Global DNA hypomethylation in cancer: Review of validated methods and clinical significance

Clinical Chemistry and Laboratory Medicine

Volumn 50, Issue 10, 2012, Pages 1733-1742

  Toraño, Estela G ^a   Petrus, Sandra ^a   Fernandez, Agustin F ^a   Fraga, Mario F ^a,b  

^a DEPARTAMENTO DE BIOQUÍMICA Y BIOLOGÍA MOLECULAR   (Spain)

^b CENTRO NACIONAL DE BIOTECNOLOGÍA   (Spain)

Author keywords

Biomarkers; Cancer; DNA methylation; Hypomethylation

Indexed keywords

BIOLOGICAL MARKER;

CAPILLARY ELECTROPHORESIS; CARCINOGENESIS; CLINICAL ASSESSMENT; DIAGNOSTIC VALUE; DNA METHYLATION; DNA SEQUENCE; GENE LOCUS; GENE TECHNOLOGY; GENETIC ASSOCIATION; HIGH THROUGHPUT SEQUENCING; HUMAN; IMMUNOCHEMISTRY; IMMUNOPRECIPITATION; MALIGNANT NEOPLASTIC DISEASE; NONHUMAN; PRIORITY JOURNAL; PYROSEQUENCING; REPRODUCIBILITY; REVERSED PHASE HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; REVIEW; SENSITIVITY AND SPECIFICITY;

ANIMALS; DNA METHYLATION; EPIGENOMICS; GENETIC LOCI; HUMANS; NEOPLASMS; REPRODUCIBILITY OF RESULTS;

EID: 84867819173     PISSN: 14346621     EISSN: 14374331     Source Type: Journal    
DOI: 10.1515/cclm-2011-0902     Document Type: Review

References (110)

