DNA methylation signatures for breast cancer classification and prognosis

Genome Medicine

Volumn 4, Issue 3, 2012, Pages

  Szyf, Moshe ^a  

^a MCGILL UNIVERSITY   (Canada)

Author keywords

Breast cancer metastasis; Breast cancer stages; DNA methylation; Epigenetics; Hypermethylation; Hypomethylation; Whole genome methods

Indexed keywords

BIOLOGICAL MARKER; DNA METHYLTRANSFERASE; EPIDERMAL GROWTH FACTOR RECEPTOR 2; ESTROGEN RECEPTOR; INTERLEUKIN 4; INTERLEUKIN 6; METALLOPROTEINASE;

BECKWITH WIEDEMANN SYNDROME; BLOOD ANALYSIS; BREAST CANCER; CANCER CELL CULTURE; CANCER CLASSIFICATION; CANCER DIAGNOSIS; CANCER PATIENT; CANCER PROGNOSIS; CANCER STAGING; CARDIOVASCULAR DISEASE; CHROMATIN STRUCTURE; DIABETIC PATIENT; DNA BINDING; DNA METHYLATION; DNA REPLICATION; ENZYME ACTIVITY; GENE CONTROL; GENE EXPRESSION; GENE MAPPING; GENETIC ANALYSIS; GENETIC ASSOCIATION; GENETIC PROCEDURES; GENOME IMPRINTING; HAPPY PUPPET SYNDROME; HUMAN; HUMAN GENOME; IMMUNOHISTOCHEMISTRY; IMMUNOPRECIPITATION; LIVER CANCER; LIVER CELL CARCINOMA; LUPUS VULGARIS; METASTASIS; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; PROMOTER REGION; REVIEW; SCHIZOPHRENIA; SIGNAL TRANSDUCTION; T LYMPHOCYTE; TUMOR BIOPSY;

EID: 84858983373     PISSN: None     EISSN: 1756994X     Source Type: Journal    
DOI: 10.1186/gm325     Document Type: Review

References (109)

