Epigenetics of kidney cancer and bladder cancer

Epigenomics

Volumn 3, Issue 1, 2011, Pages 19-34

  Hoffman, Amanda M ^a   Cairns, Paul ^a  

^a FOX CHASE CANCER CENTER   (United States)

Author keywords

bladder cancer; methylome; promoter hypermethylation; RCC; renal cell carcinoma; translational application; tumor suppressor gene

Indexed keywords

5 AZA 2' DEOXYCYTIDINE; AZACITIDINE; BEVACIZUMAB; CISPLATIN; CYCLIN DEPENDENT KINASE INHIBITOR 2A; DEATH ASSOCIATED PROTEIN KINASE; DNA; INTERLEUKIN 2; KALININ; MG 98; MICRORNA; RAS ASSOCIATION DOMAIN FAMILY PROTEIN 1A; SECRETED FRIZZLED RELATED PROTEIN 1; SECRETED FRIZZLED RELATED PROTEIN 2; SECRETED FRIZZLED RELATED PROTEIN 4; SECRETED FRIZZLED RELATED PROTEIN 5; TISSUE INHIBITOR OF METALLOPROTEINASE 3; UVOMORULIN; VORINOSTAT; WNT PROTEIN;

BLADDER CANCER; CANCER CELL; CANCER DIAGNOSIS; CANCER MORTALITY; CANCER PATIENT; CANCER RECURRENCE; CANCER SUSCEPTIBILITY; CHROMOSOME 16P; CHROMOSOME 3P; CHROMOSOME DELETION; COMPARATIVE GENOMIC HYBRIDIZATION; COWDEN SYNDROME; CPG ISLAND; DNA METHYLATION; DNA REPAIR; DRUG MEGADOSE; DRUG SAFETY; EPIGENETICS; EXTRACELLULAR MATRIX; GENE EXPRESSION; GENE IDENTIFICATION; GENE LOCATION; GENETIC PREDISPOSITION; HISTONE MODIFICATION; HUMAN; KIDNEY CANCER; KIDNEY CARCINOMA; LOSS OF FUNCTION MUTATION; LOW DRUG DOSE; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; PROGNOSIS; PROMOTER REGION; RECURRENCE RISK; REVIEW; RNA INTERFERENCE; RNA TRANSLATION; SIGNAL TRANSDUCTION; SOMATIC MUTATION; TUMOR GENE; TUMOR SUPPRESSOR GENE; UPREGULATION;

DNA METHYLATION; EPIGENESIS, GENETIC; GENES, TUMOR SUPPRESSOR; HISTONES; HUMANS; KIDNEY NEOPLASMS; MICRORNAS; MODELS, BIOLOGICAL; URINARY BLADDER NEOPLASMS;

EID: 79951923157     PISSN: 17501911     EISSN: 1750192X     Source Type: Journal    
DOI: 10.2217/epi.10.64     Document Type: Review

References (145)

1. Jemal A, Siegel R, Xu J, Ward E: Cancer statistics, 2010. CA Cancer J. Clin. 60, 277-300 (2010).
2. Cohen HT, McGovern FJ: Renal-cell car (Pubitemid 41770167)
3. Zambrano NR, Lubensky IA, Merino MJ, Linehan WM, Walther MM: Histopathology and molecular genetics of renal tumors: toward unification of a classification system. J. Urol. 162, 1246-1258 (1999). (Pubitemid 29428557)
4. Herr H, Lamm DL, Denis L: Management of superficial bladder cancer. In:Principles & Practice of Genitourinary Oncology. Raghavan D, Scher HL, Leibel SA, Lange PH (Eds). Lippincott-Raven, PA, USA, 273-280 (1997).
5. Cairns P, Sidransky D: Bladder Cancer, 2nd Edition. New York McGraw-Hill, NY, USA (2002).
6. Dalgliesh GL, Furge K, Greenman C et al.: Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes. Nature 463, 360-363 (2010).
7. Thomas RK, Baker AC, Debiasi RM et al.: High-throughput oncogene mutation profiling in human cancer. Nat. Genet. 39, 347-351 (2007). (Pubitemid 46328493)
8. Beroukhim R, Brunet JP, Di Napoli A et al.: Patterns of gene expression and copy-number alterations in von-Hippel Lindau disease-associated and sporadic clear cell carcinoma of the kidney. Cancer Res. 69, 4674-4681 (2009).