1. Waddington CH. The epigenotype. Endeavour 1942;1:18-20.
2. Berger SL, Kouzarides T, Shiekhattar R, Shilatifard A. An operational definition of epigenetics. Genes Dev 2009;23:781-3.
3. Wesley H, Brooks CL, Pers J-O, Youinou P, Renaudineau Y. Epigenetics and autoimmunity. J Autoimmun 2010;34:J207-19.
4. Esteller M. Epigenetics in cancer. N Engl J Med 2008;358:1148-59.
5. Jones PA, Baylin SB. The epigenomics of cancer. Cell 2007;128:683-92.
6. Bernstein BE, Meissner A, Lander ES. The mammalian epigenome. Cell 2007;128:669-81.
7. Ellis L, Atadja PW, Johnstone RW. Epigenetics in cancer: targeting chromatin modifications. Mol Cancer Ther 2009;8:1409-20.
8. Lujambio A, Portela A, Liz J, Melo SA, Rossi S, Spizzo R, et al. CpG island hypermethylation-associated silencing of non-coding RNAs transcribed from ultraconserved regions in human cancer. Oncogene 2010;29:6390-401.
9. Esteller M. Cancer epigenomics: DNA methylomes and histonemodification maps. Nat Rev Genet 2007;8:286-98.
10. Stancheva I, Meehan RR. Transient depletion of xDnmt1 leads to premature gene activation in Xenopus embryos. Genes Dev 2000;14:313-27.
11. Beard C, Li E, Jaenisch R. Loss of methylation activates Xist in somatic but not in embryonic cells. Genes Dev 1995;9:2325-34.
12. Walsh CP, Chaillet JR, Bestor TH. Transcription of IAP endogenous retroviruses is constrained by cytosine methylation. Nat Genet 1998;20:116-7.
13. Li E, Beard C, Jaenisch R. Role for DNA methylation in genomic imprinting. Nature 1993;366:362-5.
14. Haaf T, Schmid M. Experimental condensation inhibition in constitutive and facultative heterochromatin of mammalian chromosomes. Cytogenet Cell Genet 2000;91:113-23.
15. Denis H, Ndlovu MN, Fuks F. Regulation of mammalian DNA methyltransferases: a route to new mechanisms. EMBO Rep 2011;12:647-56.
16. Robertson KD. DNA methylation, methyltransferases, and cancer. Oncogene 2001;20:3139-55.
17. Bird A. DNA methylation patterns and epigenetic memory. Genes Dev 2002;16:6-21.
18. Wang Y, Leung FC. An evaluation of new criteria for CpG islands in the human genome as gene markers. Bioinformatics 2004;20:1170-7.
19. Suzuki MM, Bird A. DNA methylation landscapes: provocative insights from epigenomics. Nat Rev Genet 2008;9:465-76.
20. Goll MG, Bestor TH. Eukaryotic cytosine methyltransferases. Annu Rev Biochem 2005;74:481-514.
21. 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 2012;22:407-19.
22. Issa JP. The epigenetics of colorectal cancer. Ann N Y Acad Sci 2000;910:140-53; discussion 53-5.
23. Feinberg AP, Vogelstein B. Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature 1983;301:89-92.
24. Gama-Sosa MA, Slagel VA, Trewyn RW, Oxenhandler R, Kuo KC, Gehrke CW, et al. The 5-methylcytosine content of DNA from human tumors. Nucleic Acids Res 1983;11:6883-94.
25. Feinberg AP. Cancer epigenetics is no Mickey Mouse. Cancer Cell 2005;8:267-8.
26. Esteller M. The necessity of a human epigenome project. Carcinogenesis 2006;27:1121-5.
27. Herman JG. Hypermethylation of tumor suppressor genes in cancer. Semin Cancer Biol 1999;9:359-67.
28. Esteller M, Corn PG, Baylin SB, Herman JG. A gene hypermethylation profile of human cancer. Cancer Res 2001;61:3225-9.
29. Ehrlich M. Cancer-linked DNA hypomethylation and its relationship to hypermethylation. Curr Top Microbiol Immunol 2006;310:251-74.
30. Esteller M. Relevance of DNA methylation in the management of cancer. Lancet Oncol 2003;4:351-8.
31. Bhalla KN. Epigenetic and chromatin modifiers as targeted therapy of hematologic malignancies. J Clin Oncol 2005;23:3971-93.
32. Das PM, Singal R. DNA methylation and cancer. J Clin Oncol 2004;22:4632-42.
33. Herranz M, Esteller M. DNA methylation and histone modifications in patients with cancer: potential prognostic and therapeutic targets. Methods Mol Biol 2007;361:25-62.
34. Ehrlich M. DNA methylation in cancer: too much, but also too little. Oncogene 2002;21:5400-13.
35. Morey SR, Smiraglia DJ, James SR, Yu J, Moser MT, Foster BA, et al. DNA methylation pathway alterations in an autochthonous murine model of prostate cancer. Cancer Res 2006;66:11659-67.
36. Hoffmann MJ, Schulz WA. Causes and consequences of DNA hypomethylation in human cancer. Biochem Cell Biol 2005;83:296-321.
37. Rauch TA, Zhong X, Wu X, Wang M, Kernstine KH, Wang Z, et al. High-resolution mapping of DNA hypermethylation and hypomethylation in lung cancer. Proc Natl Acad Sci USA 2008;105:252-7.