1. Perou CM, Børresen-Dale AL. Systems biology and genomics of breast cancer. Cold Spring Harb Perspect Biol 2011, 3:a003293. 10.1101/cshperspect.a003293, 21047916.
2. Costanzo M, Baryshnikova A, Myers CL, Andrews B, Boone C. Charting the genetic interaction map of a cell. Curr Opin Biotechnol 2011, 22:66-74. 10.1016/j.copbio.2010.11.001, 21111604.
3. Flanagan JM, Cocciardi S, Waddell N, Johnstone CN, Marsh A, Henderson S, Simpson P, da Silva L, Khanna K, Lakhani S, Boshoff C, Chenevix-Trench G. DNA methylome of familial breast cancer identifies distinct profiles defined by mutation status. Am J Hum Genet 2010, 86:420-433. 10.1016/j.ajhg.2010.02.008, 2833389, 20206335.
4. Kristensen VN, Vaske CJ, Ursini-Siegel J, Van Loo P, Nordgard SH, Sachidanandam R, Sørlie T, Wärnberg F, Haakensen VD, Helland A, Naume B, Perou CM, Haussler D, Troyanskaya OG, Børresen-Dale AL. Integrated molecular profiles of invasive breast tumors and ductal carcinoma in situ (DCIS) reveal differential vascular and interleukin signaling. Proc Natl Acad Sci USA 2012, 109:2802-2807. 10.1073/pnas.1108781108, 21908711.
5. Dedeurwaerder S, Desmedt C, Calonne E. Largest ever DNA methylation dataset for breast cancer completed. Expert Rev Mol Diagn 2011, 11:470.
6. Razin A, Riggs AD. DNA methylation and gene function. Science 1980, 210:604-610. 10.1126/science.6254144, 6254144.
7. Razin A, Szyf M. DNA methylation patterns. Formation and function. Biochim Biophys Acta 1984, 782:331-342.
8. Lister R, Pelizzola M, Dowen RH, Hawkins RD, Hon G, Tonti-Filippini J, Nery JR, Lee L, Ye Z, Ngo QM, Edsall L, Antosiewicz-Bourget J, Stewart R, Ruotti V, Millar AH, Thomson JA, Ren B, Ecker JR. Human DNA methylomes at base resolution show widespread epigenomic differences. Nature 2009, 462:315-322. 10.1038/nature08514, 2857523, 19829295.
9. Adams R, Turnbull J, Smillie E, Burdon R. DNA methylation in nuclei and studies using a purified DNA methylase from ascites cells. Post-synthetic Modification of Macromolecules 1975, 39-48. Amsterdam: North-Holland, Antoni F, Farago A.
10. Jeltsch A. Molecular enzymology of mammalian DNA methyltransferases. Curr Top Microbiol Immunol 2006, 301:203-225. 10.1007/3-540-31390-7_7, 16570849.
11. Gruenbaum Y, Cedar H, Razin A. Substrate and sequence specificity of a eukaryotic DNA methylase. Nature 1982, 295:620-622. 10.1038/295620a0, 7057921.
12. Stein R, Gruenbaum Y, Pollack Y, Razin A, Cedar H. Clonal inheritance of the pattern of DNA methylation in mouse cells. Proc Natl Acad Sci USA 1982, 79:61-65. 10.1073/pnas.79.1.61, 345661, 6459581.
13. Okano M, Xie S, Li E. Cloning and characterization of a family of novel mammalian DNA (cytosine-5) methyltransferases. Nat Genet 1998, 19:219-220. 10.1038/890, 9662389.
14. Fuks F, Burgers WA, Brehm A, Hughes-Davies L, Kouzarides T. DNA methyltransferase Dnmt1 associates with histone deacetylase activity. Nat Genet 2000, 24:88-91. 10.1038/71750, 10615135.
15. Rountree MR, Bachman KE, Baylin SB. DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at replication foci. Nat Genet 2000, 25:269-277. 10.1038/77023, 10888872.
16. Fuks F, Hurd PJ, Wolf D, Nan X, Bird AP, Kouzarides T. The methyl-CpG-binding protein MeCP2 links DNA methylation to histone methylation. J Biol Chem 2003, 278:4035-4040. 10.1074/jbc.M210256200, 12427740.
