DNA methylation at enhancer regions: Novel avenues for epigenetic biomarker development

Frontiers in Bioscience - Landmark

Volumn 21, Issue 2, 2016, Pages 430-446

  Clermont, Pier Luc ^a,b   Parolia, Abhijit ^a,c   Liu, Hui Hsuan ^a   Helgason, Cheryl D ^a,b  

^a BRITISH COLUMBIA CANCER RESEARCH CENTRE   (Canada)

^b UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^c UNIVERSITY OF BRITISH COLUMBIA   (Canada)

Author keywords

Biomarker; Cancer; DNA methylation; Enhancer; Epigenetics; Review

Indexed keywords

TUMOR MARKER;

DNA METHYLATION; ENHANCER REGION; GENETIC EPIGENESIS; HUMAN; NEOPLASMS;

BIOMARKERS, TUMOR; DNA METHYLATION; ENHANCER ELEMENTS, GENETIC; EPIGENESIS, GENETIC; HUMANS; NEOPLASMS;

EID: 85016141699     PISSN: 27686701     EISSN: 27686698     Source Type: Journal    
DOI: 10.2741/4399     Document Type: Review

References (132)

1. N. L. Henry and D. F. Hayes: Cancer biomarkers. Mol Oncol, 6(2), 140-6 (2012) DOI: 10.1016/j.molonc.2012.01.010
2. K. Strimbu and J. A. Tavel: What are biomarkers? Curr Opin HIV AIDS, 5(6), 463-6 (2010)
3. A. M. Bailey, Y. Mao, J. Zeng, V. Holla, A. Johnson, L. Brusco, K. Chen, J. Mendelsohn, M. J. Routbort, G. B. Mills and F. Meric-Bernstam: Implementation of biomarkerdriven cancer therapy: existing tools and remaining gaps. Discov Med, 17(92), 101-14 (2014)
4. J. D. Brooks: Translational genomics: the challenge of developing cancer biomarkers. Genome Res, 22(2), 183-7 (2012) DOI: 10.1101/gr.124347.111
5. M. R. Trusheim, E. R. Berndt and F. L. Douglas: Stratified medicine: strategic and economic implications of combining drugs and clinical biomarkers. Nat Rev Drug Discov, 6(4), 287-93 (2007) DOI: 10.1038/nrd2251
6. U. Ladabaum, J. Allen, M. Wandell and S. Ramsey: Colorectal cancer screening with blood-based biomarkers: cost-effectiveness of methylated septin 9 DNA versus current strategies. Cancer Epidemiol Biomarkers Prev, 22(9), 1567-76 (2013) DOI: 10.1158/1055-9965. EPI-13-0204
7. M. E. Hegi, A. C. Diserens, T. Gorlia, M. F. Hamou, N. de Tribolet, M. Weller, J. M. Kros, J. A. Hainfellner, W. Mason, L. Mariani, J. E. Bromberg, P. Hau, R. O. Mirimanoff, J. G. Cairncross, R. C. Janzer and R. Stupp: MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med, 352(10), 997-1003 (2005) DOI: 10.1056/NEJMoa043331
8. K. Woodson, K. J. O'Reilly, J. C. Hanson, D. Nelson, E. L. Walk and J. A. Tangrea: The usefulness of the detection of GSTP1 methylation in urine as a biomarker in the diagnosis of prostate cancer. J Urol, 179(2), 508-11; discussion 511-2 (2008)
9. R. Jaenisch and A. Bird: Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet, 33 Suppl, 245-54 (2003)
10. P. A. Jones and S. B. Baylin: The fundamental role of epigenetic events in cancer. Nat Rev Genet, 3(6), 415-28 (2002)
11. T. A. Chan and S. B. Baylin: Epigenetic biomarkers. Curr Top Microbiol Immunol, 355, 189-216 (2012)
12. M. E. Hegi, L. Liu, J. G. Herman, R. Stupp, W. Wick, M. Weller, M. P. Mehta and M. R. Gilbert: Correlation of O6-methylguanine methyltransferase (MGMT) promoter methylation with clinical outcomes in glioblastoma and clinical strategies to modulate MGMT activity. J Clin Oncol, 26(25), 4189-99 (2008) DOI: 10.1200/JCO.2007.11.5964
13. T. Mikeska and J. M. Craig: DNA methylation biomarkers: cancer and beyond. Genes (Basel), 5(3), 821-64 (2014) DOI: 10.3390/genes5030821
14. R. Holliday and J. E. Pugh: DNA modification mechanisms and gene activity during development. Science, 187(4173), 226-32 (1975) DOI: 10.1126/science.1111098
15. A. D. Riggs: X inactivation, differentiation, and DNA methylation. Cytogenet Cell Genet, 14(1), 9-25 (1975) DOI: 10.1159/000130315
16. P. A. Jones: Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat Rev Genet, 13(7), 484-92 (2012) DOI: 10.1038/nrg3230
17. X. Yang, H. Han, D. D. De Carvalho, F. D. Lay, P. A. Jones and G. Liang: Gene body methylation can alter gene expression and is a therapeutic target in cancer. Cancer Cell, 26(4), 577-90 (2014) DOI: 10.1016/j.ccr.2014.07.028
18. M. T. Bedford and P. D. van Helden: Hypomethylation of DNA in pathological conditions of the human prostate. Cancer Res, 47(20), 5274-6 (1987)
19. A. Portela, J. Liz, V. Nogales, F. Setién, A. Villanueva and M. Esteller: DNA methylation determines nucleosome occupancy in the 5'-CpG islands of tumor suppressor genes. Oncogene, 32(47), 5421-8 (2013) DOI: 10.1038/onc.2013.162
