Epigenetics of renal cell carcinoma: The path towards new diagnostics and therapeutics

Genome Medicine

Volumn 2, Issue 9, 2010, Pages

  Morris, Mark R ^a   Maher, Eamonn R ^a,b  

^a UNIVERSITY OF BIRMINGHAM   (United Kingdom)

^b BIRMINGHAM WOMEN S HOSPITAL   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

5 AZA 2' DEOXYCYTIDINE; BETA CATENIN; BISULFITE; FRAGILE HISTIDINE TRIAD PROTEIN; RAS ASSOCIATION DOMAIN FAMILY PROTEIN 1A; TUMOR MARKER; VON HIPPEL LINDAU PROTEIN; WNT PROTEIN;

CANCER DIAGNOSIS; CANCER GROWTH; DNA METHYLATION; EPIGENETICS; GENE MUTATION; GENE SEQUENCE; GENETIC ANALYSIS; HUMAN; KIDNEY CARCINOMA; MYELODYSPLASTIC SYNDROME; PRIORITY JOURNAL; PROGNOSIS; PROTEIN METHYLATION; REVIEW; TUMOR SUPPRESSOR GENE;

EID: 78751681420     PISSN: None     EISSN: 1756994X     Source Type: Journal    
DOI: 10.1186/gm180     Document Type: Review

References (121)

1. Ferlay J, Autier P, Boniol M, Heanue M, Colombet M, Boyle P. Estimates of the cancer incidence and mortality in Europe in 2006. Ann Oncol 2007, 18:581-592.
2. Mancini V, Battaglia M, Ditonno P, Palazzo S, Lastilla G, Montironi R, Bettocchi C, Cavalcanti E, Ranieri E, Selvaggi FP. Current insights in renal cell cancer pathology. Urol Oncol 2008, 26:225-238.
3. Clifford SC, Prowse AH, Affara NA, Buys CH, Maher ER. Inactivation of the von Hippel-Lindau (VHL) tumour suppressor gene and allelic losses at chromosome arm 3p in primary renal cell carcinoma: evidence for a VHL-independent pathway in clear cell renal tumourigenesis. Genes Chromosomes Cancer 1998, 22:200-209.
4. Foster K, Crossey PA, Cairns P, Hetherington JW, Richards FM, Jones MH, Bentley E, Affara NA, Ferguson-Smith MA, Maher ER. Molecular genetic investigation of sporadic renal cell carcinoma: analysis of allele loss on chromosomes 3p, 5q, 11p, 17 and 22. Br J Cancer 1994, 69:230-234. 1968700, 8297719.
5. Herman JG, Latif F, Weng Y, Lerman MI, Zbar B, Liu S, Samid D, Duan DS, Gnarra JR, Linehan WM. Silencing of the VHL tumor-suppressor gene by DNA methylation in renal carcinoma. Proc Natl Acad Sci USA 1994, 91:9700-9704. 44884, 7937876.
6. Latif F, Tory K, Gnarra J, Yao M, Duh FM, Orcutt ML, Stackhouse T, Kuzmin I, Modi W, Geil L. Identification of the von Hippel-Lindau disease tumor suppressor gene. Science 1993, 260:1317-1320.
7. Maxwell PH, Wiesener MS, Chang GW, Clifford SC, Vaux EC, Cockman ME, Wykoff CC, Pugh CW, Maher ER, Ratcliffe PJ. The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature 1999, 399:271-275.
8. Maher ER, Yates JR, Ferguson-Smith MA. Statistical analysis of the two stage mutation model in von Hippel-Lindau disease, and in sporadic cerebellar haemangioblastoma and renal cell carcinoma. J Med Genet 1990, 27:311-314. 1017082, 2352258.
9. Banks RE, Tirukonda P, Taylor C, Hornigold N, Astuti D, Cohen D, Maher ER, Stanley AJ, Harnden P, Joyce A, Knowles M, Selby PJ. Genetic and epigenetic analysis of von Hippel-Lindau (VHL) gene alterations and relationship with clinical variables in sporadic renal cancer. Cancer Res 2006, 66:2000-2011.
10. Catalogue of Somatic Mutations in Cancer. , http://www.sanger.ac.uk/genetics/CGP/cosmic/
11. Bird A. DNA methylation patterns and epigenetic memory. Genes Dev 2002, 16:6-21.
12. Nguyen CT, Gonzales FA, Jones PA. Altered chromatin structure associated with methylation-induced gene silencing in cancer cells: correlation of accessibility, methylation, MeCP2 binding and acetylation. Nucleic Acids Res 2001, 29:4598-4606. 92514, 11713309.