17. Viré E, Brenner C, Deplus R, Blanchon L, Fraga M, Didelot C, Morey L, Van Eynde A, Bernard D, Vanderwinden JM, Bollen M, Esteller M, Di Croce L, de Launoit Y, Fuks F. The Polycomb group protein EZH2 directly controls DNA methylation. Nature 2006, 439:871-874. 10.1038/nature04431, 16357870.
18. Bostick M, Kim JK, Estève PO, Clark A, Pradhan S, Jacobsen SE. UHRF1 plays a role in maintaining DNA methylation in mammalian cells. Science 2007, 317:1760-1764. 10.1126/science.1147939, 17673620.
19. Sharif J, Muto M, Takebayashi S, Suetake I, Iwamatsu A, Endo TA, Shinga J, Mizutani-Koseki Y, Toyoda T, Okamura K, Tajima S, Mitsuya K, Okano M, Koseki H. The SRA protein Np95 mediates epigenetic inheritance by recruiting Dnmt1 to methylated DNA. Nature 2007, 450:908-912. 10.1038/nature06397, 17994007.
20. Szyf M, Tanigawa G, McCarthy PL. A DNA signal from the Thy-1 gene defines de novo methylation patterns in embryonic stem cells. Mol Cell Biol 1990, 10:4396-4400. 360998, 1973527.
21. Brandeis M, Frank D, Keshet I, Siegfried Z, Mendelsohn M, Nemes A, Temper V, Razin A, Cedar H. Sp1 elements protect a CpG island from de novo methylation. Nature 1994, 371:435-438. 10.1038/371435a0, 8090226.
22. Stadler MB, Murr R, Burger L, Ivanek R, Lienert F, Schöler A, Wirbelauer C, Oakeley EJ, Gaidatzis D, Tiwari VK, Schübeler D. DNA-binding factors shape the mouse methylome at distal regulatory regions. Nature 2011, 480:490-495.
23. Razin A, Cedar H. Distribution of 5-methylcytosine in chromatin. Proc Natl Acad Sci USA 1977, 74:2725-2728. 10.1073/pnas.74.7.2725, 431263, 268622.
24. Rauch TA, Wu X, Zhong X, Riggs AD, Pfeifer GP. A human B cell methylome at 100-base pair resolution. Proc Natl Acad Sci USA 2009, 106:671-678. 10.1073/pnas.0812399106, 2621253, 19139413.
25. Comb M, Goodman HM. CpG methylation inhibits proenkephalin gene expression and binding of the transcription factor AP-2. Nucleic Acids Res 1990, 18:3975-3982. 10.1093/nar/18.13.3975, 331101, 1695733.
26. Inamdar NM, Ehrlich KC, Ehrlich M. CpG methylation inhibits binding of several sequence-specific DNA-binding proteins from pea, wheat, soybean and cauliflower. Plant Mol Biol 1991, 17:111-123. 10.1007/BF00036811, 1831056.
27. Nan X, Campoy FJ, Bird A. MeCP2 is a transcriptional repressor with abundant binding sites in genomic chromatin. Cell 1997, 88:471-481. 10.1016/S0092-8674(00)81887-5, 9038338.
28. Zhang Y, Ng HH, Erdjument-Bromage H, Tempst P, Bird A, Reinberg D. Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation. Genes Dev 1999, 13:1924-1935. 10.1101/gad.13.15.1924, 316920, 10444591.
29. Hellman A, Chess A. Gene body-specific methylation on the active X chromosome. Science 2007, 315:1141-1143. 10.1126/science.1136352, 17322062.
30. Suzuki M, Oda M, Ramos MP, Pascual M, Lau K, Stasiek E, Agyiri F, Thompson RF, Glass JL, Jing Q, Sandstrom R, Fazzari MJ, Hansen RS, Stamatoyannopoulos JA, McLellan AS, Greally JM. Late-replicating heterochromatin is characterized by decreased cytosine methylation in the human genome. Genome Res 2011, 21:1833-1840. 10.1101/gr.116509.110, 21957152.
31. Siegal ML, Promislow DE, Bergman A. Functional and evolutionary inference in gene networks: does topology matter?. Genetica 2007, 129:83-103.
