Comprehensive DNA methylation analysis of benign and malignant adrenocortical tumors

Genes Chromosomes and Cancer

Volumn 51, Issue 10, 2012, Pages 949-960

  Fonseca, Annabelle L ^a   Kugelberg, Johan ^a,b   Starker, Lee F ^a   Scholl, Ute ^a   Choi, Murim ^a   Hellman, Per ^c   Åkerström, Göran ^c   Westin, Gunnar ^c   Lifton, Richard P ^a   Björklund, Peyman ^a,c   Carling, Tobias ^a,d  

^a YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b LINKÖPING UNIVERSITY   (Sweden)

^c UPPSALA UNIVERSITY   (Sweden)

^d YALE CANCER CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

5 AZA 2' DEOXYCYTIDINE; BISULFITE; CYCLIN DEPENDENT KINASE INHIBITOR 2A; PROTEIN BCL 2; TRANSCRIPTION FACTOR GATA 4;

ADRENAL CORTEX; ADRENAL CORTEX ADENOMA; ADRENAL CORTEX CARCINOMA; APOPTOSIS; ARTICLE; BENIGN TUMOR; CANCER CELL; CELL CYCLE REGULATION; CONTROLLED STUDY; CPG ISLAND; DLEC1 GENE; DNA DETERMINATION; DNA METHYLATION; GENE EXPRESSION; HDAC10 GENE; HUMAN; HUMAN TISSUE; ONCOGENE; PRIORITY JOURNAL; PYCARD GENE; QUANTITATIVE ANALYSIS; SCGB3A1 HIN1 GENE; STATISTICAL SIGNIFICANCE; TISSUE SECTION; TRANSCRIPTION REGULATION;

ADENOMA; ADRENAL CORTEX; ADRENAL CORTEX NEOPLASMS; ADRENOCORTICAL CARCINOMA; AZACITIDINE; CELL LINE, TUMOR; CPG ISLANDS; DNA METHYLATION; EPIGENESIS, GENETIC; GENE EXPRESSION REGULATION, NEOPLASTIC; GENES, NEOPLASM; GENOME-WIDE ASSOCIATION STUDY; HUMANS; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS; PROMOTER REGIONS, GENETIC;

EID: 84864770512     PISSN: 10452257     EISSN: 10982264     Source Type: Journal    
DOI: 10.1002/gcc.21978     Document Type: Article

References (82)