13. Fahrner JA, Eguchi S, Herman JG, Baylin SB. Dependence of histone modifications and gene expression on DNA hypermethylation in cancer. Cancer Res 2002, 62:7213-7218.
14. Ballestar E, Paz MF, Valle L, Wei S, Fraga MF, Espada J, Cigudosa JC, Huang TH-M, Esteller M. Methyl-CpG binding proteins identify novel sites of epigenetic inactivation in human cancer. EMBO J 2003, 22:6335-6345. 291845, 14633992.
15. Fraga MF, Ballestar E, Villar-Garea A, Boix-Chornet M, Espada J, Schotta G, Bonaldi T, Haydon C, Ropero S, Petrie K, Iyer NG, Pérez-Rosado A, Calvo E, Lopez JA, Cano A, Calasanz MJ, Colomer D, Piris MA, Ahn N, Imhof A, Caldas C, Jenuwein T, Esteller M. Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer. Nat Genet 2005, 37:391-400.
16. Pruitt K, Zinn RL, Ohm JE, McGarvey KM, Kang S-HL, Watkins DN, Herman JG, Baylin SB. Inhibition of SIRT1 reactivates silenced cancer genes without loss of promoter DNA hypermethylation. PLoS Genet 2006, 2:e40. 1420676, 16596166.
17. Jones PA, Taylor SM. Cellular differentiation, cytidine analogs and DNA methylation. Cell 1980, 20:85-93.
18. Issa J-PJ, Kantarjian HM. Targeting DNA methylation. Clin Cancer Res 2009, 15:3938-3946. 2732562, 19509174.
19. Kikuchi R, Yagi S, Kusuhara H, Imai S, Sugiyama Y, Shiota K. Genome-wide analysis of epigenetic signatures for kidney-specific transporters. Kidney Int 2010,
20. Sørensen AL, Jacobsen BM, Reiner AH, Andersen IS, Collas P. Promoter DNA methylation patterns of differentiated cells are largely programmed at the progenitor stage. Mol Biol Cell 2010, 21:2066-2077. 2883950, 20410135.
21. Bodey B. Cancer-testis antigens: promising targets for antigen directed antineoplastic immunotherapy. Expert Opin Biol Ther 2002, 2:577-584.
22. Reik W, Lewis A. Co-evolution of X-chromosome inactivation and imprinting in mammals. Nat Rev Genet 2005, 6:403-410.
23. Herman JG, Baylin SB. Gene silencing in cancer in association with promoter hypermethylation. N Engl J Med 2003, 349:2042-2054.
24. Feinberg AP, Tycko B. The history of cancer epigenetics. Nat Rev Cancer 2004, 4:143-153.
25. Egger G, Liang G, Aparicio A, Jones PA. Epigenetics in human disease and prospects for epigenetic therapy. Nature 2004, 429:457-463.
26. Esteller M. Aberrant DNA methylation as a cancer-inducing mechanism. Annu Rev Pharmacol Toxicol 2005, 45:629-656.
27. Nakagawa Y, Uemura H, Shimizu K, Cho M, Yoshikawa M, Hirao Y, Yoshikawa K. [The role of MN/CA IX antigen in carcinogenesis and metastasis of renal cell carcinoma]. Hinyokika Kiyo 2001, 47:809-814.
28. Esteller M, Catasus L, Matias-Guiu X, Mutter GL, Prat J, Baylin SB, Herman JG. hMLH1 promoter hypermethylation is an early event in human endometrial tumorigenesis. Am J Pathol 1999, 155:1767-1772. 1866976, 10550333.
29. Prowse AH, Webster AR, Richards FM, Richard S, Olschwang S, Resche F, Affara NA, Maher ER. Somatic inactivation of the VHL gene in Von Hippel-Lindau disease tumors. Am J Hum Genet 1997, 60:765-771. 1712486, 9106522.
30. Ongenaert M, van Neste L, De Meyer T, Menschaert G, Bekaert S, Van Criekinge W. PubMeth: a cancer methylation database combining text-mining and expert annotation. Nucleic Acids Res 2008, 36:D842-D846. 2238841, 17932060.
31. Kok K, Naylor SL, Buys CH. Deletions of the short arm of chromosome 3 in solid tumors and the search for suppressor genes. Adv Cancer Res 1997, 71:27-92.
32. Kovacs G, Frisch S. Clonal chromosome abnormalities in tumor cells from patients with sporadic renal cell carcinomas. Cancer Res 1989, 49:651-659.
33. Beroukhim R, Brunet J-P, Di Napoli A, Mertz KD, Seeley A, Pires MM, Linhart D, Worrell RA, Moch H, Rubin MA, Sellers WR, Meyerson M, Linehan WM, Kaelin WG, Signoretti S. Patterns of gene expression and copy-number alterations in von-Hippel Lindau disease-associated and sporadic clear cell carcinoma of the kidney. Cancer Res 2009, 69:4674-4681. 2745239, 19470766.