9. Hoque MO, Lee CC, Cairns P, Schoenberg M, Sidransky D: Genome-wide genetic characterization of bladder cancer: a comparison of high-density single-nucleotide polymorphism arrays and PCR-based microsatellite analysis. Cancer Res. 63, 2216-2222 (2003). (Pubitemid 36538629)
10. Jones PA, Baylin SB: The fundamental role of epigenetic events in cancer. Nat. Rev. Genet. 3, 415-428 (2002). (Pubitemid 34587077)
11. Dunn BK: Hypomethylation: one side of a larger picture. Ann. NY Acad. Sci. 983, 28-42 (2003). (Pubitemid 36399318)
12. Cui H, Niemitz EL, Ravenel JD et al.: Loss of imprinting of insulin-like growth factor-II in Wilms' tumor commonly involves altered methylation but not mutations of CTCF or its binding site. Cancer Res. 61, 4947-4950 (2001). (Pubitemid 32681515)
13. Cui H, Onyango P, Brandenburg S, Wu Y, Hsieh CL, Feinberg AP: Loss of imprinting in colorectal cancer linked to hypomethylation of H19 and IGF2. Cancer Res. 62, 6442-6446 (2002). (Pubitemid 35364103)
14. Byun HM, Wong HL, Birnstein EA, Wolff EM, Liang G, Yang AS: Examination of IGF2 and H19 loss of imprinting in bladder cancer. Cancer Res. 67, 10753-10758 (2007). (Pubitemid 350145902)
15. Herman JG, Latif F, Weng Y et al.: Silencing of the VHL tumor-suppressor gene by DNA methylation in renal carcinoma. Proc. Natl Acad. Sci. USA 91, 9700-9704 (1994). (Pubitemid 24311875)
16. Dulaimi E, Ibanez de Caceres I, Uzzo RG et al.: Promoter hypermethylation profile of kidney cancer. Clin. Cancer Res. 10, 3972-3979 (2004). (Pubitemid 38812470)
17. Schmidt L, Duh FM, Chen F et al.: Germline and somatic mutations in the tyrosine kinase domain of the MET proto-oncogene in papillary renal carcinomas. Nat. Genet. 16, 68-73 (1997). (Pubitemid 27198158)
18. Tomlinson IP, Alam NA, Rowan AJ et al.: Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer. Nat. Genet. 30, 406-410 (2002).
19. Nickerson ML, Warren MB, Toro JR et al.: Mutations in a novel gene lead to kidney tumors, lung wall defects, and benign tumors of the hair follicle in patients with the Birt-Hogg-Dube syndrome. Cancer Cell 2, 157-164 (2002). (Pubitemid 41039116)
20. da Silva NF, Gentle D, Hesson LB, Morton DG, Latif F, Maher ER: Analysis of the Birt-Hogg-Dube (BHD) tumour suppressor gene in sporadic renal cell carcinoma and colorectal cancer. J. Med. Genet. 40, 820-824 (2003). (Pubitemid 37485492)
21. Gad S, Lefevre SH, Khoo SK et al.: Mutations in BHD and TP53 genes, but not in HNF1b gene, in a large series of sporadic chromophobe renal cell carcinoma. Br. J. Cancer 96, 336-340 (2007). (Pubitemid 46160640)
22. Ricketts C, Woodward ER, Killick P et al.: Germline SDHB mutations and familial renal cell carcinoma. J. Natl Cancer Inst. 100, 1260-1262 (2008).
23. Morris MR, Hesson LB, Wagner KJ et al.: Multigene methylation analysis of Wilms' tumour and adult renal cell carcinoma. Oncogene 22, 6794-6801 (2003). (Pubitemid 37372219)
24. Lynch HT, Smyrk TC, Watson P et al.: Genetics, natural history, tumor spectrum, and pathology of hereditary nonpolyposis colorectal cancer: an updated review. Gastroenterology 104, 1535-1549 (1993). (Pubitemid 23235432)
25. Gylling AH, Nieminen TT, Abdel-Rahman WM et al.: Differential cancer predisposition in Lynch syndrome: insights from molecular analysis of brain and urinary tract tumors. Carcinogenesis 29, 1351-1359 (2008).
26. Herman JG, Umar A, Polyak K et al.: Incidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinoma. Proc. Natl Acad. Sci. USA 95, 6870-6875 (1998). (Pubitemid 28278073)
27. Catto JW, Azzouzi AR, Rehman I et al.: Promoter hypermethylation is associated with tumor location, stage, and subsequent progression in transitional cell carcinoma. J. Clin. Oncol. 23, 2903-2910 (2005). (Pubitemid 46224108)
28. Esteller M, Levine R, Baylin SB, Ellenson LH, Herman JG: MLH1 promoter hypermethylation is associated with the microsatellite instability phenotype in sporadic endometrial carcinomas. Oncogene 17, 2413-2417 (1998). (Pubitemid 28515395)
29. Esteller M, Catasus L, Matias-Guiu X et al.: hMLH1 promoter hypermethylation is an early event in human endometrial tumorigenesis. Am. J. Pathol. 155, 1767-1772 (1999).