38. Ehrlich M. DNA hypomethylation in cancer cells. Epigenomics 2009;1:239-59.
39. Gaudet F, Hodgson JG, Eden A, Jackson-Grusby L, Dausman J, Gray JW, et al. Induction of tumors in mice by genomic hypomethylation. Science 2003;300:489-92.
40. Hsiung DT, Marsit CJ, Houseman EA, Eddy K, Furniss CS, McClean MD, et al. Global DNA methylation level in whole blood as a biomarker in head and neck squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev 2007;16:108-14.
41. Moore LE, Pfeiffer RM, Poscablo C, Real FX, Kogevinas M, Silverman D, et al. Genomic DNA hypomethylation as a biomarker for bladder cancer susceptibility in the Spanish Bladder Cancer Study: a case-control study. Lancet Oncol 2008;9:359-66.
42. Wilson AS, Power BE, Molloy PL. DNA hypomethylation and human diseases. Biochim Biophys Acta 2007;1775:138-62.
43. Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, et al. Initial sequencing and analysis of the human genome. Nature 2001;409:860-921.
44. Jordan IK, Rogozin IB, Glazko GV, Koonin EV. Origin of a substantial fraction of human regulatory sequences from transposable elements. Trends Genet 2003;19:68-72.
45. Kochanek S, Renz D, Doerfler W. DNA methylation in the Alu sequences of diploid and haploid primary human cells. EMBO J 1993;12:1141-51.
46. Kaneda A, Tsukamoto T, Takamura-Enya T, Watanabe N, Kaminishi M, Sugimura T, et al. Frequent hypomethylation in multiple promoter CpG islands is associated with global hypomethylation, but not with frequent promoter hypermethylation. Cancer Sci 2004;95:58-64.
47. Ehrlich M, Woods CB, Yu MC, Dubeau L, Yang F, Campan M, et al. Quantitative analysis of associations between DNA hypermethylation, hypomethylation, and DNMT RNA levels in ovarian tumors. Oncogene 2006;25:2636-45.
48. Weisenberger DJ, Campan M, Long TI, Kim M, Woods C, Fiala E, et al. Analysis of repetitive element DNA methylation by MethyLight. Nucleic Acids Res 2005;33:6823-36.
49. Cho NY, Kim BH, Choi M, Yoo EJ, Moon KC, Cho YM, et al. Hypermethylation of CpG island loci and hypomethylation of LINE-1 and Alu repeats in prostate adenocarcinoma and their relationship to clinicopathological features. J Pathol 2007;211:269-77.
50. Estecio MR, Gharibyan V, Shen L, Ibrahim AE, Doshi K, He R, et al. LINE-1 hypomethylation in cancer is highly variable and inversely correlated with microsatellite instability. PLoS One 2007;2:e399.
51. De Smet C, Loriot A. DNA hypomethylation in cancer: epigenetic scars of a neoplastic journey. Epigenetics 2010;5:206-13.
52. Pakneshan P, Tetu B, Rabbani SA. Demethylation of urokinase promoter as a prognostic marker in patients with breast carcinoma. Clin Cancer Res 2004;10:3035-41.
53. Pulukuri SM, Estes N, Patel J, Rao JS. Demethylation-linked activation of urokinase plasminogen activator is involved in progression of prostate cancer. Cancer Res 2007;67:930-9.
54. Kwon MJ, Shin YK. Epigenetic regulation of cancer-associated genes in ovarian cancer. Int J Mol Sci 2011;12:983-1008.
55. Rosty C, Ueki T, Argani P, Jansen M, Yeo CJ, Cameron JL, et al. Overexpression of S100A4 in pancreatic ductal adenocarcinomas is associated with poor differentiation and DNA hypomethylation. Am J Pathol 2002;160:45-50.
56. Feinberg AP, Ohlsson R, Henikoff S. The epigenetic progenitor origin of human cancer. Nat Rev Genet 2006;7:21-33.
57. 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 2002;62:6442-6.
58. Nishiyama R, Qi L, Lacey M, Ehrlich M. Both hypomethylation and hypermethylation in a 0.2-kb region of a DNA repeat in cancer. Mol Cancer Res 2005;3:617-26.
59. Nishiyama R, Qi L, Tsumagari K, Weissbecker K, Dubeau L, Champagne M, et al. A DNA repeat, NBL2, is hypermethylated in some cancers but hypomethylated in others. Cancer Biol Ther 2005;4:440-8.
60. Tsumagari K, Qi L, Jackson K, Shao C, Lacey M, Sowden J, et al. Epigenetics of a tandem DNA repeat: chromatin DNaseI sensitivity and opposite methylation changes in cancers. Nucleic Acids Res 2008;36:2196-207.
61. Kanai Y, Ushijima S, Kondo Y, Nakanishi Y, Hirohashi S. DNA methyltransferase expression and DNA methylation of CPG islands and peri-centromeric satellite regions in human colorectal and stomach cancers. Int J Cancer 2001;91:205-12.
62. Narayan A, Ji W, Zhang XY, Marrogi A, Graff JR, Baylin SB, et al. Hypomethylation of pericentromeric DNA in breast adenocarcinomas. Int J Cancer 1998;77:833-8.