34. Young AC, Craven RA, Cohen D, Taylor C, Booth C, Harnden P, Cairns DA, Astuti D, Gregory W, Maher ER, Knowles MA, Joyce A, Selby PJ, Banks RE. Analysis of VHL gene alterations and their relationship to clinical parameters in sporadic conventional renal cell carcinoma. Clin Cancer Res 2009, 15:7582-7592. 2795746, 19996202.
35. Dulaimi E, Ibanez de Caceres I, Uzzo RG, Al-Saleem T, Greenberg RE, Polascik TJ, Babb JS, Grizzle WE, Cairns P. Promoter hypermethylation profile of kidney cancer. Clin Cancer Res 2004, 10:3972-3979.
36. Hori Y, Oda Y, Kiyoshima K, Yamada Y, Nakashima Y, Naito S, Tsuneyoshi M. Oxidative stress and DNA hypermethylation status in renal cell carcinoma arising in patients on dialysis. J Pathol 2007, 212:218-226.
37. Nickerson ML, Jaeger E, Shi Y, Durocher JA, Mahurkar S, Zaridze D, Matveev V, Janout V, Kollarova H, Bencko V, Navratilova M, Szeszenia-Dabrowska N, Mates D, Mukeria A, Holcatova I, Schmidt LS, Toro JR, Karami S, Hung R, Gerard GF, Linehan WM, Merino M, Zbar B, Boffetta P, Brennan P, Rothman N, Chow WH, Waldman FM, Moore LE. Improved identification of von Hippel-Lindau gene alterations in clear cell renal tumors. Clin Cancer Res 2008, 14:4726-4734. 2629664, 18676741.
38. Hesson LB, Cooper WN, Latif F. Evaluation of the 3p21.3 tumour-suppressor gene cluster. Oncogene 2007, 26:7283-7301.
39. Morrissey C, Martinez A, Zatyka M, Agathanggelou A, Honorio S, Astuti D, Morgan NV, Moch H, Richards FM, Kishida T, Yao M, Schraml P, Latif F, Maher ER. Epigenetic inactivation of the RASSF1A 3p21.3 tumor suppressor gene in both clear cell and papillary renal cell carcinoma. Cancer Res 2001, 61:7277-7281.
40. Lusher ME, Lindsey JC, Latif F, Pearson ADJ, Ellison DW, Clifford SC. Biallelic epigenetic inactivation of the RASSF1A tumor suppressor gene in medulloblastoma development. Cancer Res 2002, 62:5906-5911.
41. Battagli C, Uzzo RG, Dulaimi E, Ibanez de Caceres I, Krassenstein R, Al-Saleem T, Greenberg RE, Cairns P. Promoter hypermethylation of tumor suppressor genes in urine from kidney cancer patients. Cancer Res 2003, 63:8695-8699.
42. Onay H, Pehlivan S, Koyuncuoglu M, Kirkali Z, Ozkinay F. Multigene methylation analysis of conventional renal cell carcinoma. Urol Int 2009, 83:107-112.
43. Hoque MO, Begum S, Topaloglu O, Jeronimo C, Mambo E, Westra WH, Califano JA, Sidransky D. Quantitative detection of promoter hypermethylation of multiple genes in the tumor, urine, and serum DNA of patients with renal cancer. Cancer Res 2004, 64:5511-5517.
44. Costa VL, Henrique R, Ribeiro FR, Pinto M, Oliveira J, Lobo F, Teixeira MR, Jerónimo C. Quantitative promoter methylation analysis of multiple cancer-related genes in renal cell tumors. BMC Cancer 2007, 7:133. 1940017, 17645803.
45. Dreijerink K, Braga E, Kuzmin I, Geil L, Duh FM, Angeloni D, Zbar B, Lerman MI, Stanbridge EJ, Minna JD, Protopopov A, Li J, Kashuba V, Klein G, Zabarovsky ER. The candidate tumor suppressor gene, RASSF1A, from human chromosome 3p21.3 is involved in kidney tumorigenesis. Proc Natl Acad Sci USA 2001, 98:7504-7509. 34698, 11390984.
46. Gonzalgo ML, Yegnasubramanian S, Yan G, Rogers CG, Nicol TL, Nelson WG, Pavlovich CP. Molecular profiling and classification of sporadic renal cell carcinoma by quantitative methylation analysis. Clin Cancer Res 2004, 10:7276-7283.
47. Yoon JH, Dammann R, Pfeifer GP. Hypermethylation of the CpG island of the RASSF1A gene in ovarian and renal cell carcinomas. Int J Cancer 2001, 94:212-217.