32. Grayson DR, Jia X, Chen Y, Sharma RP, Mitchell CP, Guidotti A, Costa E. Reelin promoter hypermethylation in schizophrenia. Proc Natl Acad Sci USA 2005, 102:9341-9346. 10.1073/pnas.0503736102, 1166626, 15961543.
33. Petronis A, Gottesman II, Kan P, Kennedy JL, Basile VS, Paterson AD, Popendikyte V. Monozygotic twins exhibit numerous epigenetic differences: clues to twin discordance?. Schizophr Bull 2003, 29:169-178. 10.1093/oxfordjournals.schbul.a006988, 12908672.
34. Veldic M, Guidotti A, Maloku E, Davis JM, Costa E. In psychosis, cortical interneurons overexpress DNA-methyltransferase 1. Proc Natl Acad Sci USA 2005, 102:2152-2157. 10.1073/pnas.0409665102, 548582, 15684088.
35. Balada E, Ordi-Ros J, Serrano-Acedo S, Martinez-Lostao L, Rosa-Leyva M, Vilardell-Tarrés M. Transcript levels of DNA methyltransferases DNMT1, DNMT3A and DNMT3B in CD4+ T cells from patients with systemic lupus erythematosus. Immunology 2008, 124:339-347. 10.1111/j.1365-2567.2007.02771.x, 2440828, 18194272.
36. Balada E, Ordi-Ros J, Vilardell-Tarrés M. DNA methylation and systemic lupus erythematosus. Ann N Y Acad Sci 2007, 1108:127-136. 10.1196/annals.1422.015, 17893979.
37. Yung RL, Richardson BC. Role of T cell DNA methylation in lupus syndromes. Lupus 1994, 3:487-491. 10.1177/096120339400300611, 7535621.
38. Gluckman PD, Hanson MA, Bateson P, Beedle AS, Law CM, Bhutta ZA, Anokhin KV, Bougnères P, Chandak GR, Dasgupta P, Smith GD, Ellison PT, Forrester TE, Gilbert SF, Jablonka E, Kaplan H, Prentice AM, Simpson SJ, Uauy R, West-Eberhard MJ. Towards a new developmental synthesis: adaptive developmental plasticity and human disease. Lancet 2009, 373:1654-1657. 10.1016/S0140-6736(09)60234-8, 19427960.
39. Stenvinkel P, Karimi M, Johansson S, Axelsson J, Suliman M, Lindholm B, Heimbürger O, Barany P, Alvestrand A, Nordfors L, Qureshi AR, Ekström TJ, Schalling M. Impact of inflammation on epigenetic DNA methylation - a novel risk factor for cardiovascular disease?. J Intern Med 2007, 261:488-499. 10.1111/j.1365-2796.2007.01777.x, 17444888.
40. Ling C, Del Guerra S, Lupi R, Rönn T, Granhall C, Luthman H, Masiello P, Marchetti P, Groop L, Del Prato S. Epigenetic regulation of PPARGC1A in human type 2 diabetic islets and effect on insulin secretion. Diabetologia 2008, 51:615-622. 10.1007/s00125-007-0916-5, 2270364, 18270681.
41. Maier S, Olek A. Diabetes: a candidate disease for efficient DNA methylation profiling. J Nutr 2002, 132:2440S-2443S.
42. Volkmar M, Dedeurwaerder S, Cunha DA, Ndlovu MN, Defrance M, Deplus R, Calonne E, Volkmar U, Igoillo-Esteve M, Naamane N, Del Guerra S, Masini M, Bugliani M, Marchetti P, Cnop M, Eizirik DL, Fuks F. DNA methylation profiling identifies epigenetic dysregulation in pancreatic islets from type 2 diabetic patients. EMBO J 2012, 31:1405-1426. 10.1038/emboj.2011.503, 22293752.
43. Corwin EJ. The concept of epigenetics and its role in the development of cardiovascular disease: commentary on "new and emerging theories of cardiovascular disease". Biol Res Nurs 2004, 6:11-6. discussion 21-3, 10.1177/1099800404264779, 15186703.
44. Hanson MA, Gluckman PD. Developmental origins of health and disease: new insights. Basic Clin Pharmacol Toxicol 2008, 102:90-93. 10.1111/j.1742-7843.2007.00186.x, 18226060.
45. Cornacchia E, Golbus J, Maybaum J, Strahler J, Hanash S, Richardson B. Hydralazine and procainamide inhibit T cell DNA methylation and induce autoreactivity. J Immunol 1988, 140:2197-2200.