20. D. Aran, S. Sabato and A. Hellman: DNA methylation of distal regulatory sites characterizes dysregulation of cancer genes. Genome Biol, 14(3), R21 (2013)
21. D. Aran and A. Hellman: DNA methylation of transcriptional enhancers and cancer predisposition. Cell, 154(1), 11-3 (2013) DOI: 10.1016/j.cell.2013.06.018
22. M. Petrascheck, D. Escher, T. Mahmoudi, C. P. Verrijzer, W. Schaffner and A. Barberis: DNA looping induced by a transcriptional enhancer in vivo. Nucleic Acids Res, 33(12), 3743-50 (2005) DOI: 10.1093/nar/gki689
23. G. C. Hon, N. Rajagopal, Y. Shen, D. F. McCleary, F. Yue, M. D. Dang and B. Ren: Epigenetic memory at embryonic enhancers identified in DNA methylation maps from adult mouse tissues. Nat Genet, 45(10), 1198-206 (2013) DOI: 10.1038/ng.2746
24. M. S. Kowalczyk, J. R. Hughes, D. Garrick, M. D. Lynch, J. A. Sharpe, J. A. Sloane-Stanley, S. J. McGowan, M. De Gobbi, M. Hosseini, D. Vernimmen, J. M. Brown, N. E. Gray, L. Collavin, R. J. Gibbons, J. Flint, S. Taylor, V. J. Buckle, T. A. Milne, W. G. Wood and D. R. Higgs: Intragenic enhancers act as alternative promoters. Mol Cell, 45(4), 447-58 (2012) DOI: 10.1016/j.molcel.2011.12.021
25. H. P. Saluz, J. Jiricny and J. P. Jost: Genomic sequencing reveals a positive correlation between the kinetics of strand-specific DNA demethylation of the overlapping estradiol/glucocorticoid-receptor binding sites and the rate of avian vitellogenin mRNA synthesis. Proc Natl Acad Sci U S A, 83(19), 7167-71 (1986) DOI: 10.1073/pnas.83.19.7167
26. D. Shlyueva, G. Stampfel and A. Stark: Transcriptional enhancers: from properties to genome-wide predictions. Nat Rev Genet, 15(4), 272-86 (2014) DOI: 10.1038/nrg3682
27. M. Kulis, A. C. Queirós, R. Beekman and J. I. Martín-Subero: Intragenic DNA methylation in transcriptional regulation, normal differentiation and cancer. Biochim Biophys Acta, 1829(11), 1161-74 (2013) DOI: 10.1016/j.bbagrm.2013.08.001
28. A. K. Maunakea, R. P. Nagarajan, M. Bilenky, T. J. Ballinger, C. D'Souza, S. D. Fouse, B. E. Johnson, C. Hong, C. Nielsen, Y. Zhao, G. Turecki, A. Delaney, R. Varhol, N. Thiessen, K. Shchors, V. M. Heine, D. H. Rowitch, X. Xing, C. Fiore, M. Schillebeeckx, S. J. Jones, D. Haussler, M. A. Marra, M. Hirst, T. Wang and J. F. Costello: Conserved role of intragenic DNA methylation in regulating alternative promoters. Nature, 466(7303), 253-7 (2010) DOI: 10.1038/nature09165
29. S. Kangaspeska, B. Stride, R. Métivier, M. Polycarpou-Schwarz, D. Ibberson, R. P. Carmouche, V. Benes, F. Gannon and G. Reid: Transient cyclical methylation of promoter DNA. Nature, 452(7183), 112-5 (2008) DOI: 10.1.038/nature06640
30. M. Wiench, S. John, S. Baek, T. A. Johnson, M. H. Sung, T. Escobar, C. A. Simmons, K. H. Pearce, S. C. Biddie, P. J. Sabo, R. E. Thurman, J. A. Stamatoyannopoulos and G. L. Hager: DNA methylation status predicts cell type-specific enhancer activity. EMBO J, 30(15), 3028-39 (2011) DOI: 10.1.038/emboj.2011.2.10
31. A. Meissner, T. S. Mikkelsen, H. Gu, M. Wernig, J. Hanna, A. Sivachenko, X. Zhang, B. E. Bernstein, C. Nusbaum, D. B. Jaffe, A. Gnirke, R. Jaenisch and E. S. Lander: Genome-scale DNA methylation maps of pluripotent and differentiated cells. Nature, 454(7205), 766-70 (2008) DOI: 10.1.038/nature07107
32. B. Akhtar-Zaidi, R. Cowper-Sal-lari, O. Corradin, A. Saiakhova, C. F. Bartels, D. Balasubramanian, L. Myeroff, J. Lutterbaugh, A. Jarrar, M. F. Kalady, J. Willis, J. H. Moore, P. J. Tesar, T. Laframboise, S. Markowitz, M. Lupien and P. C. Scacheri: Epigenomic enhancer profiling defines a signature of colon cancer. Science, 336(6082), 736-9 (2012) DOI: 10.1.126/science.1217277
33. P. C. Taberlay, A. L. Statham, T. K. Kelly, S. J. Clark and P. A. Jones: Reconfiguration of nucleosome-depleted regions at distal regulatory elements accompanies DNA methylation of enhancers and insulators in cancer. Genome Res, 24(9), 1421-32 (2014) DOI: 10.1.101/gr.163485.1.13
34. G. C. Hon, C. X. Song, T. Du, F. Jin, S. Selvaraj, A. Y. Lee, C. A. Yen, Z. Ye, S. Q. Mao, B. A. Wang, S. Kuan, L. E. Edsall, B. S. Zhao, G. L. Xu, C. He and B. Ren: 5mC Oxidation by Tet2 Modulates Enhancer Activity and Timing of Transcriptome Reprogramming during Differentiation. Mol Cell, 56(2), 286-97 (2014) DOI: 10.1.016/j.molcel.2014.0.8.0.26
35. E. Calo and J. Wysocka: Modification of enhancer chromatin: what, how, and why? Mol Cell, 49(5), 825-37 (2013) DOI: 10.1.016/j.molcel.2013.0.1.0.38
