez R, Mũoz C, et al. Prevalence of aberrant methylation of p14ARF over p16INK4a in some human primary tumors. Mutat Res. 2003;530:9-17.
71. Dulaimi E, Uzzo RG, Greenberg RE, Al-Saleem T, Cairns P. Detection of bladder cancer in urine by a tumor suppressor gene hypermethylation panel. Clin Cancer Res. 2004;10:1887-93.
72. Catto JW, Azzouzi AR, Rehman I, Feeley KM, Cross SS, Amira N, et al. Promoter hypermethylation is associated with tumor location, stage, and subsequent progression in transitional cell carcinoma. J Clin Oncol. 2005;23:2903-10.
73. Dhawan D, Hamdy FC, Rehman I, Patterson J, Cross SS, Feeley KM, et al. Evidence for the early onset of aberrant promoter methylation in urothelial carcinoma. J Pathol. 2006;209:336-43.
74. Friedrich MG, Weisenberger DJ, Cheng JC, Chandrasoma S, Siegmund KD, Gonzalgo ML, et al. Detection of methylated apoptosis-associated genes in urine sediments of bladder cancer patients. Clin Cancer Res. 2004;10:7457-65.
75. Kawamoto K, Enokida H, Gotanda T, Kubo H, Nishiyama K, Kawahara M, et al. p16INK4a and p14ARF methylation as a potential biomarker for human bladder cancer. Biochem Biophys Res Commun. 2006;339:790-6.
76. Jarmalaite S, Jankevicius F, Kurgonaite K, Suziedelis K, Mutanen P, Husgafvel-Pursiainen K. Promoter hypermethylation in tumour suppressor genes shows association with stage, grade and invasiveness of bladder cancer. Oncology. 2008;75:145-51.
77. Khin SS, Kitazawa R, Win N, Aye TT, Mori K, Kondo T, et al. BAMBI gene is epigenetically silenced in subset of high-grade bladder cancer. Int J Cancer. 2009;125:328-38.
78. Jarmalaite S, Andrekute R, Scesnaite A, Suziedelis K, Husgafvel- Pursiainen K, Jankevicius F. Promoter hypermethylation in tumour suppressor genes and response to interleukin-2 treatment in bladder cancer: a pilot study. J Cancer Res Clin Oncol. 2010;136:847-54.
79. Lin HH, Ke HL, Huang SP, Wu WJ, Chen YK, Chang LL. Increase sensitivity in detecting superficial, low grade bladder cancer by combination analysis of hypermethylation of Ecadherin, p16, p14, RASSF1A genes in urine. Urol Oncol. 2010;28:597-602.
80. Lin HH, Ke HL, Wu WJ, Lee YH, Chang LL. Hypermethylation of E-cadherin, p16,p14, and RASSF1A genes in pathologically normal urothelium predict bladder recurrence of bladder cancer after transurethral resection. Urol Oncol 2010.
81. Schlott T, Quentin T, Korabiowska M, Budd B, Kunze E. Alteration of the MDM2-p73-P14ARF pathway related to tumour progression during urinary bladder carcinogenesis. Int J Mol Med. 2004;14:825-36.
82. Yurakh AO, Ramos D, Calabuig-Farĩas S, López-Guerrero JA, Rubio J, Solsona E, et al. Molecular and immunohistochemical analysis of the prognostic value of cell-cycle regulators in urothelial neoplasms of the bladder. Eur Urol. 2006;50:506-15.
83. Pu RT, Laitala LE, Clark DP. Methylation profiling of urothelial carcinoma in bladder biopsy and urine. Acta Cytol. 2006;50:499-506.
84. Hoque MO, Begum S, Topaloglu O, Chatterjee A, Rosenbaum E, Van Criekinge W, et al. Quantitation of promoter methylation of multiple genes in urine DNA and bladder cancer detection. J Natl Cancer Inst. 2006;98:996-1004.