63. De Smet C, Lurquin C, Lethe B, Martelange V, Boon T. DNA methylation is the primary silencing mechanism for a set of germ line-and tumor-specific genes with a CpG-rich promoter. Mol Cell Biol 1999;19:7327-35.
64. Cadieux B, Ching TT, Van den Berg SR, Costello JF. Genomewide hypomethylation in human glioblastomas associated with specific copy number alteration, methylenetetrahydrofolate reductase allele status, and increased proliferation. Cancer Res 2006;66:8469-76.
65. De Smet C, De Backer O, Faraoni I, Lurquin C, Brasseur F, Boon T. The activation of human gene MAGE-1 in tumor cells is correlated with genome-wide demethylation. Proc Natl Acad Sci USA 1996;93:7149-53.
66. Rodriguez-Paredes M, Esteller M. Cancer epigenetics reaches mainstream oncology. Nat Med 2011;17:330-9.
67. Tost J. DNA methylation: an introduction to the biology and the disease-associated changes of a promising biomarker. Mol Biotechnol 2010;44:71-81.
68. Costa FF. Epigenomics in cancer management. Cancer Manag Res 2010;2:255-65.
69. Kuo KC, McCune RA, Gehrke CW, Midgett R, Ehrlich M. Quantitative reversed-phase high performance liquid chromatographic determination of major and modified deoxyribonucleosides in DNA. Nucleic Acids Res 1980;8:4763-76.
70. Annan RS, Kresbach GM, Giese RW, Vouros P. Trace detection of modified DNA bases via moving-belt liquid chromatographymass spectrometry using electrophoric derivatization and negative chemical ionization. J Chromatogr 1989;465:285-96.
71. Fraga MF, Rodriguez R, Canal MJ. Rapid quantification of DNA methylation by high performance capillary electrophoresis. Electrophoresis 2000;21:2990-4.
72. Achwal CW, Chandra HS. A sensitive immunochemical method for detecting 5mC in DNA fragments. FEBS Lett 1982;150:469-72.
73. Braunschweig MH. Quantification of global DNA methylation with infrared fluorescence in liver and muscle tissues of differentially fed boars. Luminescence 2009;24:213-6.
74. Mitchell N, Deangelis JT, Tollefsbol TO. Methylated-CpG Island Recovery Assay. Methods Mol Biol 2011;791:125-33.
75. Balaghi M, Wagner C. DNA methylation in folate deficiency: use of CpG methylase. Biochem Biophys Res Commun 1993;193:1184-90.
76. Harrison J, Stirzaker C, Clark SJ. Cytosines adjacent to methylated CpG sites can be partially resistant to conversion in genomic bisulfite sequencing leading to methylation artifacts. Anal Biochem 1998;264:129-32.
77. Feber A, Wilson GA, Zhang L, Presneau N, Idowu B, Down TA, et al. Comparative methylome analysis of benign and malignant peripheral nerve sheath tumors. Genome Res 2011;21:515-24.
78. Zeimet AG, Fiegl H, Goebel G, Kopp F, Allasia C, Reimer D, et al. DNA ploidy, nuclear size, proliferation index and DNA-hypomethylation in ovarian cancer. Gynecol Oncol 2011;121:24-31.
79. Liao LM, Brennan P, van Bemmel DM, Zaridze D, Matveev V, Janout V, et al. LINE-1 methylation levels in leukocyte DNA and risk of renal cell cancer. PLoS One 2011;6:e27361.
80. Herman JG, Graff JR, Myohanen 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.
81. Eads CA, Danenberg KD, Kawakami K, Saltz LB, Blake C, Shibata D, et al. MethyLight: a high-throughput assay to measure DNA methylation. Nucleic Acids Res 2000;28:E32.
82. Wu HC, John EM, Ferris JS, Keegan TH, Chung WK, Andrulis I, et al. Global DNA methylation levels in girls with and without a family history of breast cancer. Epigenetics 2011;6:29-33.
83. Frommer M, McDonald LE, Millar DS, Collis CM, Watt F, Grigg GW, et al. A genomic sequencing protocol that yields a positive display of 5-methylcytosine residues in individual DNA strands. Proc Natl Acad Sci USA 1992;89:1827-31.
84. Tost J, Dunker J, Gut IG. Analysis and quantification of multiple methylation variable positions in CpG islands by pyrosequencing. Biotechniques 2003;35:152-6.
85. Bourque DK, Peñaherrera, MS, Yuen RK, Van Allen MI, McFadden DE, Robinson WP. The utility of quantitative methylation assays at imprinted genes for the diagnosis of fetal and placental disorders. Clin Genet 2011;79:169-75.
86. Sigalotti L, Fratta E, Bidoli E, Covre A, Parisi G, Colizzi F, et al. Methylation levels of the " long interspersed nucleotide element-1 " repetitive sequences predict survival of melanoma patients. J Transl Med 2011;9:78.