36. J. S. You, T. K. Kelly, D. D. De Carvalho, P. C. Taberlay, G. Liang and P. A. Jones: OCT4 establishes and maintains nucleosomedepleted regions that provide additional layers of epigenetic regulation of its target genes. Proc Natl Acad Sci U S A, 108(35), 14497-502 (2011) DOI: 10.1.073/pnas.1111309108
37. D. Hu, X. Gao, M. A. Morgan, H. M. Herz, E. R. Smith and A. Shilatifard: The MLL3/MLL4 branches of the COMPASS family function as major histone H3K4 monomethylases at enhancers. Mol Cell Biol, 33(23), 4745-54 (2013) DOI: 10.1.128/MCB.01181-13
38. K. J. Ferrari, A. Scelfo, S. Jammula, A. Cuomo, I. Barozzi, A. Stützer, W. Fischle, T. Bonaldi and D. Pasini: Polycomb-dependent H3K27me1 and H3K27me2 regulate active transcription and enhancer fidelity. Mol Cell, 53(1), 49-62 (2014) DOI: 10.1.016/j.molcel.2013.1.0.0.30
39. A. Feldmann, R. Ivanek, R. Murr, D. Gaidatzis, L. Burger and D. Schübeler: Transcription factor occupancy can mediate active turnover of DNA methylation at regulatory regions. PLoS Genet, 9(12), e1003994 (2013) DOI: 10.1.371/journal.pgen. 1003994
40. K. R. Kieffer-Kwon, Z. Tang, E. Mathe, J. Qian, M. H. Sung, G. Li, W. Resch, S. Baek, N. Pruett, L. Grøntved, L. Vian, S. Nelson, H. Zare, O. Hakim, D. Reyon, A. Yamane, H. Nakahashi, A. L. Kovalchuk, J. Zou, J. K. Joung, V. Sartorelli, C. L. Wei, X. Ruan, G. L. Hager, Y. Ruan and R. Casellas: Interactome maps of mouse gene regulatory domains reveal basic principles of transcriptional regulation. Cell, 155(7), 1507-20 (2013) DOI: 10.1.016/j.cell.2013.1.1.0.39
41. F. Schlesinger, A. D. Smith, T. R. Gingeras, G. J. Hannon and E. Hodges: De novo DNA demethylation and noncoding transcription define active intergenic regulatory elements. Genome Res, 23(10), 1601-14 (2013) DOI: 10.1.101/gr.157271.1.13
42. K. Pulakanti, L. Pinello, C. Stelloh, S. Blinka, J. Allred, S. Milanovich, S. Kiblawi, J. Peterson, A. Wang, G. C. Yuan and S. Rao: Enhancer transcribed RNAs arise from hypomethylated, Tet-occupied genomic regions. Epigenetics, 8(12), 1303-20 (2013) DOI: 10.4.161/epi.26597
43. W. Li, D. Notani, Q. Ma, B. Tanasa, E. Nunez, A. Y. Chen, D. Merkurjev, J. Zhang, K. Ohgi, X. Song, S. Oh, H. S. Kim, C. K. Glass and M. G. Rosenfeld: Functional roles of enhancer RNAs for oestrogen-dependent transcriptional activation. Nature, 498(7455), 516-20 (2013) DOI: 10.1.038/nature12210
44. M. T. Lam, W. Li, M. G. Rosenfeld and C. K. Glass: Enhancer RNAs and regulated transcriptional programs. Trends Biochem Sci, 39(4), 170-82 (2014) DOI: 10.1.016/j.tibs.2014.0.2.0.07
45. Y. Kajiyama, J. Tian and J. Locker: Characterization of distant enhancers and promoters in the albumin-alpha-fetoprotein locus during active and silenced expression. J Biol Chem, 281(40), 30122-31 (2006) DOI: 10.1.074/jbc. M603491200
46. S. Mukherjee, H. Erickson and D. Bastia: Enhancer-origin interaction in plasmid R6K involves a DNA loop mediated by initiator protein. Cell, 52(3), 375-83 (1988) DOI: 10.1016/S0092-8674 (88) 80030-8
47. J. Marsman and J. A. Horsfield: Long distance relationships: enhancer-promoter communication and dynamic gene transcription. Biochim Biophys Acta, 1819(11-12), 1217-27 (2012) DOI: 10.1.016/j.bbagrm.2012.1.0.0.08
48. J. Dekker, K. Rippe, M. Dekker and N. Kleckner: Capturing chromosome conformation. Science, 295(5558), 1306-11 (2002) DOI: 10.1.126/science.1067799
49. S. S. Rao, M. H. Huntley, N. C. Durand, E. K. Stamenova, I. D. Bochkov, J. T. Robinson, A. L. Sanborn, I. Machol, A. D. Omer, E. S. Lander and E. L. Aiden: A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping. Cell, 159(7), 1665-80 (2014) DOI: 10.1.016/j.cell.2014.1.1.0.21
50. J. R. Dixon, S. Selvaraj, F. Yue, A. Kim, Y. Li, Y. Shen, M. Hu, J. S. Liu and B. Ren: Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature, 485(7398), 376-80 (2012) DOI: 10.1.038/nature11082
51. A. A. Sérandour, S. Avner, F. Oger, M. Bizot, F. Percevault, C. Lucchetti-Miganeh, G. Palierne, C. Gheeraert, F. Barloy-Hubler, C. L. Péron, T. Madigou, E. Durand, P. Froguel, B. Staels, P. Lefebvre, R. Métivier, J. Eeckhoute and G. Salbert: Dynamic hydroxymethylation of deoxyribonucleic acid marks differentiationassociated enhancers. Nucleic Acids Res, 40(17), 8255-65 (2012) DOI: 10.1.093/nar/gks595
52. A. A. Sérandour, S. Avner, F. Percevault, F. Demay, M. Bizot, C. Lucchetti-Miganeh, F. Barloy-Hubler, M. Brown, M. Lupien, R. Métivier, G. Salbert and J. Eeckhoute: Epigenetic switch involved in activation of pioneer factor FOXA1-dependent enhancers. Genome Res, 21(4), 555-65 (2011) DOI: 10.1.101/gr.111534.1.10