48. Vanaja DK, Ballman KV, Morlan BW, Cheville JC, Neumann RM, Lieber MM, Tindall DJ, Young CYF. PDLIM4 repression by hypermethylation as a potential biomarker for prostate cancer. Clin Cancer Res 2006, 12:1128-1136.
49. van den Boom J, Wolter M, Blaschke B, Knobbe CB, Reifenberger G. Identification of novel genes associated with astrocytoma progression using suppression subtractive hybridization and real-time reverse transcription-polymerase chain reaction. Int J Cancer 2006, 119:2330-2338.
50. Awakura Y, Nakamura E, Ito N, Kamoto T, Ogawa O. Methylation-associated silencing of TU3A in human cancers. Int J Oncol 2008, 33:893-899.
51. Druck T, Hadaczek P, Fu TB, Ohta M, Siprashvili Z, Baffa R, Negrini M, Kastury K, Veronese ML, Rosen D, Rothstein J, McCue P, Cotticelli MG, Inoue H, Croce CM, Huebner K. Structure and expression of the human FHIT gene in normal and tumor cells. Cancer Res 1997, 57:504-512.
52. Sozzi G, Pastorino U, Moiraghi L, Tagliabue E, Pezzella F, Ghirelli C, Tornielli S, Sard L, Huebner K, Pierotti MA, Croce CM, Pilotti S. Loss of FHIT function in lung cancer and preinvasive bronchial lesions. Cancer Res 1998, 58:5032-5037.
53. Dumon KR, Ishii H, Fong LY, Zanesi N, Fidanza V, Mancini R, Vecchione A, Baffa R, Trapasso F, During MJ, Huebner K, Croce CM. FHIT gene therapy prevents tumor development in Fhit-deficient mice. Proc Natl Acad Sci USA 2001, 98:3346-3351. 30656, 11248081.
54. Kvasha S, Gordiyuk V, Kondratov A, Ugryn D, Zgonnyk YM, Rynditch AV, Vozianov AF. Hypermethylation of the 5'CpG island of the FHIT gene in clear cell renal carcinomas. Cancer Lett 2008, 265:250-257.
55. Morris MR, Hesson LB, Wagner KJ, Morgan NV, Astuti D, Lees RD, Cooper WN, Lee J, Gentle D, Macdonald F, Kishida T, Grundy R, Yao M, Latif F, Maher ER. Multigene methylation analysis of Wilms' tumour and adult renal cell carcinoma. Oncogene 2003, 22:6794-6801.
56. Vincan E. Frizzled/WNT signalling: the insidious promoter of tumour growth and progression. Front Biosci 2004, 9:1023-1034.
57. Widelitz R. Wnt signaling through canonical and non-canonical pathways: recent progress. Growth Factors 2005, 23:111-116.
58. Kawano Y, Kypta R. Secreted antagonists of the Wnt signalling pathway. J Cell Sci 2003, 116:2627-2634.
59. Niehrs C. Function and biological roles of the Dickkopf family of Wnt modulators. Oncogene 2006, 25:7469-7481.
60. Awakura Y, Nakamura E, Ito N, Kamoto T, Ogawa O. Methylation-associated silencing of SFRP1 in renal cell carcinoma. Oncol Rep 2008, 20:1257-1263.
61. Dahl E, Wiesmann F, Woenckhaus M, Stoehr R, Wild PJ, Veeck J, Knüchel R, Klopocki E, Sauter G, Simon R, Wieland WF, Walter B, Denzinger S, Hartmann A, Hammerschmied CG. Frequent loss of SFRP1 expression in multiple human solid tumours: association with aberrant promoter methylation in renal cell carcinoma. Oncogene 2007, 26:5680-5691.
62. Gumz ML, Zou H, Kreinest PA, Childs AC, Belmonte LS, LeGrand SN, Wu KJ, Luxon BA, Sinha M, Parker AS, Sun LZ, Ahlquist DA, Wood CG, Copland JA. Secreted frizzled-related protein 1 loss contributes to tumor phenotype of clear cell renal cell carcinoma. Clin Cancer Res 2007, 13:4740-4749.
63. Urakami S, Shiina H, Enokida H, Hirata H, Kawamoto K, Kawakami T, Kikuno N, Tanaka Y, Majid S, Nakagawa M, Igawa M, Dahiya R. Wnt antagonist family genes as biomarkers for diagnosis, staging, and prognosis of renal cell carcinoma using tumor and serum DNA. Clin Cancer Res 2006, 12:6989-6997.