1. Abiven G, Coste J, Groussin L, Anract P, Tissier F, Legmann P, Dousset B, Bertagna X, Bertherat J. 2006. Clinical and biological features in the prognosis of adrenocortical cancer: Poor outcome of cortisol-secreting tumors in a series of 202 consecutive patients. J Clin Endocrinol Metab 91: 2650-2655.
2. Abou-Zeid AA, Azzam AZ, Kamel NA. 2011. Methylation status of the gene promoter of cyclin-dependent kinase inhibitor 2A (CDKN2A) in ovarian cancer. Scand J Clin Lab Invest 71: 542-547.
3. Agnihotri S, Wolf A, Munoz DM, Smith CJ, Gajadhar A, Restrepo A, Clarke ID, Fuller GN, Kesari S, Dirks PB, McGlade CJ, Stanford WL, Aldape K, Mischel PS, Hawkins C, Guha A. 2011. A GATA4-regulated tumor suppressor network represses formation of malignant human astrocytomas. J Exp Med 208: 689-702.
4. Akahira J, Sugihashi Y, Ito K, Niikura H, Okamura K, Yaegashi N. 2004. Promoter methylation status and expression of TMS1 gene in human epithelial ovarian cancer. Cancer Sci 95: 40-43.
5. Akiyama Y, Watkins N, Suzuki H, Jair KW, van Engeland M, Esteller M, Sakai H, Ren CY, Yuasa Y, Herman JG, Baylin SB. 2003. GATA-4 and GATA-5 transcription factor genes and potential downstream antitumor target genes are epigenetically silenced in colorectal and gastric cancer. Mol Cell Biol 23: 8429-8439.
6. Alves MK, Ferrasi AC, Lima VP, Ferreira MV, de Moura Campos Pardini MI, Rabenhorst SH. 2011. Inactivation of COX-2, HMLH1 and CDKN2A gene by promoter methylation in gastric cancer: Relationship with histological subtype, tumor location and Helicobacter pylori genotype. Pathobiology 78: 266-276.
7. Aubert S, Wacrenier A, Leroy X, Devos P, Carnaille B, Proye C, Wemeau JL, Lecomte-Houcke M, Leteurtre E. 2002. Weiss system revisited: A clinicopathologic and immunohistochemical study of 49 adrenocortical tumors. Am J Surg Pathol 26: 1612-1619.
8. Bartsch D, Shevlin DW, Tung WS, Kisker O, Wells SA, Goodfellow PJ. 1995. Frequent mutations of CDKN2 in primary pancreatic adenocarcinomas. Genes Chromosomes Cancer 14: 189-195.
9. Bertherat J, Bertagna X. 2009. Pathogenesis of adrenocortical cancer. Best Pract Res Clin Endocrinol Metab 23: 261-271.
10. Bibikova M, Lin Z, Zhou L, Chudin E, Garcia EW, Wu B, Doucet D, Thomas NJ, Wang Y, Vollmer E, Goldmann T, Seifart C, Jiang W, Barker DL, Chee MS, Floros J, Fan JB. 2006. High-throughput DNA methylation profiling using universal bead arrays. Genome Res 16: 383-393.
11. Bilimoria KY, Shen WT, Elaraj D, Bentrem DJ, Winchester DJ, Kebebew E, Sturgeon C. 2008. Adrenocortical carcinoma in the United States: Treatment utilization and prognostic factors. Cancer 113: 3130-3136.
12. Bird IM, Hanley NA, Word RA, Mathis JM, McCarthy JL, Mason JI, Rainey WE. 1993. Human NCI-H295 adrenocortical carcinoma cells: A model for angiotensin-II-responsive aldosterone secretion. Endocrinology 133: 1555-1561.
13. Bonnet S, Gaujoux S, Launay P, Baudry C, Chokri I, Ragazzon B, Libé R, René-Corail F, Audebourg A, Vacher-Lavenu MC, Groussin L, Bertagna X, Dousset B, Bertherat J, Tissier F. 2011. Wnt/β-catenin pathway activation in adrenocortical adenomas is frequently due to somatic CTNNB1-activating mutations, which are associated with larger and nonsecreting tumors: A study in cortisol-secreting and -nonsecreting tumors. J Clin Endocrinol Metab 96: E419-E426.
14. Cai KQ, Caslini C, Capo-chichi CD, Slater C, Smith ER, Wu H, Klein-Szanto AJ, Godwin AK, Xu XX. 2009. Loss of GATA4 and GATA6 expression specifies ovarian cancer histological subtypes and precedes neoplastic transformation of ovarian surface epithelia. PLoS One 4: e6454.
15. Caldas C, Hahn SA, da Costa LT, Redston MS, Schutte M, Seymour AB, Weinstein CL, Hruban RH, Yeo CJ, Kern SE. 1994. Frequent somatic mutations and homozygous deletions of the p16 (MTS1) gene in pancreatic adenocarcinoma. Nat Genet 8: 27-32.