30. Haibach H, Burns TW, Carlson HE, Burman KD, Deftos LJ: Multiple hamartoma syndrome (Cowden's disease) associated with renal cell carcinoma and primary neuroendocrine carcinoma of the skin (Merkel cell carcinoma). Am. J. Clin. Pathol. 97, 705-712 (1992).
31. Pilarski R, Eng C: Will the real Cowden syndrome please stand up (again)? Expanding mutational and clinical spectra of the PTEN hamartoma tumour syndrome. J. Med. Genet. 41, 323-326 (2004). (Pubitemid 38608513)
32. Liaw D, Marsh DJ, Li J et al.: Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome. Nat. Genet. 16, 64-67 (1997). (Pubitemid 27198157)
33. Cairns P, Evron E, Okami K et al.: Point mutation and homozygous deletion of PTEN/ MMAC1 in primary bladder cancers. Oncogene 16, 3215-3218 (1998). (Pubitemid 28318794)
34. Zysman MA, Chapman WB, Bapat B: Considerations when analyzing the methylation status of PTEN tumor suppressor gene. Am. J. Pathol. 160, 795-800 (2002). (Pubitemid 34224569)
35. Niida Y, Stemmer-Rachamimov AO, Logrip M et al.: Survey of somatic mutations in tuberous sclerosis complex (TSC) hamartomas suggests different genetic mechanisms for pathogenesis of TSC lesions. Am. J. Hum. Genet. 69, 493-503 (2001). (Pubitemid 32777689)
36. Rocco JW, Sidransky D: p16(MTS-1/ CDKN2/INK4a) in cancer progression. Exp. Cell Res. 264, 42-55 (2001).
37. Herman JG, Merlo A, Mao L et al.: Inactivation of the CDKN2/p16/MTS1 gene is frequently associated with aberrant DNA methylation in all common human cancers. Cancer Res. 55, 4525-4530 (1995).
38. Smiraglia DJ, Rush LJ, Fruhwald MC et al.: Excessive CpG island hypermethylation in cancer cell lines versus primary human malignancies. Hum. Mol. Genet. 10, 1413-1419 (2001). (Pubitemid 32640670)
39. 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. 10, 1887-1893 (2004). (Pubitemid 38375544)
40. Robertson KD, Jones PA: The human ARF cell cycle regulatory gene promoter is a CpG island which can be silenced by DNA methylation and down-regulated by wild-type p53. Mol. Cell Biol. 18, 6457-6473 (1998). (Pubitemid 28500536)
41. Esteller M, Corn PG, Baylin SB, Herman JG: A gene hypermethylation profile of human cancer. Cancer Res. 61, 3225-3229 (2001). (Pubitemid 32695003)
42. Esteller M, Sparks A, Toyota M et al.: Analysis of adenomatous polyposis coli promoter hypermethylation in human cancer. Cancer Res. 60, 4366-4371 (2000). (Pubitemid 32103613)
43. Maruyama R, Toyooka S, Toyooka KO et al.: Aberrant promoter methylation profile of bladder cancer and its relationship to clinicopathological features. Cancer Res. 61, 8659-8663 (2001). (Pubitemid 34013873)
44. Neuhausen A, Florl AR, Grimm MO, Schulz WA: DNA methylation alterations in urothelial carcinoma. Cancer Biol. Ther. 5, 993-1001 (2006).
45. Becker KF, Atkinson MJ, Reich U et al.: E-cadherin gene mutations provide clues to diffuse type gastric carcinomas. Cancer Res. 54, 3845-3852 (1994). (Pubitemid 24241205)
46. Guilford P, Hopkins J, Harraway J et al.: E-cadherin germline mutations in familial gastric cancer. Nature 392, 402-405 (1998). (Pubitemid 28168738)
47. Grady WM, Willis J, Guilford PJ et al.: Methylation of the CDH1 promoter as the second genetic hit in hereditary diffuse gastric cancer. Nat. Genet. 26, 16-17 (2000).
48. Kawakami T, Okamoto K, Ogawa O, Okada Y: Multipoint methylation and expression analysis of tumor suppressor genes in human renal cancer cells. Urology 61, 226-230 (2003). (Pubitemid 36151757)
49. Chung WB, Hong SH, Kim JA, Sohn YK, Kim BW, Kim JW: Hypermethylation of tumor-related genes in genitourinary cancer cell lines. J. Korean Med. Sci. 16, 756-761 (2001).