53. A. Kozlenkov, P. Roussos, A. Timashpolsky, M. Barbu, S. Rudchenko, M. Bibikova, B. Klotzle, W. Byne, R. Lyddon, A. F. Di Narzo, Y. L. Hurd, E. V. Koonin and S. Dracheva: Differences in DNA methylation between human neuronal and glial cells are concentrated in enhancers and non-CpG sites. Nucleic Acids Res, 42(1), 109-27 (2014) DOI: 10.1.093/nar/gkt838
54. E. A. Hoivik, T. E. Bjanesoy, O. Mai, S. Okamoto, Y. Minokoshi, Y. Shima, K. Morohashi, U. Boehm and M. Bakke: DNA methylation of intronic enhancers directs tissue-specific expression of steroidogenic factor 1/adrenal 4 binding protein (SF-1/Ad4BP). Endocrinology, 152(5), 2100-12 (2011) DOI: 10.1.210/en. 2010-1305
55. C. Schmidl, M. Klug, T. J. Boeld, R. Andreesen, P. Hoffmann, M. Edinger and M. Rehli: Lineagespecific DNA methylation in T cells correlates with histone methylation and enhancer activity. Genome Res, 19(7), 1165-74 (2009) DOI: 10.1.101/gr.091470.1.09
56. M. Rönnerblad, R. Andersson, T. Olofsson, I. Douagi, M. Karimi, S. Lehmann, I. Hoof, M. de Hoon, M. Itoh, S. Nagao-Sato, H. Kawaji, T. Lassmann, P. Carninci, Y. Hayashizaki, A. R. Forrest, A. Sandelin, K. Ekwall, E. Arner, A. Lennartsson and F. consortium: Analysis of the DNA methylome and transcriptome in granulopoiesis reveals timed changes and dynamic enhancer methylation. Blood, 123(17), e79-89 (2014) DOI: 10.1.182/blood-2013-02-482893
57. J. Nordlund, C. L. Bäcklin, P. Wahlberg, S. Busche, E. C. Berglund, M. L. Eloranta, T. Flaegstad, E. Forestier, B. M. Frost, A. Harila-Saari, M. Heyman, O. G. Jónsson, R. Larsson, J. Palle, L. Rönnblom, K. Schmiegelow, D. Sinnett, S. Söderhäll, T. Pastinen, M. G. Gustafsson, G. Lönnerholm and A. C. Syvänen: Genome-wide signatures of differential DNA methylation in pediatric acute lymphoblastic leukemia. Genome Biol, 14(9), r105 (2013) DOI: 10.1.186/gb-2013-14-9-r105
58. S. Domené, V. F. Bumaschny, F. S. de Souza, L. F. Franchini, S. Nasif, M. J. Low and M. Rubinstein: Enhancer turnover and conserved regulatory function in vertebrate evolution. Philos Trans R Soc Lond B Biol Sci, 368(1632), 20130027 (2013) DOI: 10.1.098/rstb.2013.0.027
59. A. K. Smith, V. Kilaru, M. Kocak, L. M. Almli, K. B. Mercer, K. J. Ressler, F. A. Tylavsky and K. N. Conneely: Methylation quantitative trait loci (meQTLs) are consistently detected across ancestry, developmental stage, and tissue type. BMC Genomics, 15, 145 (2014) DOI: 10.1.186/1471-2164-15-145
60. J. N. Hutchinson, T. Raj, J. Fagerness, E. Stahl, F. T. Viloria, A. Gimelbrant, J. Seddon, M. Daly, A. Chess and R. Plenge: Allelespecific methylation occurs at genetic variants associated with complex disease. PLoS One, 9(6), e98464 (2014) DOI: 10.1.371/journal.pone.0098464
61. H. Heyn, S. Sayols, C. Moutinho, E. Vidal, J. V. Sanchez-Mut, O. A. Stefansson, E. Nadal, S. Moran, J. E. Eyfjord, E. Gonzalez-Suarez, M. A. Pujana and M. Esteller: Linkage of DNA methylation quantitative trait loci to human cancer risk. Cell Rep, 7(2), 331-8 (2014) DOI: 10.1.016/j.celrep. 2014.0.3.0.16
62. O. Ghatnekar, R. Andersson, M. Svensson, U. Persson, U. Ringdahl, P. Zeilon and C. A. Borrebaeck: Modelling the benefits of early diagnosis of pancreatic cancer using a biomarker signature. Int J Cancer, 133(10), 2392-7 (2013) DOI: 10.1.002/ijc.28256
63. N. Vilahur, A. A. Baccarelli, M. Bustamante, S. Agramunt, H. M. Byun, M. F. Fernandez, J. Sunyer and X. Estivill: Storage conditions and stability of global DNA methylation in placental tissue. Epigenomics, 5(3), 341-8 (2013) DOI: 10.2.217/epi.13.2.9
64. A. Dallol, W. Al-Ali, A. Al-Shaibani and F. Al-Mulla: Analysis of DNA methylation in FFPE tissues using the MethyLight technology. Methods Mol Biol, 724, 191-204 (2011) DOI: 10.1.007/978-1-61779-055-3-13
65. A. Widschwendter, H. M. Müller, H. Fiegl, L. Ivarsson, A. Wiedemair, E. Müller-Holzner, G. Goebel, C. Marth and M. Widschwendter: DNA methylation in serum and tumors of cervical cancer patients. Clin Cancer Res, 10(2), 565-71 (2004) DOI: 10.1158/1078-0432. CCR-0825-03
66. J. Yu, T. Zhu, Z. Wang, H. Zhang, Z. Qian, H. Xu, B. Gao, W. Wang, L. Gu, J. Meng, J. Wang, X. Feng, Y. Li, X. Yao and J. Zhu: A novel set of DNA methylation markers in urine sediments for sensitive/specific detection of bladder cancer. Clin Cancer Res, 13(24), 7296-304 (2007) DOI: 10.1.158/1078-0432. CCR-07-0861