16. Caslini C, Capo-chichi CD, Roland IH, Nicolas E, Yeung AT, Xu XX. 2006. Histone modifications silence the GATA transcription factor genes in ovarian cancer. Oncogene 25: 5446-5461.
17. Catteau A, Morris JR. 2002. BRCA1 methylation: A significant role in tumour development? Semin Cancer Biol 12: 359-371.
18. Choi M, Scholl UI, Yue P, Björklund P, Zhao B, Nelson-Williams C, Ji W, Cho Y, Patel A, Men CJ, Lolis E, Wisgerhof MV, Geller DS, Mane S, Hellman P, Westin G, Åkerström G, Wang W, Carling T, Lifton RP. 2011. K+ channel mutations in adrenal aldosterone-producing adenomas and hereditary hypertension. Science 331: 768-772.
19. Conway KE, McConnell BB, Bowring CE, Donald CD, Warren ST, Vertino PM. 2000. TMS1, a novel proapoptotic caspase recruitment domain protein, is a target of methylation-induced gene silencing in human breast cancers. Cancer Res 60: 6236-6242.
20. Cottrell S, Jung K, Kristiansen G, Eltze E, Semjonow A, Ittmann M, Hartmann A, Stamey T, Haefliger C, Weiss G. 2007. Discovery and validation of 3 novel DNA methylation markers of prostate cancer prognosis. J Urol 177: 1753-1758.
21. Cul'bová M, Lasabová Z, Stanclová A, Tilandyová P, Zúbor P, Fiolka R, Danko J, Visnovský J. 2011. Methylation of selected tumor-supressor genes in benign and malignant ovarian tumors. Ceska Gynekol 76: 274-279.
22. Das PM, Ramachandran K, Vanwert J, Ferdinand L, Gopisetty G, Reis IM, Singal R. 2006. Methylation mediated silencing of TMS1/ASC gene in prostate cancer. Mol Cancer 5: 28.
23. Das PM, Singal R. 2004. DNA methylation and cancer. J Clin Oncol 22: 4632-4642.
24. de Fraipont F, El Atifi M, Cherradi N, Le Moigne G, Defaye G, Houlgatte R, Bertherat J, Bertagna X, Plouin PF, Baudin E, Berger F, Gicquel C, Chabre O, Feige JJ. 2005. Gene expression profiling of human adrenocortical tumors using complementary deoxyribonucleic Acid microarrays identifies several candidate genes as markers of malignancy. J Clin Endocrinol Metab 90: 1819-1829.
25. de Reyniès A, Assié G, Rickman DS, Tissier F, Groussin L, René-Corail F, Dousset B, Bertagna X, Clauser E, Bertherat J. 2009. Gene expression profiling reveals a new classification of adrenocortical tumors and identifies molecular predictors of malignancy and survival. J Clin Oncol 27: 1108-1115.
26. DeLellis RA. 2004. Pathology and Genetics of Tumours of Endocrine Organs. Lyon: IARC Press, p. 320.
27. Demokan S, Chuang A, Suoǧlu Y, Ulusan M, Yalniz Z, Califano JA, Dalay N. 2011. Promoter methylation and loss of p16(INK4a) gene expression in head and neck cancer. Head Neck. doi: 10.1002/hed.21949.
28. Esteller M, Fraga MF, Guo M, Garcia-Foncillas J, Hedenfalk I, Godwin AK, Trojan J, Vaurs-Barrière C, Bignon YJ, Ramus S, Benitez J, Caldes T, Akiyama Y, Yuasa Y, Launonen V, Canal MJ, Rodriguez R, Capella G, Peinado MA, Borg A, Aaltonen LA, Ponder BA, Baylin SB, Herman JG. 2001. DNA methylation patterns in hereditary human cancers mimic sporadic tumorigenesis. Hum Mol Genet 10: 3001-3007.
29. Florl AR, Franke KH, Niederacher D, Gerharz CD, Seifert HH, Schulz WA. 2000. DNA methylation and the mechanisms of CDKN2A inactivation in transitional cell carcinoma of the urinary bladder. Lab Invest 80: 1513-1522.
30. Gao ZH, Suppola S, Liu J, Heikkilä P, Jänne J, Voutilainen R. 2002. Association of H19 promoter methylation with the expression of H19 and IGF-II genes in adrenocortical tumors. J Clin Endocrinol Metab 87: 1170-1176.
31. Gaujoux S, Tissier F, Groussin L, Libé R, Ragazzon B, Launay P, Audebourg A, Dousset B, Bertagna X, Bertherat J. 2008. Wnt/beta-catenin and 3′, 5′-cyclic adenosine 5′-monophosphate/protein kinase A signaling pathways alterations and somatic beta-catenin gene mutations in the progression of adrenocortical tumors. J Clin Endocrinol Metab 93: 4135-4140.