50. Ribeiro-Filho LA, Franks J, Sasaki M et al.: CpG hypermethylation of promoter region and inactivation of E-cadherin gene in human bladder cancer. Mol. Carcinog. 34, 187-198 (2002). (Pubitemid 34840002)
51. Reinhold WC, Reimers MA, Maunakea AK et al.: Detailed DNA methylation profiles of the E-cadherin promoter in the NCI-60 cancer cells. Mol. Cancer Ther. 6, 391-403 (2007). (Pubitemid 46332442)
52. Stirzaker C, Millar DS, Paul CL et al.: Extensive DNA methylation spanning the Rb promoter in retinoblastoma tumors. Cancer Res. 57, 2229-2237 (1997). (Pubitemid 27247043)
53. Bachman KE, Herman JG, Corn PG et al.: Methylation-associated silencing of the tissue inhibitor of metalloproteinase-3 gene suggest a suppressor role in kidney, brain, and other human cancers. Cancer Res. 59, 798-802 (1999). (Pubitemid 29086729)
54. Kagan J, Srivastava S, Barker PE, Belinsky SA, Cairns P: Towards clinical application of methylated DNA sequences as cancer biomarkers: a joint NCI's EDRN and NIST workshop on standards, methods, assays, reagents and tools. Cancer Res. 67, 4545-4549 (2007). (Pubitemid 46910155)
55. Dammann R, Li C, Yoon JH, Chin PL, Bates S, Pfeifer GP: Epigenetic inactivation of a RAS association domain family protein from the lung tumour suppressor locus 3p21.3. Nat. Genet. 25, 315-319 (2000). (Pubitemid 30437320)
56. Dreijerink K, Braga E, Kuzmin I et al.: The candidate tumor suppressor gene, RASSF1A, from human chromosome 3p21.3 is involved in kidney tumorigenesis. Proc. Natl Acad. Sci. USA 98, 7504-7509 (2001). (Pubitemid 32567978)
57. Morrissey C, Martinez A, Zatyka M et al.: Epigenetic inactivation of the RASSF1A 3p21.3 tumor suppressor gene in both clear cell and papillary renal cell carcinoma. Cancer Res. 61, 7277-7281 (2001). (Pubitemid 32946526)
58. Yoon JH, Dammann R, Pfeifer GP: Hypermethylation of the CpG island of the RASSF1A gene in ovarian and renal cell carcinomas. Int. J. Cancer 94, 212-217 (2001). (Pubitemid 32911415)
59. Chan MW, Chan LW, Tang NL et al.: Frequent hypermethylation of promoter region of RASSF1A in tumor tissues and voided urine of urinary bladder cancer patients. Int. J. Cancer 104, 611-616 (2003). (Pubitemid 36337261)
60. Lee MG, Kim HY, Byun DS et al.: Frequent epigenetic inactivation of RASSF1A in human bladder carcinoma. Cancer Res. 61, 6688-6692 (2001).
61. Lee WH, Morton RA, Epstein JI et al.: Cytidine methylation of regulatory sequences near the pi-class glutathione S-transferase gene accompanies human prostatic carcinogenesis. Proc. Natl Acad. Sci. USA 91, 11733-11737 (1994). (Pubitemid 24356419)
62. Chan MW, Chan LW, Tang NL et al.: Hypermethylation of multiple genes in tumor tissues and voided urine in urinary bladder cancer patients. Clin. Cancer Res. 8, 464-470 (2002). (Pubitemid 34193966)
63. Esteller M, Corn PG, Urena JM, Gabrielson E, Baylin SB, Herman JG: Inactivation of glutathione S-transferase P1 gene by promoter hypermethylation in human neoplasia. Cancer Res. 58, 4515-4518 (1998). (Pubitemid 28480605)
64. Esteller M, Hamilton SR, Burger PC, Baylin SB, Herman JG: Inactivation of the DNA repair gene O6-methylguanine-DNA methyltransferase by promoter hypermethylation is a common event in primary human neoplasia. Cancer Res. 59, 793-797 (1999). (Pubitemid 29086728)
65. Hoque MO, Begum S, Topaloglu O et al.: Quantitative detection of promoter hypermethylation of multiple genes in the tumor, urine, and serum DNA of patients with renal cancer. Cancer Res. 64, 5511-5517 (2004). (Pubitemid 39006576)
66. Kissil JL, Feinstein E, Cohen O et al.: DAP-kinase loss of expression in various carcinoma and B-cell lymphoma cell lines: possible implications for role as tumor suppressor gene. Oncogene 15, 403-407 (1997). (Pubitemid 27370989)