46. Mi XB, Zeng FQ. Hypomethylation of interleukin-4 and -6 promoters in T cells from systemic lupus erythematosus patients. Acta Pharmacol Sin 2008, 29:105-112. 10.1111/j.1745-7254.2008.00739.x, 18158872.
47. Sapienza C. Parental imprinting of genes. Sci Am 1990, 263:52-60. 10.1038/scientificamerican1090-52, 2146740.
48. Polychronakos C. Parental imprinting of the genes for IGF-II and its receptor. Adv Exp Med Biol 1993, 343:189-203. 10.1007/978-1-4615-2988-0_19, 8184739.
49. Tilghman SM, Bartolomei MS, Webber AL, Brunkow ME, Saam J, Leighton PA, Pfeifer K, Zemel S. Parental imprinting of the H19 and Igf2 genes in the mouse. Cold Spring Harb Symp Quant Biol 1993, 58:287-295. 10.1101/SQB.1993.058.01.034, 7956041.
50. Mannens M, Hoovers JM, Redeker E, Verjaal M, Feinberg AP, Little P, Boavida M, Coad N, Steenman M, Bliek J. Parental imprinting of human chromosome region 11p15.3-pter involved in the Beckwith-Wiedemann syndrome and various human neoplasia. Eur J Hum Genet 1994, 2:3-23.
51. Lalande M. Parental imprinting and human disease. Annu Rev Genet 1996, 30:173-195. 10.1146/annurev.genet.30.1.173, 8982453.
52. Kondo M, Suzuki H, Ueda R, Osada H, Takagi K, Takahashi T, Takahashi T. Frequent loss of imprinting of the H19 gene is often associated with its overexpression in human lung cancers. Oncogene 1995, 10:1193-1198.
53. Fukuzawa R, Umezawa A, Ochi K, Urano F, Ikeda H, Hata J. High frequency of inactivation of the imprinted H19 gene in "sporadic" hepatoblastoma. Int J Cancer 1999, 82:490-497. 10.1002/(SICI)1097-0215(19990812)82:4<490::AID-IJC4>3.0.CO;2-I, 10404060.
54. Douc-Rasy S, Barrois M, Fogel S, Ahomadegbe JC, Stéhelin D, Coll J, Riou G. High incidence of loss of heterozygosity and abnormal imprinting of H19 and IGF2 genes in invasive cervical carcinomas. Uncoupling of H19 and IGF2 expression and biallelic hypomethylation of H19. Oncogene 1996, 12:423-430.
55. Szyf M. DNA methylation properties: consequences for pharmacology. Trends Pharmacol Sci 1994, 15:233-238. 10.1016/0165-6147(94)90317-4, 7940985.
56. Baylin SB, Esteller M, Rountree MR, Bachman KE, Schuebel K, Herman JG. Aberrant patterns of DNA methylation, chromatin formation and gene expression in cancer. Hum Mol Genet 2001, 10:687-692. 10.1093/hmg/10.7.687, 11257100.
57. Issa JP, Vertino PM, Wu J, Sazawal S, Celano P, Nelkin BD, Hamilton SR, Baylin SB. Increased cytosine DNA-methyltransferase activity during colon cancer progression. J Natl Cancer Inst 1993, 85:1235-1240. 10.1093/jnci/85.15.1235, 8331684.
58. Ehrlich M. DNA methylation in cancer: too much, but also too little. Oncogene 2002, 21:5400-5413. 10.1038/sj.onc.1205651, 12154403.
59. Hansen KD, Timp W, Bravo HC, Sabunciyan S, Langmead B, McDonald OG, Wen B, Wu H, Liu Y, Diep D, Briem E, Zhang K, Irizarry RA, Feinberg AP. Increased methylation variation in epigenetic domains across cancer types. Nat Genet 2011, 43:768-775. 10.1038/ng.865, 3145050, 21706001.
60. Shteper PJ, Zcharia E, Ashhab Y, Peretz T, Vlodavsky I, Ben-Yehuda D. Role of promoter methylation in regulation of the mammalian heparanase gene. Oncogene 2003, 22:7737-7749. 10.1038/sj.onc.1207056, 14586400.
61. Shukeir N, Pakneshan P, Chen G, Szyf M, Rabbani SA. Alteration of the methylation status of tumor-promoting genes decreases prostate cancer cell invasiveness and tumorigenesis in vitro and in vivo. Cancer Res 2006, 66:9202-9210. 10.1158/0008-5472.CAN-06-1954, 16982764.