64. Morris MR, Ricketts C, Gentle D, Abdulrahman M, Clarke N, Brown M, Kishida T, Yao M, Latif F, Maher ER. Identification of candidate tumour suppressor genes frequently methylated in renal cell carcinoma. Oncogene 2010, 29:2104-2117.
65. Hirata H, Hinoda Y, Nakajima K, Kawamoto K, Kikuno N, Kawakami K, Yamamura S, Ueno K, Majid S, Saini S, Ishii N, Dahiya R. Wnt antagonist gene DKK2 is epigenetically silenced and inhibits renal cancer progression through apoptotic and cell cycle pathways. Clin Cancer Res 2009, 15:5678-5687.
66. Hirata H, Hinoda Y, Nakajima K, Kawamoto K, Kikuno N, Ueno K, Yamamura S, Zaman MS, Khatri G, Chen Y, Saini S, Majid S, Deng G, Ishii N, Dahiya R. Wnt antagonist DKK1 acts as a tumor suppressor gene that induces apoptosis and inhibits proliferation in human renal cell carcinoma. Int J Cancer 2010,
67. Saini S, Liu J, Yamamura S, Majid S, Kawakami K, Hirata H, Dahiya R. Functional significance of secreted Frizzled-related protein 1 in metastatic renal cell carcinomas. Cancer Res 2009, 69:6815-6822.
68. Chen J, Lui W-O, Vos MD, Clark GJ, Takahashi M, Schoumans J, Khoo SK, Petillo D, Lavery T, Sugimura J, Astuti D, Zhang C, Kagawa S, Maher ER, Larsson C, Alberts AS, Kanayama HO, Teh BT. The t(1;3) breakpoint-spanning genes LSAMP and NORE1 are involved in clear cell renal cell carcinomas. Cancer Cell 2003, 4:405-413.
69. Schmidt L, Junker K, Nakaigawa N, Kinjerski T, Weirich G, Miller M, Lubensky I, Neumann HP, Brauch H, Decker J, Vocke C, Brown JA, Jenkins R, Richard S, Bergerheim U, Gerrard B, Dean M, Linehan WM, Zbar B. Novel mutations of the MET proto-oncogene in papillary renal carcinomas. Oncogene 1999, 18:2343-2350.
70. Schmidt L, Duh FM, Chen F, Kishida T, Glenn G, Choyke P, Scherer SW, Zhuang Z, Lubensky I, Dean M, Allikmets R, Chidambaram A, Bergerheim UR, Feltis JT, Casadevall C, Zamarron A, Bernues M, Richard S, Lips CJ, Walther MM, Tsui LC, Geil L, Orcutt ML, Stackhouse T, Lipan J, Slife L, Brauch H, Decker J, Niehans G, Hughson MD, et al. Germline and somatic mutations in the tyrosine kinase domain of the MET proto-oncogene in papillary renal carcinomas. Nat Genet 1997, 16:68-73.
71. Morris MR, Gentle D, Abdulrahman M, Maina EN, Gupta K, Banks RE, Wiesener MS, Kishida T, Yao M, Teh B, Latif F, Maher ER. 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 2005, 65:4598-4606.
72. Chitalia VC, Foy RL, Bachschmid MM, Zeng L, Panchenko MV, Zhou MI, Bharti A, Seldin DC, Lecker SH, Dominguez I, Cohen HT. Jade-1 inhibits Wnt signalling by ubiquitylating beta-catenin and mediates Wnt pathway inhibition by pVHL. Nat Cell Biol 2008, 10:1208-1216. 2830866, 18806787.
73. Zatyka M, da Silva NF, Clifford SC, Morris MR, Wiesener MS, Eckardt K-U, Houlston RS, Richards FM, Latif F, Maher ER. Identification of cyclin D1 and other novel targets for the von Hippel-Lindau tumor suppressor gene by expression array analysis and investigation of cyclin D1 genotype as a modifier in von Hippel-Lindau disease. Cancer Res 2002, 62:3803-3811.
74. Qi H, Ohh M. The von Hippel-Lindau tumor suppressor protein sensitizes renal cell carcinoma cells to tumor necrosis factor-induced cytotoxicity by suppressing the nuclear factor-kappaB-dependent antiapoptotic pathway. Cancer Res 2003, 63:7076-7080.
75. Genetos DC, Toupadakis CA, Raheja LF, Wong A, Papanicolaou SE, Fyhrie DP, Loots GG, Yellowley CE. Hypoxia decreases sclerostin expression and increases Wnt signaling in osteoblasts. J Cell Biochem 2010, 110:457-467. 2881162, 20336693.