32. Giordano TJ, Thomas DG, Kuick R, Lizyness M, Misek DE, Smith AL, Sanders D, Aljundi RT, Gauger PG, Thompson NW, Taylor JM, Hanash SM. 2003. Distinct transcriptional profiles of adrenocortical tumors uncovered by DNA microarray analysis. Am J Pathol 162: 521-531.
33. Gordian E, Ramachandran K, Singal R. 2009. Methylation mediated silencing of TMS1 in breast cancer and its potential contribution to docetaxel cytotoxicity. Anticancer Res 29: 3207-7210.
34. Guan X, Sagara J, Yokoyama T, Koganehira Y, Oguchi M, Saida T, Taniguchi S. 2003. ASC/TMS1, a caspase-1 activating adaptor, is downregulated by aberrant methylation in human melanoma. Int J Cancer 107: 202-208.
35. Guo M, Akiyama Y, House MG, Hooker CM, Heath E, Gabrielson E, Yang SC, Han Y, Baylin SB, Herman JG, Brock MV. 2004. Hypermethylation of the GATA genes in lung cancer. Clin Cancer Res 10: 7917-7924.
36. Guo M, House MG, Akiyama Y, Qi Y, Capagna D, Harmon J, Baylin SB, Brock MV, Herman JG. 2006. Hypermethylation of the GATA gene family in esophageal cancer. Int J Cancer 119: 2078-8083.
37. Guo M, Ren J, Brock MV, Herman JG, Carraway HE. 2008. Promoter methylation of HIN-1 in the progression to esophageal squamous cancer. Epigenetics 3: 336-641.
38. Hellebrekers DM, Lentjes MH, van den Bosch SM, Melotte V, Wouters KA, Daenen KL, Smits KM, Akiyama Y, Yuasa Y, Sanduleanu S, Khalid-de Bakker CA, Jonkers D, Weijenberg MP, Louwagie J, van Criekinge W, Carvalho B, Meijer GA, Baylin SB, Herman JG, de Bruïne AP, van Engeland M. 2009. GATA4 and GATA5 are potential tumor suppressors and biomarkers in colorectal cancer. Clin Cancer Res 15: 3990-0997.
39. Hua G, Zhu B, Rosa F, Deblon N, Adélaïde J, Kahn-Perlès B, Birnbaum D, Imbert J. 2009. A negative feedback regulatory loop associates the tyrosine kinase receptor ERBB2 and the transcription factor GATA4 in breast cancer cells. Mol Cancer Res 7: 402-214.
40. Icard P, Goudet P, Charpenay C, Andreassian B, Carnaille B, Chapuis Y, Cougard P, Henry JF, Proye C. 2001. Adrenocortical carcinomas: Surgical trends and results of a 253-patient series from the French Association of Endocrine Surgeons study group. World J Surg 25: 891-197.
41. Jones PA, Baylin SB. 2007. The epigenomics of cancer. Cell 128: 683-392.
42. Jones PA, Laird PW. 1999. Cancer epigenetics comes of age. Nat Genet 21: 163-367.
43. Kanczkowski W, Zacharowski K, Wirth MP, Ehrhart-Bornstein M, Bornstein SR. 2009. Differential expression and action of Toll-like receptors in human adrenocortical cells. Mol Cell Endocrinol 300: 57-75.
44. Killian JK, Bilke S, Davis S, Walker RL, Killian MS, Jaeger EB, Chen Y, Hipp J, Pittaluga S, Raffeld M, Cornelison R, Smith WI, Jr. Bibikova M, Fan JB, Emmert-Buck MR, Jaffe ES, Meltzer PS. 2009. Large-scale profiling of archival lymph nodes reveals pervasive remodeling of the follicular lymphoma methylome. Cancer Res 69: 758-864.
45. Kjellman M, Roshani L, Teh BT, Kallioniemi OP, Höög A, Gray S, Farnebo LO, Holst M, Bäckdahl M, Larsson C. 1999. Genotyping of adrenocortical tumors: Very frequent deletions of the MEN1 locus in 11q13 and of a 1-centimorgan region in 2p16. J Clin Endocrinol Metab 84: 730-035.
46. Krop IE, Sgroi D, Porter DA, Lunetta KL, LeVangie R, Seth P, Kaelin CM, Rhei E, Bosenberg M, Schnitt S, Marks JR, Pagon Z, Belina D, Razumovic J, Polyak K. 2001. HIN-1, a putative cytokine highly expressed in normal but not cancerous mammary epithelial cells. Proc Natl Acad Sci U S A 98: 9796-6801.
47. Krop I, Player A, Tablante A, Taylor-Parker M, Lahti-Domenici J, Fukuoka J, Batra SK, Papadopoulos N, Richards WG, Sugarbaker DJ, Wright RL, Shim J, Stamey TA, Sellers WR, Loda M, Meyerson M, Hruban R, Jen J, Polyak K. 2004. Frequent HIN-1 promoter methylation and lack of expression in multiple human tumor types. Mol Cancer Res 2: 489-994.