67. W. A. Palmisano, K. K. Divine, G. Saccomanno, F. D. Gilliland, S. B. Baylin, J. G. Herman and S. A. Belinsky: Predicting lung cancer by detecting aberrant promoter methylation in sputum. Cancer Res, 60(21), 5954-8 (2000)
68. A. L. Carvalho, R. Henrique, C. Jeronimo, C. S. Nayak, A. N. Reddy, M. O. Hoque, S. Chang, M. Brait, W. W. Jiang, M. M. Kim, Q. Claybourne, D. Goldenberg, Z. Khan, T. Khan, W. H. Westra, D. Sidransky, W. Koch and J. A. Califano: Detection of promoter hypermethylation in salivary rinses as a biomarker for head and neck squamous cell carcinoma surveillance. Clin Cancer Res, 17(14), 4782-9 (2011) DOI: 10.1.158/1078-0432. CCR-11-0324
69. H. Matsubayashi, M. Canto, N. Sato, A. Klein, T. Abe, K. Yamashita, C. J. Yeo, A. Kalloo, R. Hruban and M. Goggins: DNA methylation alterations in the pancreatic juice of patients with suspected pancreatic disease. Cancer Res, 66(2), 1208-17 (2006) DOI: 10.1.158/0008-5472. CAN-05-2664
70. P. W. Laird: Principles and challenges of genomewide DNA methylation analysis. Nat Rev Genet, 11(3), 191-203 (2010) DOI: 10.1.038/nrg2732
71. L. Shen and R. A. Waterland: Methods of DNA methylation analysis. Curr Opin Clin Nutr Metab Care, 10(5), 576-81 (2007) DOI: 10.1.097/MCO.0b013e3282bf6f43
72. L. J. Rush and C. Plass: Restriction landmark genomic scanning for DNA methylation in cancer: past, present, and future applications. Anal Biochem, 307(2), 191-201 (2002) DOI: 10.1016/S0003-2697 (02) 00033-7
73. F. Mohn, M. Weber, D. Schübeler and T. C. Roloff: Methylated DNA immunoprecipitation (MeDIP). Methods Mol Biol, 507, 55-64 (2009) DOI: 10.1.007/978-1-59745-522-0-5
74. F. V. Jacinto, E. Ballestar and M. Esteller: Methyl-DNA immunoprecipitation (MeDIP): hunting down the DNA methylome. Biotechniques, 44(1), 35, 37, 39 passim (2008) DOI: 10.2144/000112708
75. K. L. Thu, E. A. Vucic, J. Y. Kennett, C. Heryet, C. J. Brown, W. L. Lam and I. M. Wilson: Methylated DNA immunoprecipitation. J Vis Exp (23) (2009)
76. N. C. Wong, J. Ng, N. E. Hall, S. Lunke, M. Salmanidis, G. Brumatti, P. G. Ekert, J. M. Craig and R. Saffery: Exploring the utility of human DNA methylation arrays for profiling mouse genomic DNA. Genomics, 102(1), 38-46 (2013) DOI: 10.1.016/j.ygeno. 2013.0.4.0.14
77. K. Patterson, L. Molloy, W. Qu and S. Clark: DNA methylation: bisulphite modification and analysis. J Vis Exp (56) (2011) DOI: 10.3.791/3170
78. M. Frommer, L. E. McDonald, D. S. Millar, C. M. Collis, F. Watt, G. W. Grigg, P. L. Molloy and C. L. Paul: A genomic sequencing protocol that yields a positive display of 5-methylcytosine residues in individual DNA strands. Proc Natl Acad Sci U S A, 89(5), 1827-31 (1992) DOI: 10.1073/pnas.89.5.1827
79. S. J. Docherty, O. S. Davis, C. M. Haworth, R. Plomin and J. Mill: DNA methylation profiling using bisulfite-based epityping of pooled genomic DNA. Methods, 52(3), 255-8 (2010) DOI: 10.1.016/j.ymeth.2010.0.6.0.17
80. B. J. Raney, M. S. Cline, K. R. Rosenbloom, T. R. Dreszer, K. Learned, G. P. Barber, L. R. Meyer, C. A. Sloan, V. S. Malladi, K. M. Roskin, B. B. Suh, A. S. Hinrichs, H. Clawson, A. S. Zweig, V. Kirkup, P. A. Fujita, B. Rhead, K. E. Smith, A. Pohl, R. M. Kuhn, D. Karolchik, D. Haussler and W. J. Kent: ENCODE whole-genome data in the UCSC genome browser (2011 update). Nucleic Acids Res, 39(Database issue), D871-5 (2011) DOI: 10.1.093/nar/gkq1017
81. C. Ladd-Acosta, M. J. Aryee, J. M. Ordway and A. P. Feinberg: Comprehensive highthroughput arrays for relative methylation (CHARM). Curr Protoc Hum Genet, Chapter 20, Unit 20.1.1.-19 (2010) DOI: 10.1.002/0471142905.hg2001s65
82. M. Allinen, R. Beroukhim, L. Cai, C. Brennan, J. Lahti-Domenici, H. Huang, D. Porter, M. Hu, L. Chin, A. Richardson, S. Schnitt, W. R. Sellers and K. Polyak: Molecular characterization of the tumor microenvironment in breast cancer. Cancer Cell, 6(1), 17-32 (2004) DOI: 10.1.016/j.ccr.2004.0.6.0.10
83. M. Hirst: Epigenomics: sequencing the methylome. Methods Mol Biol, 973, 39-54 (2013) DOI: 10.1.007/978-1-62703-281-0-3
84. J. G. Herman, J. R. Graff, S. Myöhänen, B. D. Nelkin and S. B. Baylin: Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci U S A, 93(18), 9821-6 (1996) DOI: 10.1073/pnas.93.18.9821
85. S. Marsh: Pyrosequencing applications. Methods Mol Biol, 373, 15-24 (2007) DOI: 10.1.385/1-59745-377-3:15
86. M. L. Freedman, A. N. Monteiro, S. A. Gayther, G. A. Coetzee, A. Risch, C. Plass, G. Casey, M. De Biasi, C. Carlson, D. Duggan, M. James, P. Liu, J. W. Tichelaar, H. G. Vikis, M. You and I. G. Mills: Principles for the post-GWAS functional characterization of cancer risk loci. Nat Genet, 43(6), 513-8 (2011) DOI: 10.1.038/ng.840