67. Katzenellenbogen RA, Baylin SB, Herman JG: Hypermethylation of the DAP-kinase CpG island is a common alteration in B-cell malignancies. Blood 93, 4347-4353 (1999). (Pubitemid 29279278)
68. Gonzalgo ML, Yegnasubramanian S, Yan G et al.: Molecular profiling and classification of sporadic renal cell carcinoma by quantitative methylation analysis. Clin. Cancer Res. 10, 7276-7283 (2004). (Pubitemid 39487715)
69. Wethkamp N, Ramp U, Geddert H et al.: Expression of death-associated protein kinase during tumour progression of human renal cell carcinomas: hypermethylation-independent mechanisms of inactivation. Eur. J. Cancer 42, 264-274 (2006). (Pubitemid 43083499)
70. Tada Y, Wada M, Taguchi K et al.: The association of death-associated protein kinase hypermethylation with early recurrence in superficial bladder cancers. Cancer Res. 62, 4048-4053 (2002). (Pubitemid 34791073)
71. Christoph F, Kempkensteffen C, Weikert S 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 95, 1701-1707 (2006). (Pubitemid 44950797)
72. Marsit CJ, Houseman EA, Christensen BC et al.: Examination of a CpG island methylator phenotype and implications of methylation profiles in solid tumors. Cancer Res. 66, 10621-10629 (2006). (Pubitemid 44799786)
73. Sathyanarayana UG, Maruyama R, Padar 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. 64, 1425-1430 (2004). (Pubitemid 38235612)
74. Takahashi T, Suzuki M, Shigematsu H et al.: Aberrant methylation of Reprimo in human malignancies. Int. J. Cancer 115, 503-510 (2005). (Pubitemid 40656706)
75. Iliopoulos D, Guler G, Han SY et al.: Fragile genes as biomarkers: epigenetic control of WWOX and FHIT in lung, breast and bladder cancer. Oncogene 24, 1625-1633 (2005). (Pubitemid 40396092)
76. Kvasha S, Gordiyuk V, Kondratov A et al.: Hypermethylation of the 5́CpG island of the FHIT gene in clear cell renal carcinomas. Cancer Lett. 265, 250-257 (2008).
77. Morris MR, Gentle D, Abdulrahman M et al.: Tumor suppressor activity and epigenetic inactivation of hepatocyte growth factor activator inhibitor type 2/SPINT2 in papillary and clear cell renal cell carcinoma. Cancer Res. 65, 4598-4606 (2005). (Pubitemid 40740795)
78. Agathanggelou A, Dallol A, Zochbauer-Muller S et al.: Epigenetic inactivation of the candidate 3p21.3 suppressor gene BLU in human cancers. Oncogene 22, 1580-1588 (2003). (Pubitemid 36390607)
79. Stoehr R, Wissmann C, Suzuki H et al.: Deletions of chromosome 8p and loss of sFRP1 expression are progression markers of papillary bladder cancer. Lab. Invest. 84, 465-478 (2004). (Pubitemid 41656474)
80. Marsit CJ, Karagas MR, Andrew A et al.: Epigenetic inactivation of SFRP genes and TP53 alteration act jointly as markers of invasive bladder cancer. Cancer Res. 65, 7081-7085 (2005). (Pubitemid 41161235)
81. Dahl E, Wiesmann F, Woenckhaus M et al.: Frequent loss of SFRP1 expression in multiple human solid tumours: association with aberrant promoter methylation in renal cell carcinoma. Oncogene 26, 5680-5691 (2007). (Pubitemid 47267837)
82. Kagara I, Enokida H, Kawakami K et al.: CpG hypermethylation of the UCHL1 gene promoter is associated with pathogenesis and poor prognosis in renal cell carcinoma. J. Urol. 180, 343-351 (2008).
83. Urakami S, Shiina H, Enokida H et al.: Combination analysis of hypermethylated Wnt-antagonist family genes as a novel epigenetic biomarker panel for bladder cancer detection. Clin. Cancer Res. 12, 2109-2116 (2006).
84. de Caestecker MP, Piek E, Roberts AB: Role of transforming growth factor-b signaling in cancer. J. Natl Cancer Inst. 92, 1388-1402 (2000).