76. Roe J-S, Youn H-D. The positive regulation of p53 by the tumor suppressor VHL. Cell Cycle 2006, 5:2054-2056.
77. Bishop T, Lau KW, Epstein ACR, Kim SK, Jiang M, O'Rourke D, Pugh CW, Gleadle JM, Taylor MS, Hodgkin J, Ratcliffe PJ. Genetic analysis of pathways regulated by the von Hippel-Lindau tumor suppressor in Caenorhabditis elegans. PLoS Biol 2004, 2:e289. 515368, 15361934.
78. Kajimura S, Aida K, Duan C. Understanding hypoxia-induced gene expression in early development: in vitro and in vivo analysis of hypoxia-inducible factor 1-regulated zebra fish insulin-like growth factor binding protein 1 gene expression. Mol Cell Biol 2006, 26:1142-1155. 1347021, 16428465.
79. Slomiany MG, Rosenzweig SA. IGF-1-induced VEGF and IGFBP-3 secretion correlates with increased HIF-1 alpha expression and activity in retinal pigment epithelial cell line D407. Invest Ophthalmol Vis Sci 2004, 45:2838-2847.
80. Yang S, Kim J, Ryu J-H, Oh H, Chun C-H, Kim BJ, Min BH, Chun J-S. Hypoxia-inducible factor-2alpha is a catabolic regulator of osteoarthritic cartilage destruction. Nat Med 2010, 16:687-693.
81. Dalgliesh GL, Furge K, Greenman C, Chen L, Bignell G, Butler A, Davies H, Edkins S, Hardy C, Latimer C, Teague J, Andrews J, Barthorpe S, Beare D, Buck G, Campbell PJ, Forbes S, Jia M, Jones D, Knott H, Kok CY, Lau KW, Leroy C, Lin ML, McBride DJ, Maddison M, Maguire S, McLay K, Menzies A, Mironenko T, et al. Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes. Nature 2010, 463:360-363. 2820242, 20054297.
82. Sanz-Casla MT, Maestro ML, del Barco V, Zanna I, Moreno J, Vidaurreta M, Almansa I, Fernández C, Blanco J, Maestro C, Resel L. Loss of heterozygosity and methylation of p16 in renal cell carcinoma. Urol Res 2003, 31:159-162.
83. Tong WG, Wierda WG, Lin E, Kuang SQ, Bekele BN, Estrov Z, Wei Y, Yang H, Keating MJ, Garcia-Manero G. Genome-wide DNA methylation profiling of chronic lymphocytic leukemia allows identification of epigenetically repressed molecular pathways with clinical impact. Epigenetics 2010, 5:499-508.
84. Boumber YA, Kondo Y, Chen X, Shen L, Gharibyan V, Konishi K, Estey E, Kantarjian H, Garcia-Manero G, Issa J-PJ. RIL, a LIM gene on 5q31, is silenced by methylation in cancer and sensitizes cancer cells to apoptosis. Cancer Res 2007, 67:1997-2005.
85. Tellez CS, Shen L, Estécio MRH, Jelinek J, Gershenwald JE, Issa J-PJ. CpG island methylation profiling in human melanoma cell lines. Melanoma Res 2009, 19:146-155.
86. Veena MS, Lee G, Keppler D, Mendonca MS, Redpath JL, Stanbridge EJ, Wilczynski SP, Srivatsan ES. Inactivation of the cystatin E/M tumor suppressor gene in cervical cancer. Genes Chromosomes Cancer 2008, 47:740-754.
87. Rivenbark AG, Livasy CA, Boyd CE, Keppler D, Coleman WB. Methylation-dependent silencing of CST6 in primary human breast tumors and metastatic lesions. Exp Mol Pathol 2007, 83:188-197. 2693953, 17540367.
88. Dallol A, Krex D, Hesson L, Eng C, Maher ER, Latif F. Frequent epigenetic inactivation of the SLIT2 gene in gliomas. Oncogene 2003, 22:4611-4616.
89. Dunwell TL, Dickinson RE, Stankovic T, Dallol A, Weston V, Austen B, Catchpoole D, Maher ER, Latif F. Frequent epigenetic inactivation of the SLIT2 gene in chronic and acute lymphocytic leukemia. Epigenetics 2009, 4:265-269.
90. Hanafusa T, Yumoto Y, Nouso K, Nakatsukasa H, Onishi T, Fujikawa T, Taniyama M, Nakamura S, Uemura M, Takuma Y, Yumoto E, Higashi T, Tsuji T. Reduced expression of insulin-like growth factor binding protein-3 and its promoter hypermethylation in human hepatocellular carcinoma. Cancer Lett 2002, 176:149-158.
91. Wiley A, Katsaros D, Fracchioli S, Yu H. Methylation of the insulin-like growth factor binding protein-3 gene and prognosis of epithelial ovarian cancer. Int J Gynecol Cancer 2006, 16:210-218.