85. Yates DR, Rehman I, Meuth M, Cross SS, Hamdy FC, Catto JW. Methylational urinalysis: a prospective study of bladder cancer patients and age stratified benign controls. Oncogene. 2006;25:1984-8.
86. Yates DR, Rehman I, Abbod MF, Meuth M, Cross SS, Linkens DA, et al. Promoter hypermethylation identifies progression risk in bladder cancer. Clin Cancer Res. 2007;13:2046-53.
87. Brait M, Begum S, Carvalho AL, Dasgupta S, Vettore AL, Czerniak B, et al. Aberrant promoter methylation of multiple genes during pathogenesis of bladder cancer. Cancer Epidemiol Biomarkers Prev. 2008;17:2786-94.
88. Hoffmann MJ, Florl AR, Seifert HH, Schulz WA. Multiple mechanisms down regulate CDKN1C in human bladder cancer. Int J Cancer. 2005;114:406-13.
89. Chapman EJ, Harnden P, Chambers P, Johnston C, Knowles MA. Comprehensive analysis of CDKN2A status in microdissected urothelial cell carcinoma reveals potential haploinsufficiency, a high frequency of homozygous co-deletion and associations with clinical phenotype. Clin Cancer Res. 2005;11:5740-7.
90. Salem CE, Markl ID, Bender CM, Gonzales FA, Jones PA, Liang G. PAX6 methylation and ectopic expression in human tumor cells. Int J Cancer. 2000;87:179-85.
91. Hellwinkel OJ, Kedia M, Isbarn H, Budäus L, Friedrich MG. Methylation of the TPEF- and PAX6-promoters is increased in early bladder cancer and in normal mucosa adjacent to pTa tumours. BJU Int. 2008;101:753-7.
92. Scolnick DM, Halazonetis TD. Chfr defines a mitotic stress checkpoint that delays entry into metaphase. Nature. 2000;406:430-5.
93. Maruyama R, Toyooka S, Toyooka Ko, Harada K, Virmani AK, Zochbauer-Muller S, et al. Aberrant promoter methylation profile of bladder cancer and its relationship to clinicopathological features. Cancer Res. 2001;61:8659-63.
94. Cohen O, Inbal B, Kissil JL, Raveh T, Berissi H, Spivak- Kroizaman T, et al. DAP-kinase participates in TNF-a and Fasinduced apoptosis and its function requires the death domain. J Cell Biol. 1999;146:141-8.
95. Friedrich MG, Chandrasoma S, Siegmund KD, Weisenberger DJ, Cheng JC, Toma MI, et al. Prognostic relevance of methylation markers in patients with non-muscle invasive bladder carcinoma. Eur J Cancer. 2005;41:2769-78.
96. Christoph F, Kempkensteffen C,Weikert S, Köllermann J, Krause H, Miller K, et al. Methylation of tumour suppressor genes APAF-1 and DAPK-1 and in vitro effects of demethylating agents in bladder and kidney cancer. Br J Cancer. 2006;95:1701-7.
97. Christoph F, Weikert S, Kempkensteffen C, Krause H, Schostak M, Miller K, et al. Regularly methylated novel pro-apoptotic genes associated with recurrence in transitional cell carcinoma of the bladder. Int J Cancer. 2006;119:1396-402.
98. Chen WT, Hung WC, Kang WY, Huang YC, Chai CY. Urothelial carcinomas arising in arsenic-contaminated areas are associated with hypermethylation of the gene promoter of the death-associated protein kinase. Histopathology. 2007;51:785-92.
99. Christoph F, Hinz S, Weikert S, Kempkensteffen C, Schostak M, Miller K, et al. Comparative promoter methylation analysis of p53 target genes in urogenital cancers. Urol Int. 2008;80:398-404.
100. Wolff EM, Liang G, Cortez CC, Tsai YC, Castelao JE, Cortessis VK, et al. RUNX3 methylation reveals that bladder tumors are older in patients with a history of smoking. Cancer Res. 2008;68:6208-14.