85. Roberts AB, Wakefield LM: The two faces of transforming growth factor b in carcinogenesis. Proc. Natl Acad. Sci. USA 100, 8621-8623 (2003). (Pubitemid 36899145)
86. Teicher BA: Malignant cells, directors of the malignant process: role of transforming growth factor-b. Cancer Metastasis Rev. 20, 133-143 (2001). (Pubitemid 34074689)
87. Suzuki M, Shigematsu H, Shames DS et al.: DNA methylation-associated inactivation of TGFb-related genes DRM/Gremlin, RUNX3, and HPP1 in human cancers. Br. J. Cancer 93, 1029-1037 (2005). (Pubitemid 41548398)
88. Okuda H, Toyota M, Ishida W et al.: Epigenetic inactivation of the candidate tumor suppressor gene HOXB13 in human renal cell carcinoma. Oncogene 25, 1733-1742 (2006).
89. Yamada D, Kikuchi S, Williams YN et al.: Promoter hypermethylation of the potential tumor suppressor DAL-1/4.1B gene in renal clear cell carcinoma. Int. J. Cancer 118, 916-923 (2006). (Pubitemid 43157666)
90. To KK, Zhan Z, Bates SE: Aberrant promoter methylation of the ABCG2 gene in renal carcinoma. Mol. Cell Biol. 26, 8572-8585 (2006). (Pubitemid 44748589)
91. Kawakami T, Chano T, Minami K, Okabe H, Okada Y, Okamoto K: Imprinted DLK1 is a putative tumor suppressor gene and inactivated by epimutation at the region upstream of GTL2 in human renal cell carcinoma. Hum. Mol. Genet. 15, 821-830 (2006). (Pubitemid 43338225)
92. Reu FJ, Bae SI, Cherkassky L et al.: Overcoming resistance to interferon-induced apoptosis of renal carcinoma and melanoma cells by DNA demethylation. J. Clin. Oncol. 24, 3771-3779 (2006). (Pubitemid 46622316)
93. Lee MG, Huh JS, Chung SK et al.: Promoter CpG hypermethylation and downregulation of XAF1 expression in human urogenital malignancies: implication for attenuated p53 response to apoptotic stresses. Oncogene 25, 5807-5822 (2006).
94. Kempkensteffen C, Hinz S, Schrader M et al.: Gene expression and promoter methylation of the XIAP-associated factor 1 in renal cell carcinomas: correlations with pathology and outcome. Cancer Lett. 254, 227-235 (2007). (Pubitemid 47135616)
95. Ibanez de Caceres I, Dulaimi E, Hoffman AM, Al-Saleem T, Uzzo RG, Cairns P: Identification of novel target genes by an epigenetic reactivation screen of renal cancer. Cancer Res. 66, 5021-5028 (2006). (Pubitemid 43844922)
96. Agathanggelou A, Bieche I, Ahmed-Choudhury J et al.: Identification of novel gene expression targets for the Ras association domain family 1 (RASSF1A) tumor suppressor gene in non-small-cell lung cancer and neuroblastoma. Cancer Res. 63, 5344-5351 (2003). (Pubitemid 37139849)
97. Mori K, Enokida H, Kagara I et al.: CpG hypermethylation of collagen type I a2 contributes to proliferation and migration activity of human bladder cancer. Int. J. Oncol. 34, 1593-1602 (2009).
98. Liang G, Gonzales FA, Jones PA, Orntoft TF, Thykjaer T: Analysis of gene induction in human fibroblasts and bladder cancer cells exposed to the methylation inhibitor 5-aza-2́-deoxycytidine. Cancer Res. 62, 961-966 (2002). (Pubitemid 34160269)
99. Suzuki H, Gabrielson E, Chen W et al.: A genomic screen for genes upregulated by demethylation and histone deacetylase inhibition in human colorectal cancer. Nat. Genet. 31, 141-149 (2002).
100. Morris MR, Gentle D, Abdulrahman M et al.: Functional epigenomics approach to identify methylated candidate tumour suppressor genes in renal cell carcinoma. Br. J. Cancer 98, 496-501 (2008). (Pubitemid 351161264)
101. Morris MR, Ricketts C, Gentle D et al.: Identification of candidate tumour suppressor genes frequently methylated in renal cell carcinoma. Oncogene 29, 2104-2117 (2010).
102. Seliger B, Handke D, Schabel E, Bukur J, Lichtenfels R, Dammann R: Epigenetic control of the ubiquitin carboxyl terminal hydrolase 1 in renal cell carcinoma. J. Transl. Med. 7, 90 (2009).
103. Dalgin GS, Drever M, Williams T, King T, DeLisi C, Liou LS: Identification of novel epigenetic markers for clear cell renal cell carcinoma. J. Urol. 180, 1126-1130 (2008).