92. Kongkham PN, Northcott PA, Ra YS, Nakahara Y, Mainprize TG, Croul SE, Smith CA, Taylor MD, Rutka JT. An epigenetic genome-wide screen identifies SPINT2 as a novel tumor suppressor gene in pediatric medulloblastoma. Cancer Res 2008, 68:9945-9953.
93. Tung EK-K, Wong C-M, Yau T-O, Lee JM-F, Ching Y-P, Ng IO-L. HAI-2 is epigenetically downregulated in human hepatocellular carcinoma, and its Kunitz domain type 1 is critical for anti-invasive functions. Int J Cancer 2009, 124:1811-1819.
94. Dong W, Chen X, Xie J, Sun P, Wu Y. Epigenetic inactivation and tumor suppressor activity of HAI-2/SPINT2 in gastric cancer. Int J Cancer 2010, 127:1526-1534.
95. Irizarry RA, Ladd-Acosta C, Wen B, Wu Z, Montano C, Onyango P, Cui H, Gabo K, Rongione M, Webster M, Ji H, Potash JB, Sabunciyan S, Feinberg AP. The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores. Nat Genet 2009, 41:178-186. 2729128, 19151715.
96. Weisenberger DJ, Siegmund KD, Campan M, Young J, Long TI, Faasse MA, Kang GH, Widschwendter M, Weener D, Buchanan D, Koh H, Simms L, Barker M, Leggett B, Levine J, Kim M, French AJ, Thibodeau SN, Jass J, Haile R, Laird PW. CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer. Nat Genet 2006, 38:787-793.
97. McRonald FE, Morris MR, Gentle D, Winchester L, Baban D, Ragoussis J, Clarke NW, Brown MD, Kishida T, Yao M, Latif F, Maher ER. CpG methylation profiling in VHL related and VHL unrelated renal cell carcinoma. Mol Cancer 2009, 8:31. 2698845, 19493342.
98. van Haaften G, Dalgliesh GL, Davies H, Chen L, Bignell G, Greenman C, Edkins S, Hardy C, O'Meara S, Teague J, Butler A, Hinton J, Latimer C, Andrews J, Barthorpe S, Beare D, Buck G, Campbell PJ, Cole J, Forbes S, Jia M, Jones D, Kok CY, Leroy C, Lin ML, McBride DJ, Maddison M, Maquire S, McLay K, Menzies A, et al. Somatic mutations of the histone H3K27 demethylase gene UTX in human cancer. Nat Genet 2009, 41:521-523. 2873835, 19330029.
99. Cairns P. Gene methylation and early detection of genitourinary cancer: the road ahead. Nat Rev Cancer 2007, 7:531-543.
100. Baylin SB, Herman JG, Graff JR, Vertino PM, Issa JP. Alterations in DNA methylation: a fundamental aspect of neoplasia. Adv Cancer Res 1998, 72:141-196.
101. Breault JE, Shiina H, Igawa M, Ribeiro-Filho LA, Deguchi M, Enokida H, Urakami S, Terashima M, Nakagawa M, Kane CJ, Carroll PR, Dahiya R. Methylation of the gamma-catenin gene is associated with poor prognosis of renal cell carcinoma. Clin Cancer Res 2005, 11:557-564.
102. van Vlodrop IJH, Baldewijns MML, Smits KM, Schouten LJ, van Neste L, Van Criekinge W, van Poppel H, Lerut E, Schuebel KE, Ahuja N, Herman JG, de Bruïne AP, van Engeland M. Prognostic significance of Gremlin1 (GREM1) promoter CpG island hypermethylation in clear cell renal cell carcinoma. Am J Pathol 2010, 176:575-584.
103. Okuda H, Toyota M, Ishida W, Furihata M, Tsuchiya M, Kamada M, Tokino T, Shuin T. Epigenetic inactivation of the candidate tumor suppressor gene HOXB13 in human renal cell carcinoma. Oncogene 2006, 25:1733-1742.
104. Silverman LR, Demakos EP, Peterson BL, Kornblith AB, Holland JC, Odchimar-Reissig R, Stone RM, Nelson D, Powell BL, DeCastro CM, Ellerton J, Larson RA, Schiffer CA, Holland JF. Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B. J Clin Oncol 2002, 20:2429-2440.
105. Oki Y, Jelinek J, Shen L, Kantarjian HM, Issa JP. Induction of hypomethylation and molecular response after decitabine therapy in patients with chronic myelomonocytic leukemia. Blood 2008, 111:2382-2384. 2234065, 18055864.
106. 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 2006, 66:5021-5028.
107. Christoph F, Weikert S, Kempkensteffen C, Krause H, Schostak M, Köllermann J, Miller K, Schrader M. Promoter hypermethylation profile of kidney cancer with new proapoptotic p53 target genes and clinical implications. Clin Cancer Res 2006, 12:5040-5046.