101. Vinci S, Giannarini G, Selli C, Kuncova J, Villari D, Valent F, et al. Quantitative methylation analysis of BCL2, hTERT, and DAPK promoters in urine sediment for the detection of nonmuscle- invasive urothelial carcinoma of the bladder: a prospective, two-center validation study. Urol Oncol. 2011;29:150-6.
102. Shivapurkar N, Toyooka S, Toyooka KO, Reddy J, Miyajima K, Suzuki M, et al. Aberrant methylation of trail decoy receptor genes is frequent in multiple tumor types. Int J Cancer. 2004;109:786-9.
103. Khokhlatchev A, Rabizadeh S, Xavier R, Nedwidek M, Chen T, Zhang XF, et al. Identification of a novel Ras-regulated proapoptotic pathway. Curr Biol. 2002;12:253-65.
104. Lee MG, Kim HY, Byun DS, Lee SJ, Lee CH, Kim JI, et al. Frequent epigenetic inactivation of RASSF1A in human bladder carcinoma. Cancer Res. 2001;61:6688-92.
105. Negraes PD, Favaro FP, Camargo JL, Oliveira ML, Goldberg J, Rainho CA, et al. DNA methylation patterns in bladder cancer and washing cell sediments: a perspective for tumor recurrence detection. BMC Cancer. 2008;8:238.
106. Takeichi M. Cadherin cell adhesion receptors as a morphogenetic regulator. Science. 1991;251:1451-5.
107. Chambers AF, Matrisian LM. Changing views of the role of matrix metalloproteinases in metastasis. J Natl Cancer Inst. 1997;89:1260-70.
108. Hoque MO, Begum S, Brait M, Jeronimo C, Zahurak M, Ostrow KL, et al. Tissue inhibitor of metalloproteinases-3 promoter methylation is an independent prognostic factor for bladder cancer. J Urol. 2008;179:743-7.
109. Colognato H, Yurchenco PD. Form and function: the laminin family of heterotrimers. Dev Dyn. 2000;218:213-34.
110. Sathyanarayana UG, Maruyama R, Padar A, Suzuki M, Bondaruk J, Sagalowsky A, et al. Molecular detection of noninvasive and invasive bladder tumor tissues and exfoliated cells by aberrant promoter methylation of laminin-5 encoding genes. Cancer Res. 2004;64:1425-30.
111. Bornman DM, Mathew S, Alsruhe J, Herman JG, Gabrielson E. Methylation of the E-cadherin gene in bladder neoplasia and in normal urothelial epithelium from elderly individuals. Am J Pathol. 2001;159:831-5.
112. Ribeiro-Filho LA, Franks J, Sasaki M, Shiina H, Li LC, Nojima D, et al. CpG hypermethylation of promoter region and inactivation of E-cadherin gene in human bladder cancer. Mol Carcinog. 2002;34:187-98.
113. Horikawa Y, Sugano K, Shigyo M, Yamamoto H, Nakazono M, Fujimoto H, et al. Hypermethylation of an E-cadherin (CDH1) promoter region in high grade transitional cell carcinoma of the bladder comprising carcinoma in situ. J Urol. 2003;169:1541-5.
114. Owen HC, Giedl J, Wild PJ, Fine SW, Humphrey PA, Dehner LP, et al. Low frequency of epigenetic events in urothelial tumors in young patients. J Urol. 2010;184:459-63.
115. Chen PC, Tsai MH, Yip SK, Jou YC, Ng CF, Chen Y, et al. Distinct DNA methylation epigenotypes in bladder cancer from different Chinese sub-populations and its implication in cancer detection using voided urine. BMC Med Genomics. 2011;4:45.
116. Dumache R, David D, Kaycsa A, Minciu R, Negru S, Puiu M. Genetic and epigenetic biomarkers for early detection, therapeutic effectiveness and relapse monitoring in bladder cancer. Rev Med Chir Soc Med Nat Iasi. 2011;115:163-7.
117. Mori K, Enokida H, Kagara I, Kawakami K, Chiyomaru T, Tatarano S, et al. CpG hypermethylation of collagen type I alpha 2 contributes to proliferation and migration activity of human bladder cancer. Int J Oncol. 2009;34:1593-602.