104. McRonald FE, Morris MR, Gentle D et al.: CpG methylation profiling in VHL related and VHL unrelated renal cell carcinoma. Mol. Cancer 8, 31 (2009).
105. Wu G, Guo Z, Chang X et al.: LOXL1 and LOXL4 are epigenetically silenced and can inhibit ras/extracellular signal-regulated kinase signaling pathway in human bladder cancer. Cancer Res. 67, 4123-4129 (2007). (Pubitemid 46815057)
106. Veerla S, Panagopoulos I, Jin Y, Lindgren D, Hoglund M: Promoter analysis of epigenetically controlled genes in bladder cancer. Genes Chromosomes Cancer 47, 368-378 (2008). (Pubitemid 351451791)
107. Cairns P: Gene methylation and early detection of genitourinary cancer: the road ahead. Nat. Rev. Cancer 7, 531-543 (2007). (Pubitemid 46985397)
108. Teodoridis JM, Hardie C, Brown R: CpG island methylator phenotype (CIMP) in cancer: causes and imp000lications. Cancer Lett. 268, 177-186 (2008).
109. Zhang L, Yu J, Willson JK, Markowitz SD, Kinzler KW, Vogelstein B: Short mononucleotide repeat sequence variability in mismatch repair-deficient cancers. Cancer Res. 61, 3801-3805 (2001). (Pubitemid 32694996)
110. Esteller M: Epigenetics in cancer. N. Engl. J. Med. 358, 1148-1159 (2008).
111. Nguyen CT, Weisenberger DJ, Velicescu M et al.: Histone H3-lysine 9 methylation is associated with aberrant gene silencing in cancer cells and is rapidly reversed by 5-aza-2́-deoxycytidine. Cancer Res. 62, 6456-6461 (2002). (Pubitemid 35364106)
112. Fraga MF, Ballestar E, Villar-Garea A et al.: Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer. Nat. Genet. 37, 391-400 (2005).
113. Ozdag H, Teschendorff AE, Ahmed AA et al.: Differential expression of selected histone modifier genes in human solid cancers. BMC Genomics 7, 90 (2006).
114. Stransky N, Vallot C, Reyal F et al.: Regional copy number-independent deregulation of transcription in cancer. Nat. Genet. 38, 1386-1396 (2006). (Pubitemid 44837560)
115. Seligson DB, Horvath S, McBrian MA et al.: Global levels of histone modifications predict prognosis in different cancers. Am. J. Pathol. 174, 1619-1628 (2009).
116. Ellinger J, Kahl P, Mertens C et al.: Prognostic relevance of global histone H3 lysine 4 (H3K4) methylation in renal cell carcinoma. Int. J. Cancer 127, 2360-2366 (2010).
117. Lamy P, Andersen CL, Dyrskjot L, Torring N, Orntoft T, Wiuf C: Are microRNAs located in genomic regions associated with cancer? Br. J. Cancer 95, 1415-1418 (2006). (Pubitemid 44760095)
118. Saito Y, Jones PA: Epigenetic activation of tumor suppressor microRNAs in human cancer cells. Cell Cycle 5, 2220-2222 (2006). (Pubitemid 44546557)
119. Friedman JM, Liang G, Liu CC et al.: The putative tumor suppressor microRNA-101 modulates the cancer epigenome by repressing the polycomb group protein EZH2. Cancer Res. 69, 2623-2629 (2009).
120. Catto JW, Miah S, Owen HC et al.: Distinct microRNA alterations characterize high-and low-grade bladder cancer. Cancer Res. 69, 8472-8481 (2009).
121. Dyrskjot L, Ostenfeld MS, Bramsen JB et al.: Genomic profiling of microRNAs in bladder cancer: miR-129 is associated with poor outcome and promotes cell death in vitro. Cancer Res. 69, 4851-4860 (2009).
122. Wiklund ED, Bramsen JB, Hulf T et al.: Coordinated epigenetic repression of the miR-200 family and miR-205 in invasive bladder cancer. Int. J. Cancer (2010) (Epub ahead of print).
123. Jung M, Mollenkopf HJ, Grimm C et al.: MicroRNA profiling of clear cell renal cell cancer identifies a robust signature to define renal malignancy. J. Cell. Mol. Med. 13, 3918-3928 (2009).
124. Nakada C, Matsuura K, Tsukamoto Y et al.: Genome-wide microRNA expression profiling in renal cell carcinoma: significant down-regulation of miR-141 and miR-200c. J. Pathol. 216, 418-427 (2008).
125. Juan D, Alexe G, Antes T et al.: Identification of a microRNA panel for clear-cell kidney cancer. Urology 75(4), 835-841 (2010).