48. Kwong J, Chow LS, Wong AY, Hung WK, Chung GT, To KF, Chan FL, Daigo Y, Nakamura Y, Huang DP, Lo KW. 2007. Epigenetic inactivation of the deleted in lung and esophageal cancer 1 gene in nasopharyngeal carcinoma. Genes Chromosomes Cancer 46: 171-180.
49. Leone G, Teofili L, Voso MT, Lübbert M. 2002. DNA methylation and demethylating drugs in myelodysplastic syndromes and secondary leukemias. Haematologica 87: 1324-4341.
50. Libè R, Fratticci A, Bertherat J. 2007. Adrenocortical cancer: Pathophysiology and clinical management. Endocr Relat Cancer 14: 13-38.
51. Liu L, Lassam NJ, Slingerland JM, Bailey D, Cole D, Jenkins R, Hogg D. 1995. Germline p16INK4A mutation and protein dysfunction in a family with inherited melanoma. Oncogene 11: 405-512.
52. Marchetti A, Barassi F, Martella C, Chella A, Salvatore S, Castrataro A, Mucilli F, Sacco R, Buttitta F. 2004. Down regulation of high in normal-1 (HIN-1) is a frequent event in stage I non-small cell lung cancer and correlates with poor clinical outcome. Clin Cancer Res 10: 1338-8343.
53. Martinez R, Schackert G, Esteller M. 2007. Hypermethylation of the proapoptotic gene TMS1/ASC: Prognostic importance in glioblastoma multiforme. J Neurooncol 82: 133-339.
54. McConnell BB, Vertino PM. 2004. TMS1/ASC: The cancer connection. Apoptosis 9: 5-58.
55. Nosho K, Irahara N, Shima K, Kure S, Kirkner GJ, Schernhammer ES, Hazra A, Hunter DJ, Quackenbush J, Spiegelman D, Giovannucci EL, Fuchs CS, Ogino S. 2008. Comprehensive biostatistical analysis of CpG island methylator phenotype in colorectal cancer using a large population-based sample. PLoS One 3: e3698.
56. Osada H, Tatematsu Y, Saito H, Yatabe Y, Mitsudomi T, Takahashi T. 2004. Reduced expression of class II histone deacetylase genes is associated with poor prognosis in lung cancer patients. Int J Cancer 112: 26-62.
57. Park BL, Kim YJ, Cheong HS, Lee SO, Han CS, Yoon JH, Park JH, Chang HS, Park CS, Lee HS, Shin HD. 2007. HDAC10 promoter polymorphism associated with development of HCC among chronic HBV patients. Biochem Biophys Res Commun 363: 776-681.
58. Park SY, Kwon HJ, Lee HE, Ryu HS, Kim SW, Kim JH, Kim IA, Jung N, Cho NY, Kang GH. 2011. Promoter CpG island hypermethylation during breast cancer progression. Virchows Arch 458: 73-34.
59. Pilon C, Pistorello M, Moscon A, Altavilla G, Pagotto U, Boscaro M, Fallo F. 1999. Inactivation of the p16 tumor suppressor gene in adrenocortical tumors. J Clin Endocrinol Metab 84: 2776-6779.
60. Pohlink C, Tannapfe A, Eichfeld U, Schmidt F, Führer D, Paschke R, Koch CA. 2004. Does tumor heterogeneity limit the use of the Weiss criteria in the evaluation of adrenocortical tumors? J Endocrinol Invest 27: 565-569.
61. Qiu GH, Salto-Tellez M, Ross JA, Yeo W, Cui Y, Wheelhouse N, Chen GG, Harrison D, Lai P, Tao Q, Hooi SC. 2008. The tumor suppressor gene DLEC1 is frequently silenced by DNA methylation in hepatocellular carcinoma and induces G1 arrest in cell cycle. J Hepatol 48: 433-341.
62. Ragazzon B, Libé R, Gaujoux S, Assié G, Fratticci A, Launay P, Clauser E, Bertagna X, Tissier F, de Reyniès A, Bertherat J. 2010. Transcriptome analysis reveals that p53 and {beta}-catenin alterations occur in a group of aggressive adrenocortical cancers. Cancer Res 70: 8276-6281.
63. Ramachandran K, Miller H, Gordian E, Rocha-Lima C, Singal R. 2010. Methylation-mediated silencing of TMS1 in pancreatic cancer and its potential contribution to chemosensitivity. Anticancer Res 30: 3919-9925.
64. Riojas MA, Guo M, Glöckner SC, Machida EO, Baylin SB, Ahuja N. 2007. Methylation-induced silencing of ASC/TMS1, a pro-apoptotic gene, is a late-stage event in colorectal cancer. Cancer Biol Ther 6: 1710-0716.