118. Toki K, Enokida H, Kawakami K, Chiyomaru T, Tatarano S, Yoshino H, et al. CpG hypermethylation of cellular retinolbinding protein 1 contributes to cell proliferation and migration in bladder cancer. Int J Oncol. 2010;37:1379-88.
119. Costa VL, Henrique R, Danielsen SA, Duarte-Pereira S, Eknaes M, Skotheim RI, et al. Three epigenetic biomarkers, GDF15, TMEFF2, and VIM, accurately predict bladder cancer from DNA-based analyses of urine samples. Clin Cancer Res. 2010;16:5842-51.
120. Xuan Y, Kim S, Lin Z. Protein expression and gene promoter hypermethylation of CD99 in transitional cell carcinoma of urinary bladder. J Cancer Res Clin Oncol. 2011;137:49-54.
121. Ruppen I, Grau L, Orenes-Pĩero E, Ashman K, Gil M, Algaba F, et al. Differential protein expression profiling by iTRAQ-twodimensional LC-MS/MS of human bladder cancer EJ138 cells transfected with the metastasis suppressor KiSS-1 gene. Mol Cell Proteomics. 2010;10:2276-91.
122. Cebrian V, Fierro M, Orenes-Pĩero E, Grau L, Moya P, Ecke T, et al. KISS1 methylation and expression as tumor stratification biomarkers and clinical outcome prognosticators for bladder cancer patients. Am J Pathol. 2011;179:540-6.
123. Marsit CJ, Karagas MR, Andrew A, Liu M, Danaee H, Schned AR, et al. Epigenetic inactivation of SFRP genes and TP53 alteration act jointly as markers of invasive bladder cancer. Cancer Res. 2005;65:7081-5.
124. Urakami S, Shiina H, Enokida H, Kawakami T, Kawamoto K, Hirata H, et al. Combination analysis of hypermethylated Wntantagonist family genes as a novel epigenetic biomarker panel for bladder cancer detection. Clin Cancer Res. 2006;12:2109-16.
125. Urakami S, Shiina H, Enokida H, Kawakami T, Tokizane T, Ogishima T, et al. Epigenetic inactivation of Wnt inhibitory factor-1 plays an important role in bladder cancer through aberrant canonical Wnt/beta-catenin signaling pathway. Clin Cancer Res. 2006;12:383-91.
126. Sun J, Chen Z, Zhu T, Yu J, Ma K, Zhang H, et al. Hypermethylated SFRP1, but none of other nine genes "informative" for western countries, is valuable for bladder cancer detection in Mainland China. J Cancer Res Clin Oncol. 2009;135:1717-27.
127. Costa VL, Henrique R, Ribeiro FR, Carvalho JR, Oliveira J, Lobo F, et al. Epigenetic regulation of Wnt signaling pathway in urological cancer. Epigenetics. 2010;4:343-5.
128. Habuchi T, Takahashi T, Kakinuma H, Wang L, Tsuchiya N, Satoh S, et al. Hypermethylation at 9q32-33 tumour suppressor region is age-related in normal urothelium and an early and frequent alteration in bladder cancer. Oncogene. 2001;20:531-7.
129. Kim WJ, Kim EJ, Jeong P, Quan C, Kim J, Li QL, et al. RUNX3 inactivation by point mutations and aberrant DNA methylation in bladder tumors. Cancer Res. 2005;65:9347-54.
130. Kunze E, Wendt M, Schlott T. Promoter hypermethylation of the 14-3-3 sigma, SYK and CAGE-1 genes is related to the various phenotypes of urinary bladder carcinomas and associated with progression of transitional cell carcinomas. Int J Mol Med. 2006;18:547-57.
131. Yu J, Zhu T, Wang Z, Zhang H, Qian Z, Xu H, et al. A novel set of DNA methylation markers in urine sediments for sensitive-specific detection of bladder cancer. Clin Cancer Res. 2007;13:7296-304.