126. Banumathy G, Cairns P: Signaling pathways in renal cell carcinoma. Cancer Biol. Ther. 10(7), 658-664 (2010).
127. Battagli C, Uzzo RG, Dulaimi E et al.: Promoter hypermethylation of tumor suppressor genes in urine from kidney cancer patients. Cancer Res. 63, 8695-8699 (2003). (Pubitemid 38064046)
128. Friedrich MG, Weisenberger DJ, Cheng JC et al.: Detection of methylated apoptosis-associated genes in urine sediments of bladder cancer patients. Clin. Cancer Res. 10, 7457-7465 (2004). (Pubitemid 39557507)
129. Hoque MO, Begum S, Topaloglu O et al.: Quantitation of promoter methylation of multiple genes in urine DNA and bladder cancer detection. J. Natl Cancer Inst. 98, 996-1004 (2006). (Pubitemid 44288164)
130. 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 25, 1984-1988 (2006).
131. Renard I, Joniau S, van Cleynenbreugel B et al.: Identification and validation of the methylated TWIST1 and NID2 genes through real-time methylation-specific polymerase chain reaction assays for the noninvasive detection of primary bladder cancer in urine samples. Eur. Urol. 58(1), 96-104 (2009).
132. Costa VL, Henrique R, Ribeiro FR et al.: Quantitative promoter methylation analysis of multiple cancer-related genes in renal cell tumors. BMC Cancer 7, 133 (2007).
133. Gutierrez MI, Siraj AK, Khaled H, Koon N, El-Rifai W, Bhatia K: CpG island methylation in schistosoma-and non-schistosoma-associated bladder cancer. Mod. Pathol. 17, 1268-1274 (2004). (Pubitemid 39312953)
134. Breault JE, Shiina H, Igawa M et al.: Methylation of the g-catenin gene is associated with poor prognosis of renal cell carcinoma. Clin. Cancer Res. 11, 557-564 (2005). (Pubitemid 40116880)
135. Yates DR, Rehman I, Abbod MF et al.: Promoter hypermethylation identifies progression risk in bladder cancer. Clin. Cancer Res. 13, 2046-2053 (2007). (Pubitemid 46649871)
136. Gollob JA, Sciambi CJ, Peterson BL et al.: Phase I trial of sequential low-dose 5-aza-2'-deoxycytidine plus high-dose intravenous bolus interleukin-2 in patients with melanoma or renal cell carcinoma. Clin. Cancer Res. 12, 4619-4627 (2006). (Pubitemid 44297813)
137. Winquist E, Knox J, Ayoub JP et al.: Phase II trial of DNA methyltransferase 1 inhibition with the antisense oligonucleotide MG98 in patients with metastatic renal carcinoma: a National Cancer Institute of Canada Clinical Trials Group investigational new drug study. Invest. New Drugs 24, 159-167 (2006). (Pubitemid 43723908)
138. Hammers HJ, Verheul H, Wilky B et al.: Phase I safety and pharmacokinetic/ pharmacodynamic results of the histone deacetylase inhibitor vorinostat in combination with bevacizumab in patients with kidney cancer. J. Clin. Oncol. 26, (2008) (Abstract 16094).
139. Verheul HM, Salumbides B, van Erp K et al.: Combination strategy targeting the hypoxia inducible factor-1 a with mammalian target of rapamycin and histone deacetylase inhibitors. Clin. Cancer Res. 14, 3589-3597 (2008).
140. Shang D, Liu Y, Matsui Y et al.: Demethylating agent 5-aza-2́- deoxycytidine enhances susceptibility of bladder transitional cell carcinoma to cisplatin. Urology 71, 1220-1225 (2008). (Pubitemid 351763776)
141. Costello JF, Frühwald MC, Smiraglia DJ et al.: Aberrant CpG-island methylation has non-random and tumour-type-specific patterns. Nature Genet. 25, 132-138 (2000). (Pubitemid 30094712)
142. Sjoblom T, Jones S, Wood LD et al.: The consensus coding sequences of human breast and colorectal cancers. Science 314, 268-274 (2006). (Pubitemid 44571966)
143. Aleman A, Cebrian V, Alvarez M et al.: Identification of PMF1 methylation in association with bladder cancer progression. Clin. Cancer Res. 14, 8236-8243 (2008).
144. Kwabi-Addo B, Chung W, Shen L et al.: Age-related DNA methylation changes in normal human prostate tissues. Clin. Cancer Res. 13, 3796-3802 (2007). (Pubitemid 47037584)
145. Wolff EM, Liang G, Cortez CC et al.: RUNX3 methylation reveals that