108. Majid S, Dar AA, Ahmad AE, Hirata H, Kawakami K, Shahryari V, Saini S, Tanaka Y, Dahiya AV, Khatri G, Dahiya R. BTG3 tumor suppressor gene promoter demethylation, histone modification and cell cycle arrest by genistein in renal cancer. Carcinogenesis 2009, 30:662-670. 2664457, 19221000.
109. Morris MR, Gentle D, Abdulrahman M, Clarke N, Brown M, Kishida T, Yao M, Teh BT, Latif F, Maher ER. Functional epigenomics approach to identify methylated candidate tumour suppressor genes in renal cell carcinoma. Br J Cancer 2008, 98:496-501. 2361461, 18195710.
110. Yamada D, Kikuchi S, Williams YN, Sakurai-Yageta M, Masuda M, Maruyama T, Tomita K, Gutmann DH, Kakizoe T, Kitamura T, Kanai Y, Murakami Y. Promoter hypermethylation of the potential tumor suppressor DAL-1/4.1B gene in renal clear cell carcinoma. Int J Cancer 2006, 118:916-923.
111. Christoph F, Kempkensteffen C, Weikert S, Köllermann J, Krause H, Miller K, Schostak M, Schrader M. 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, 95:1701-1707. 2360762, 17133271.
112. Zhang Q, Ying J, Zhang K, Li H, Ng KM, Zhao Y, He Q, Yang X, Xin D, Liao S-K, Tao Q, Jin J. Aberrant methylation of the 8p22 tumor suppressor gene DLC1 in renal cell carcinoma. Cancer Lett 2007, 249:220-226.
113. Khoo SK, Kahnoski K, Sugimura J, Petillo D, Chen J, Shockley K, Ludlow J, Knapp R, Giraud S, Richard S, Nordenskjöld M, Teh BT. Inactivation of BHD in sporadic renal tumors. Cancer Res 2003, 63:4583-4587.
114. da Silva NF, Gentle D, Hesson LB, Morton DG, Latif F, Maher ER. Analysis of the Birt-Hogg-Dubé (BHD) tumour suppressor gene in sporadic renal cell carcinoma and colorectal cancer. J Med Genet 2003, 40:820-824. 1735328, 14627671.
115. Gad S, Lefèvre SH, Khoo SK, Giraud S, Vieillefond A, Vasiliu V, Ferlicot S, Molinié V, Denoux Y, Thiounn N, Chrétien Y, Méjean A, Zerbib M, Benoît G, Hervé JM, Allègre G, Bressac-de Paillerets B, Teh BT, Richard S. Mutations in BHD and TP53 genes, but not in HNF1beta gene, in a large series of sporadic chromophobe renal cell carcinoma. Br J Cancer 2007, 96:336-340. 2360004, 17133269.
116. 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 2009, 7:90. 2775027, 19857250.
117. Dallol A, Forgacs E, Martinez A, Sekido Y, Walker R, Kishida T, Rabbitts P, Maher ER, Minna JD, Latif F. Tumour specific promoter region methylation of the human homologue of the Drosophila Roundabout gene DUTT1 (ROBO1) in human cancers. Oncogene 2002, 21:3020-3028.
118. Astuti D, Da Silva NF, Dallol A, Gentle D, Martinsson T, Kogner P, Grundy R, Kishida T, Yao M, Latif F, Maher ER. SLIT2 promoter methylation analysis in neuroblastoma, Wilms' tumour and renal cell carcinoma. Br J Cancer 2004, 90:515-521. 2409544, 14735202.
119. Bachman KE, Herman JG, Corn PG, Merlo A, Costello JF, Cavenee WK, Baylin SB, Graff JR. Methylation-associated silencing of the tissue inhibitor of metalloproteinase-3 gene suggest a suppressor role in kidney, brain, and other human cancers. Cancer Res 1999, 59:798-802.
120. Kempkensteffen C, Hinz S, Schrader M, Christoph F, Magheli A, Krause H, Schostak M, Miller K, Weikert S. Gene expression and promoter methylation of the XIAP-associated Factor 1 in renal cell carcinomas: correlations with pathology and outcome. Cancer Lett 2007, 254:227-235.
121. Lee M-G, Huh J-S, Chung S-K, Lee J-H, Byun D-S, Ryu B-K, Kang M-J, Chae K-S, Lee S-J, Lee C-H, Kim JI, Chang SG, Chi SG. Promoter CpG hypermethylation and downregulation of XAF1 expression in human urogenital malignancies: implication for attenuated p53 response to apoptotic stresses. Oncogene 2006, 25:5807-5822.