87. R. Andersson, C. Gebhard, I. Miguel-Escalada, I. Hoof, J. Bornholdt, M. Boyd, Y. Chen, X. Zhao, C. Schmidl, T. Suzuki, E. Ntini, E. Arner, E. Valen, K. Li, L. Schwarzfischer, D. Glatz, J. Raithel, B. Lilje, N. Rapin, F. O. Bagger, M. Jørgensen, P. R. Andersen, N. Bertin, O. Rackham, A. M. Burroughs, J. K. Baillie, Y. Ishizu, Y. Shimizu, E. Furuhata, S. Maeda, Y. Negishi, C. J. Mungall, T. F. Meehan, T. Lassmann, M. Itoh, H. Kawaji, N. Kondo, J. Kawai, A. Lennartsson, C. O. Daub, P. Heutink, D. A. Hume, T. H. Jensen, H. Suzuki, Y. Hayashizaki, F. Müller, A. R. Forrest, P. Carninci, M. Rehli, A. Sandelin and F. Consortium: An atlas of active enhancers across human cell types and tissues. Nature, 507(7493), 455-61 (2014) DOI: 10.1.038/nature12787
88. D. Huang and I. Ovcharenko: Identifying causal regulatory SNPs in ChIP-seq enhancers. Nucleic Acids Res, 43(1), 225-36 DOI: 10.1.093/nar/gku1318
89. G. Toperoff, D. Aran, J. D. Kark, M. Rosenberg, T. Dubnikov, B. Nissan, J. Wainstein, Y. Friedlander, E. Levy-Lahad, B. Glaser and A. Hellman: Genome-wide survey reveals predisposing diabetes type 2-related DNA methylation variations in human peripheral blood. Hum Mol Genet, 21(2), 371-83 (2012) DOI: 10.1.093/hmg/ddr472
90. H. Heyn: A symbiotic liaison between the genetic and epigenetic code. Front Genet, 5, 113 (2014) DOI: 10.3.389/fgene.2014.0.0113
91. E. Grundberg, E. Meduri, J. K. Sandling, A. K. Hedman, S. Keildson, A. Buil, S. Busche, W. Yuan, J. Nisbet, M. Sekowska, A. Wilk, A. Barrett, K. S. Small, B. Ge, M. Caron, S. Y. Shin, M. Lathrop, E. T. Dermitzakis, M. I. McCarthy, T. D. Spector, J. T. Bell, P. Deloukas and M. T. H. E. R. Consortium: Global analysis of DNA methylation variation in adipose tissue from twins reveals links to disease-associated variants in distal regulatory elements. Am J Hum Genet, 93(5), 876-90 (2013) DOI: 10.1.016/j.ajhg.2013.1.0.0.04
92. R. A. Smith, D. Manassaram-Baptiste, D. Brooks, V. Cokkinides, M. Doroshenk, D. Saslow, R. C. Wender and O. W. Brawley: Cancer screening in the United States, 2014: a review of current American Cancer Society guidelines and current issues in cancer screening. CA Cancer J Clin, 64(1), 30-51 (2014) DOI: 10.3.322/caac.21212
93. Y. Zhang and A. Jeltsch: The application of next generation sequencing in DNA methylation analysis. Genes (Basel), 1(1), 85-101 (2010) DOI: 10.3.390/genes1010085
94. P. A. Northcott, C. Lee, T. Zichner, A. M. Stütz, S. Erkek, D. Kawauchi, D. J. Shih, V. Hovestadt, M. Zapatka, D. Sturm, D. T. Jones, M. Kool, M. Remke, F. M. Cavalli, S. Zuyderduyn, G. D. Bader, S. VandenBerg, L. A. Esparza, M. Ryzhova, W. Wang, A. Wittmann, S. Stark, L. Sieber, H. Seker-Cin, L. Linke, F. Kratochwil, N. Jäger, I. Buchhalter, C. D. Imbusch, G. Zipprich, B. Raeder, S. Schmidt, N. Diessl, S. Wolf, S. Wiemann, B. Brors, C. Lawerenz, J. Eils, H. J. Warnatz, T. Risch, M. L. Yaspo, U. D. Weber, C. C. Bartholomae, C. von Kalle, E. Turányi, P. Hauser, E. Sanden, A. Darabi, P. Siesjö, J. Sterba, K. Zitterbart, D. Sumerauer, P. van Sluis, R. Versteeg, R. Volckmann, J. Koster, M. U. Schuhmann, M. Ebinger, H. L. Grimes, G. W. Robinson, A. Gajjar, M. Mynarek, K. von Hoff, S. Rutkowski, T. Pietsch, W. Scheurlen, J. Felsberg, G. Reifenberger, A. E. Kulozik, A. von Deimling, O. Witt, R. Eils, R. J. Gilbertson, A. Korshunov, M. D. Taylor, P. Lichter, J. O. Korbel, R. J. Wechsler-Reya and S. M. Pfister: Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma. Nature, 511(7510), 428-34 (2014) DOI: 10.1.038/nature13379
95. D. G. Tenen: Disruption of differentiation in human cancer: AML shows the way. Nat Rev Cancer, 3(2), 89-101 (2003) DOI: 10.1.038/nrc989
96. C. Y. Hu, D. Mohtat, Y. Yu, Y. A. Ko, N. Shenoy, S. Bhattacharya, M. C. Izquierdo, A. S. Park, O. Giricz, N. Vallumsetla, K. Gundabolu, K. Ware, T. D. Bhagat, M. Suzuki, J. Pullman, X. S. Liu, J. M. Greally, K. Susztak and A. Verma: Kidney cancer is characterized by aberrant methylation of tissue-specific enhancers that are prognostic for overall survival. Clin Cancer Res, 20(16), 4349-60 (2014) DOI: 10.1.158/1078-0432. CCR-14-0494
97. T. Klatte, D. B. Seligson, S. B. Riggs, J. T. Leppert, M. K. Berkman, M. D. Kleid, H. Yu, F. F. Kabbinavar, A. J. Pantuck and A. S. Belldegrun: Hypoxia-inducible factor 1 alpha in clear cell renal cell carcinoma. Clin Cancer Res, 13(24), 7388-93 (2007) DOI: 10.1.158/1078-0432. CCR-07-0411