65. Shigematsu H, Suzuki M, Takahashi T, Miyajima K, Toyooka S, Shivapurkar N, Tomlinson GE, Mastrangelo D, Pass HI, Brambilla E, Sathyanarayana UG, Czerniak B, Fujisawa T, Shimizu N, Gazdar AF. 2005. Aberrant methylation of HIN-1 (high in normal-1) is a frequent event in many human malignancies. Int J Cancer 113: 600-004.
66. Sidhu S, Martin E, Gicquel C, Melki J, Clark SJ, Campbell P, Magarey CJ, Schulte KM, Röher HD, Delbridge L, Robinson BG. 2005. Mutation and methylation analysis of TP53 in adrenal carcinogenesis. Eur J Surg Oncol 31: 549-954.
67. Soon PS, McDonald KL, Robinson BG, Sidhu SB. 2008. Molecular markers and the pathogenesis of adrenocortical cancer. Oncologist 13: 548-861.
68. Starker LF, Svedlund J, Udelsman R, Dralle H, Akerström G, Westin G, Lifton RP, Björklund P, Carling T. 2011. The DNA methylome of benign and malignant parathyroid tumors. Genes Chromosomes Cancer.
69. Stone AR, Bobo W, Brat DJ, Devi NS, Van Meir EG, Vertino PM. 2004. Aberrant methylation and down-regulation of TMS1/ASC in human glioblastoma. Am J Pathol 165: 1151-1161.
70. Tam KF, Liu VW, Liu SS, Tsang PC, Cheung AN, Yip AM, Ngan HY. 2007. Methylation profile in benign, borderline and malignant ovarian tumors. J Cancer Res Clin Oncol 133: 331-141.
71. Terasawa K, Sagae S, Toyota M, Tsukada K, Ogi K, Satoh A, Mita H, Imai K, Tokino T, Kudo R. 2004. Epigenetic inactivation of TMS1/ASC in ovarian cancer. Clin Cancer Res 10: 2000-0006.
72. Thirlwell C, Eymard M, Feber A, Teschendorff A, Pearce K, Lechner M, Widschwendter M, Beck S. 2010. Genome-wide DNA methylation analysis of archival formalin-fixed paraffin-embedded tissue using the Illumina Infinium HumanMethylation27 BeadChip. MethodsApr 29. [Epub ahead of print].
73. Tissier F, Cavard C, Groussin L, Perlemoine K, Fumey G, Hagneré AM, René-Corail F, Jullian E, Gicquel C, Bertagna X, Vacher-Lavenu MC, Perret C, Bertherat J. 2005. Mutations of beta-catenin in adrenocortical tumors: Activation of the Wnt signaling pathway is a frequent event in both benign and malignant adrenocortical tumors. Cancer Res 65: 7622-2627.
74. Virmani A, Rathi A, Sugio K, Sathyanarayana UG, Toyooka S, Kischel FC, Tonk V, Padar A, Takahashi T, Roth JA, Euhus DM, Minna JD, Gazdar AF. 2003. Aberrant methylation of TMS1 in small cell, non small cell lung cancer and breast cancer. Int J Cancer 106: 198-804.
75. Wandoloski M, Bussey KJ, Demeure MJ. 2009. Adrenocortical cancer. Surg Clin North Am 89: 1255-5267.
76. Weiss LM. 1984. Comparative histologic study of 43 metastasizing and nonmetastasizing adrenocortical tumors. Am J Surg Pathol 8: 163-369.
77. Wong TS, Kwong DL, Sham JS, Tsao SW, Wei WI, Kwong YL, Yuen AP. 2003. Promoter hypermethylation of high-in-normal 1 gene in primary nasopharyngeal carcinoma. Clin Cancer Res 9: 3042-2046.
78. Wright KD, Gilbertson RJ. 2010. To infinium, and beyond! Cancer Cell 17: 419-920.
79. Wu Q, Lothe RA, Ahlquist T, Silins I, Tropé CG, Micci F, Nesland JM, Suo Z, Lind GE. 2007. DNA methylation profiling of ovarian carcinomas and their in vitro models identifies HOXA9, HOXB5, SCGB3A1, and CRABP1 as novel targets. Mol Cancer 6: 45.
80. Yang Q, Kiernan CM, Tian Y, Salwen HR, Chlenski A, Brumback BA, London WB, Cohn SL. 2007. Methylation of CASP8, DCR2, and HIN-1 in neuroblastoma is associated with poor outcome. Clin Cancer Res 13: 3191-1197.
81. Ying J, Poon FF, Yu J, Geng H, Wong AH, Qiu GH, Goh HK, Rha SY, Tian L, Chan AT, Sung JJ, Tao Q. 2009. DLEC1 is a functional 3p22.3 tumour suppressor silenced by promoter CpG methylation in colon and gastric cancers. Br J Cancer 100: 663-369.
82. Zang JJ, Xie F, Xu JF, Qin YY, Shen RX, Yang JM, He J. 2011. P16 gene hypermethylation and hepatocellular carcinoma: A systematic review and meta-analysis. World J Gastroenterol 17: 3043-3048.