87. Karas M, Hillenkamp F. Laser desorption ionization of proteins with molecular masses exceeding 10, 000 daltons. Anal Chem 1988;60:2299-301.
88. Tanaka K. Protein and polymer analyses up to mlz 100 000 by laser ionization time-of-flight mass spectrometry. Rapid Commun Mass Spectrom 1988;2:151-3.
89. Tost J, Schatz P, Schuster M, Berlin K, Gut IG. Analysis and accurate quantification of CpG methylation by MALDI mass spectrometry. Nucleic Acids Res 2003;31:e50.
90. Sauer S, Lechner D, Berlin K, Lehrach H, Escary JL, Fox N, et al. A novel procedure for efficient genotyping of single nucleotide polymorphisms. Nucleic Acids Res 2000;28:E13.
91. Kanduri M, Cahill N, Goransson H, Enstrom C, Ryan F, Isaksson A, et al. Differential genome-wide array-based methylation profiles in prognostic subsets of chronic lymphocytic leukemia. Blood 2010;115:296-305.
92. Martin-Subero JI, Ammerpohl O, Bibikova M, Wickham-Garcia E, Agirre X, Alvarez S, et al. A comprehensive microarray-based DNA methylation study of 367 hematological neoplasms. PLoS One 2009;4:e6986.
93. Hernandez-Vargas H, Lambert MP, Le Calvez-Kelm F, Gouysse G, McKay-Chopin S, Tavtigian SV, et al. Hepatocellular carcinoma displays distinct DNA methylation signatures with potential as clinical predictors. PLoS One 2010;5:e9749.
94. Martin-Subero JI, Kreuz M, Bibikova M, Bentink S, Ammerpohl O, Wickham-Garcia E, et al. New insights into the biology and origin of mature aggressive B-cell lymphomas by combined epigenomic, genomic, and transcriptional profiling. Blood 2009;113:2488-97.
95. Brock MV, Hooker CM, Ota-Machida E, Han Y, Guo M, Ames S, et al. DNA methylation markers and early recurrence in stage I lung cancer. N Engl J Med 2008;358:1118-28.
96. Lujambio A, Calin GA, Villanueva A, Ropero S, Sanchez-Cespedes M, Blanco D, et al. A microRNA DNA methylation signature for human cancer metastasis. Proc Natl Acad Sci USA 2008;105:13556-61.
97. Fernandez AF, Rosales C, Lopez-Nieva P, Grana O, Ballestar E, Ropero S, et al. The dynamic DNA methylomes of doublestranded DNA viruses associated with human cancer. Genome Res 2009;19:438-51.
98. Toyota M, Ho C, Ahuja N, Jair KW, Li Q, Ohe-Toyota M, et al. Identification of differentially methylated sequences in colorectal cancer by methylated CpG island amplification. Cancer Res 1999;59:2307-12.
99. Huang TH, Perry MR, Laux DE. Methylation profiling of CpG islands in human breast cancer cells. Hum Mol Genet 1999;8:459-70.
100. Rush LJ, Plass C. Restriction landmark genomic scanning for DNA methylation in cancer: past, present, and future applications. Anal Biochem 2002;307:191-201.
101. Frigola J, Ribas M, Risques RA, Peinado MA. Methylome profiling of cancer cells by amplification of inter-methylated sites (AIMS). Nucleic Acids Res 2002;30:e28.
102. Hu M, Yao J, Polyak K. Methylation-specific digital karyotyping. Nat Protoc 2006;1:1621-36.
103. Khulan B, Thompson RF, Ye K, Fazzari MJ, Suzuki M, Stasiek E, et al. Comparative isoschizomer profiling of cytosine methylation: the HELP assay. Genome Res 2006;16:1046-55.
104. Anisowicz A, Huang H, Braunschweiger KI, Liu Z, Giese H, Wang H, et al. A high-throughput and sensitive method to measure global DNA methylation: application in lung cancer. BMC Cancer 2008;8:222.
105. Cross SH, Charlton JA, Nan X, Bird AP. Purification of CpG islands using a methylated DNA binding column. Nat Genet 1994;6:236-44.
106. Shiraishi M, Sekiguchi A, Oates AJ, Terry MJ, Miyamoto Y, Tanaka K, et al. Variable estimation of genomic DNA methylation: a comparison of methyl-CpG binding domain column chromatography and bisulfite genomic sequencing. Anal Biochem 2002;308:182-5.
107. Zou H, Harrington J, Rego RL, Ahlquist DA. A novel method to capture methylated human DNA from stool: implications for colorectal cancer screening. Clin Chem 2007;53:1646-51.
108. Rauch T, Pfeifer GP. Methylated-CpG island recovery assay: a new technique for the rapid detection of methylated-CpG islands in cancer. Lab Invest 2005;85:1172-80.
109. Smith ZD, Gu H, Bock C, Gnirke A, Meissner A. Highthroughput bisulfite sequencing in mammalian genomes. Methods 2009;48:226-32.
110. Harris RA, Wang T, Coarfa C, Nagarajan RP, Hong C, Downey SL, et al. Comparison of sequencing-based methods to profile DNA methylation and identification of monoallelic epigenetic modifications. Nat Biotechnol 2010;28:1097-105.