132. Kim EJ, Kim YJ, Jeong P, Ha YS, Bae SC, Kim WJ. Methylation of the RUNX3 promoter as a potential prognostic marker for bladder tumor. J Urol. 2008;180:1141-5.
133. Sanchez-Carbayo M, Schwarz K, Charytonowicz E, Cordon- Cardo C, Mundel P. Tumor suppressor role for myopodin in bladder cancer: loss of nuclear expression of myopodin is cellcycle dependent and predicts clinical outcome. Oncogene. 2003;22:5298-305.
134. Cebrian V, Alvarez M, Aleman A, Palou J, Bellmunt J, Gonzalez- Peramato P, et al. Discovery of myopodin methylation in bladder cancer. J Pathol. 2008;216:111-9.
135. Alvarez-Mugica M, Cebrian V, Fernandez-Gomez JM, Fresno F, Escaf S, Sanchez-Carbayo M. Myopodin methylation is associated with clinical outcome in patients with T1G3 bladder cancer. J Urol. 2010;4:1507-13.
136. Dokun OY, Florl AR, Seifert HH, Wolff I, Schulz WA. Relationship of SNCG, S100A4, S100A9 and LCN2 gene expression and DNA methylation in bladder cancer. Int J Cancer. 2008;123:2798-807.
137. Aleman A, Cebrian V, AlvarezM, Lopez V, Orenes E, Lopez-Serra L, et al. Identification of PMF1 methylation in association with bladder cancer progression. Clin Cancer Res. 2008;14:8236-43.
138. Kunze E, Schlott T. High frequency of promoter methylation of the 14-3-3 sigma and CAGE-1 genes, but lack of hypermethylation of the caveolin-1 gene, in primary adenocarcinomas and signet ring cell carcinomas of the urinary bladder. Int J Mol Med. 2007;20:557-63.
139. Eissa S, Swellam M, El-Khouly IM, Kassim SK, Shehata H, Mansour A, et al. Aberrant methylation of RAR{beta}2 and APC genes in voided urine as molecular markers for early detection of bilharzial and nonbilharzial bladder cancer. Cancer Epidemiol Biomarkers Prev. 2011;20:1657-64.
140. Serizawa RR, Ralfkiaer U, Steven K, Lam GW, Schmiedel S, Schüz J, et al. Integrated genetic and epigenetic analysis of bladder cancer reveals an additive diagnostic value of FGFR3 mutations and hypermethylation events. Int J Cancer. 2011;129:78-87.
141. Abbosh PH, Wang M, Eble JN, Lopez-Beltran A, Maclennan GT, Montironi R, et al. Hypermethylation of tumor-suppressor gene CpG islands in small-cell carcinoma of the urinary bladder. Mod Pathol. 2008;21:355-62.
142. Rouprêt M, Hupertan V, Yates DR, Comperat E, Catto JW, Meuth M, et al. A comparison of the performance of microsatellite and methylation urine analysis for predicting the recurrence of urothelial cell carcinoma, and definition of a set of markers by Bayesian network analysis. BJU Int. 2008;101:1448-53.
143. Renard I, Joniau S, van Cleynenbreugel B, Collette C, Naômé C, Vlassenbroeck I, et al. Identification and validation of the methylated TWIST1 and NID2 genes through real-time methylationspecific polymerase chain reaction assays for the noninvasive detection of primary bladder cancer in urine samples. Eur Urol. 2010;58:96-104.
144. Nishiyama N, Arai E, Nagashio R, Fujimoto H, Hosoda F, Shibata T, et al. Copy number alterations in urothelial carcinomas: their clinicopathological significance and correlation with DNA methylation alterations. 'Carcinogenesis. 2011;32:462-9.
145. ChungW, Bondaruk J, Jelinek J, Lotan Y, Liang S, Czerniak B, et al. Detection of bladder cancer using novel DNA methylation biomarkers in urine sediments. Cancer Epidemiol Biomarkers Prev. 2011;20:1483-91.