98. G. K. Malhotra, X. Zhao, H. Band and V. Band: Histological, molecular and functional subtypes of breast cancers. Cancer Biol Ther, 10(10), 955-60 (2010) DOI: 10.4161/cbt.10.10.13879
99. J. B. Andersen, V. M. Factor, J. U. Marquardt, C. Raggi, Y. H. Lee, D. Seo, E. A. Conner and S. S. Thorgeirsson: An integrated genomic and epigenomic approach predicts therapeutic response to zebularine in human liver cancer. Sci Transl Med, 2(54), 54ra77 (2010) DOI: 10.1.126/scitranslmed.3001338
100. V. Bonadona, P. Saltel, F. Desseigne, H. Mignotte, J. C. Saurin, Q. Wang, O. Sinilnikova, S. Giraud, G. Freyer, H. Plauchu, A. Puisieux and C. Lasset: Cancer patients who experienced diagnostic genetic testing for cancer susceptibility: reactions and behavior after the disclosure of a positive test result. Cancer Epidemiol Biomarkers Prev, 11(1), 97-104 (2002)
101. N. Pavlidis and G. Pentheroudakis: Cancer of unknown primary site: 20 questions to be answered. Ann Oncol, 21 Suppl 7, vii303-7 (2010) DOI: 10.1.093/annonc/mdq278
102. S. Hoelder, P. A. Clarke and P. Workman: Discovery of small molecule cancer drugs: successes, challenges and opportunities. Mol Oncol, 6(2), 155-76 (2012) DOI: 10.1.016/j.molonc.2012.0.2.0.04
103. E. Drucker and K. Krapfenbauer: Pitfalls and limitations in translation from biomarker discovery to clinical utility in predictive and personalised medicine. EPMA J, 4(1), 7 (2013) DOI: 10.1.186/1878-5085-4-7
104. C. Sessa, A. Guibal, G. Del Conte and C. Rüegg: Biomarkers of angiogenesis for the development of antiangiogenic therapies in oncology: tools or decorations? Nat Clin Pract Oncol, 5(7), 378-91 (2008) DOI: 10.1.038/ncponc1150
105. H. Yan, Q. L. Wu, C. Y. Sun, L. S. Ai, J. Deng, L. Zhang, L. Chen, Z. B. Chu, B. Tang, K. Wang, X. F. Wu, J. Xu and Y. Hu: piRNA-823 contributes to tumorigenesis by regulating de novo DNA methylation and angiogenesis in multiple myeloma. Leukemia, 29(1), 196-206 (2015) DOI: 10.1.038/leu.2014.1.35
106. H. Quentmeier, S. Eberth, J. Romani, H. A. Weich, M. Zaborski and H. G. Drexler: DNA methylation regulates expression of VEGF-R2 (KDR) and VEGF-R3 (FLT4). BMC Cancer, 12, 19 (2012) DOI: 10.1.186/1471-2407-12-19
107. M. P. Cooper and J. F. Keaney: Epigenetic control of angiogenesis via DNA methylation. Circulation, 123(25), 2916-8 (2011) DOI: 10.1.161/CIRCULATIONAHA.111.0.33092
108. T. N. Schumacher, C. Kesmir and M. M. van Buuren: Biomarkers in cancer immunotherapy. Cancer Cell, 27(1), 12-4 (2015) DOI: 10.1.016/j.ccell.2014.1.2.0.04
109. C. Abi Khalil: The emerging role of epigenetics in cardiovascular disease. Ther Adv Chronic Dis, 5(4), 178-87 (2014) DOI: 10.1.177/2040622314529325
110. C. Ling and L. Groop: Epigenetics: a molecular link between environmental factors and type 2 diabetes. Diabetes, 58(12), 2718-25 (2009) DOI: 10.2.337/db09-1003
111. J. S. You and P. A. Jones: Cancer genetics and epigenetics: two sides of the same coin? Cancer Cell, 22(1), 9-20 (2012) DOI: 10.1.016/j.ccr.2012.0.6.0.08
112. M. A. Dawson and T. Kouzarides: Cancer epigenetics: from mechanism to therapy. Cell, 150(1), 12-27 (2012) DOI: 10.1.016/j.cell.2012.0.6.0.13
113. C. H. Arrowsmith, C. Bountra, P. V. Fish, K. Lee and M. Schapira: Epigenetic protein families: a new frontier for drug discovery. Nat Rev Drug Discov, 11(5), 384-400 (2012) DOI: 10.1.038/nrd3674
114. P. Fenaux, G. J. Mufti, E. Hellstrom-Lindberg, V. Santini, C. Finelli, A. Giagounidis, R. Schoch, N. Gattermann, G. Sanz, A. List, S. D. Gore, J. F. Seymour, J. M. Bennett, J. Byrd, J. Backstrom, L. Zimmerman, D. McKenzie, C. Beach, L. R. Silverman and I. V. H.-R. M. S. S. Group: Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol, 10(3), 223-32 (2009) DOI: 10.1.016/S1470-2045 (09) 70003-8
115. H. Kantarjian, J. P. Issa, C. S. Rosenfeld, J. M. Bennett, M. Albitar, J. DiPersio, V. Klimek, J. Slack, C. de Castro, F. Ravandi, R. Helmer, L. Shen, S. D. Nimer, R. Leavitt, A. Raza and H. Saba: Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study. Cancer, 106(8), 1794-803 (2006) DOI: 10.1.002/cncr.21792
116. U. Platzbecker, M. Wermke, J. Radke, U. Oelschlaegel, F. Seltmann, A. Kiani, I. M. Klut, H. Knoth, C. Röllig, J. Schetelig, B. Mohr, X. Graehlert, G. Ehninger, M. Bornhäuser and C. Thiede: Azacitidine for treatment of imminent relapse in MDS or AML patients after allogeneic HSCT: results of the RELAZA trial. Leukemia, 26(3), 381-9 (2012) DOI: 10.1.038/leu.2011.2.34
117. H. M. Herz, D. Hu and A. Shilatifard: Enhancer malfunction in cancer. Mol Cell, 53(6), 859-66 (2014) DOI: 10.1.016/j.molcel.2014.0.2.0.33
118. Y. G. Lee, I. Kim, S. S. Yoon, S. Park, J. W. Cheong, Y. H. Min, J. O. Lee, S. M. Bang, H. G. Yi, C. S. Kim, Y. Park, B. S. Kim, Y. C. Mun, C. M. Seong, J. Park, J. H. Lee, S. Y. Kim, H. G. Lee, Y. K. Kim, H. J. Kim and K. S. o. H. A. M. w. party: Comparative analysis between azacitidine and decitabine for the treatment of myelodysplastic syndromes. Br J Haematol, 161(3), 339-47 (2013) DOI: 10.1.111/bjh.12256
119. W. Zhang, Y. E. Wang, Y. Zhang, X. Leleu, M. Reagan, Y. Mishima, S. Glavey, S. Manier, A. Sacco, B. Jiang, A. M. Roccaro and I. M. Ghobrial: Global epigenetic regulation of microRNAs in multiple myeloma. PLoS One, 9(10), e110973 (2014) DOI: 10.1.371/journal.pone.0110973
120. J. Datta, H. Kutay, M. W. Nasser, G. J. Nuovo, B. Wang, S. Majumder, C. G. Liu, S. Volinia, C. M. Croce, T. D. Schmittgen, K. Ghoshal and S. T. Jacob: Methylation mediated silencing of MicroRNA-1 gene and its role in hepatocellular carcinogenesis. Cancer Res, 68(13), 5049-58 (2008) DOI: 10.1.158/0008-5472. CAN-07-6655
121. R. L. Yim, K. Y. Wong, Y. L. Kwong, F. Loong, C. Y. Leung, R. Chu, W. W. Lam, P. K. Hui, R. Lai and C. S. Chim: Methylation of miR-155-3p in mantle cell lymphoma and other non-Hodgkin's lymphomas. Oncotarget, 5(20), 9770-82 (2014)
122. U. A. Ørom, T. Derrien, M. Beringer, K. Gumireddy, A. Gardini, G. Bussotti, F. Lai, M. Zytnicki, C. Notredame, Q. Huang, R. Guigo and R. Shiekhattar: Long noncoding RNAs with enhancer-like function in human cells. Cell, 143(1), 46-58 (2010) DOI: 10.1.016/j.cell.2010.0.9.0.01
123. F. Lai, U. A. Orom, M. Cesaroni, M. Beringer, D. J. Taatjes, G. A. Blobel and R. Shiekhattar: Activating RNAs associate with Mediator to enhance chromatin architecture and transcription. Nature, 494(7438), 497-501 (2013) DOI: 10.1.038/nature11884
124. T. K. Kim, M. Hemberg, J. M. Gray, A. M. Costa, D. M. Bear, J. Wu, D. A. Harmin, M. Laptewicz, K. Barbara-Haley, S. Kuersten, E. Markenscoff-Papadimitriou, D. Kuhl, H. Bito, P. F. Worley, G. Kreiman and M. E. Greenberg: Widespread transcription at neuronal activity-regulated enhancers. Nature, 465(7295), 182-7 (2010) DOI: 10.1.038/nature09033
125. D. Wang, I. Garcia-Bassets, C. Benner, W. Li, X. Su, Y. Zhou, J. Qiu, W. Liu, M. U. Kaikkonen, K. A. Ohgi, C. K. Glass, M. G. Rosenfeld and X. D. Fu: Reprogramming transcription by distinct classes of enhancers functionally defined by eRNA. Nature, 474(7351), 390-4 (2011) DOI: 10.1.038/nature10006
126. N. Hah, C. G. Danko, L. Core, J. J. Waterfall, A. Siepel, J. T. Lis and W. L. Kraus: A rapid, extensive, and transient transcriptional response to estrogen signaling in breast cancer cells. Cell, 145(4), 622-34 (2011) DOI: 10.1.016/j.cell.2011.0.3.0.42
127. C. A. Melo, J. Drost, P. J. Wijchers, H. van de Werken, E. de Wit, J. A. Oude Vrielink, R. Elkon, S. A. Melo, N. Léveillé, R. Kalluri, W. de Laat and R. Agami: eRNAs are required for p53-dependent enhancer activity and gene transcription. Mol Cell, 49(3), 524-35 (2013) DOI: 10.1.016/j.molcel.2012.1.1.0.21
128. A. R. MacLeod and M. Szyf: Expression of antisense to DNA methyltransferase mRNA induces DNA demethylation and inhibits tumorigenesis. J Biol Chem, 270(14), 8037-43 (1995) DOI: 10.1074/jbc.270.14.8037
129. M. T. Lam, H. Cho, H. P. Lesch, D. Gosselin, S. Heinz, Y. Tanaka-Oishi, C. Benner, M. U. Kaikkonen, A. S. Kim, M. Kosaka, C. Y. Lee, A. Watt, T. R. Grossman, M. G. Rosenfeld, R. M. Evans and C. K. Glass: Rev-Erbs repress macrophage gene expression by inhibiting enhancer-directed transcription. Nature, 498(7455), 511-5 (2013) DOI: 10.1.038/nature12209
130. L. Lambertini: Genomic imprinting: sensing the environment and driving the fetal growth. Curr Opin Pediatr, 26(2), 237-42 (2014) DOI: 10.1.097/MOP.0000000000000072
131. C. Lu and C. B. Thompson: Metabolic regulation of epigenetics. Cell Metab, 16(1), 9-17 (2012) DOI: 10.1.016/j.cmet.2012.0.6.0.01
132. E. Chipumuro, E. Marco, C. L. Christensen, N. Kwiatkowski, T. Zhang, C. M. Hatheway, B. J. Abraham, B. Sharma, C. Yeung, A. Altabef, A. Perez-Atayde, K. K. Wong, G. C. Yuan, N. S. Gray, R. A. Young and R. E. George: CDK7 Inhibition Suppresses Super-Enhancer-Linked Oncogenic Transcription in MYCNDriven Cancer. Cell, 159(5), 1126-39 (2014) DOI: 10.1.016/j.cell.2014.1.0.0.24