62. Pakneshan P, Szyf M, Farias-Eisner R, Rabbani SA. Reversal of the hypomethylation status of urokinase (uPA) promoter blocks breast cancer growth and metastasis. J Biol Chem 2004, 279:31735-31744. 10.1074/jbc.M401669200, 15150277.
63. Stefanska B, Huang J, Bhattacharyya B, Suderman M, Hallett M, Han ZG, Szyf M. Definition of the landscape of promoter DNA hypomethylation in liver cancer. Cancer Res 2011, 71:5891-5903. 10.1158/0008-5472.CAN-10-3823, 21747116.
64. Ateeq B, Unterberger A, Szyf M, Rabbani SA. Pharmacological inhibition of DNA methylation induces proinvasive and prometastatic genes in vitro and in vivo. Neoplasia 2008, 10:266-278. 2259455, 18320071.
65. Chik F, Szyf M. Effects of specific DNMT gene depletion on cancer cell transformation and breast cancer cell invasion; toward selective DNMT inhibitors. Carcinogenesis 2011, 32:224-232. 10.1093/carcin/bgq221, 20980350.
66. Dickinson RE, Dallol A, Bieche I, Krex D, Morton D, Maher ER, Latif F. Epigenetic inactivation of SLIT3 and SLIT1 genes in human cancers. Br J Cancer 2004, 91:2071-2078. 10.1038/sj.bjc.6602222, 2409788, 15534609.
67. Berman H, Zhang J, Crawford YG, Gauthier ML, Fordyce CA, McDermott KM, Sigaroudinia M, Kozakiewicz K, Tlsty TD. Genetic and epigenetic changes in mammary epithelial cells identify a subpopulation of cells involved in early carcinogenesis. Cold Spring Harb Symp Quant Biol 2005, 70:317-327. 10.1101/sqb.2005.70.051, 16869768.
68. Shinozaki M, Hoon DS, Giuliano AE, Hansen NM, Wang HJ, Turner R, Taback B. Distinct hypermethylation profile of primary breast cancer is associated with sentinel lymph node metastasis. Clin Cancer Res 2005, 11:2156-2162. 10.1158/1078-0432.CCR-04-1810, 15788661.
69. Woelfle U, Cloos J, Sauter G, Riethdorf L, Jänicke F, van Diest P, Brakenhoff R, Pantel K. Molecular signature associated with bone marrow micrometastasis in human breast cancer. Cancer Res 2003, 63:5679-5684.
70. Hedenfalk I, Duggan D, Chen Y, Radmacher M, Bittner M, Simon R, Meltzer P, Gusterson B, Esteller M, Kallioniemi OP, Wilfond B, Borg A, Trent J, Raffeld M, Yakhini Z, Ben-Dor A, Dougherty E, Kononen J, Bubendorf L, Fehrle W, Pittaluga S, Gruvberger S, Loman N, Johannsson O, Olsson H, Sauter G. Gene-expression profiles in hereditary breast cancer. N Engl J Med 2001, 344:539-548. 10.1056/NEJM200102223440801, 11207349.
71. Yan PS, Perry MR, Laux DE, Asare AL, Caldwell CW, Huang TH. CpG island arrays: an application toward deciphering epigenetic signatures of breast cancer. Clin Cancer Res 2000, 6:1432-1438.
72. Pakneshan P, Szyf M, Rabbani SA. Hypomethylation of urokinase (uPA) promoter in breast and prostate cancer: prognostic and therapeutic implications. Curr Cancer Drug Targets 2005, 5:471-488. 10.2174/156800905774574011, 16305345.
73. Szyf M, Pakneshan P, Rabbani SA. DNA methylation and breast cancer. Biochem Pharmacol 2004, 68:1187-1197. 10.1016/j.bcp.2004.04.030, 15313416.
74. Stefanska B, Huang J, Bhattacharyya B, Suderman M, Hallett M, Han ZG, Szyf M. Definition of the landscape of promoter DNA hypomethylation in liver cancer. Cancer Res 2011, 71:5891-5903. 10.1158/0008-5472.CAN-10-3823, 21747116.
75. Shi H, Yan PS, Chen CM, Rahmatpanah F, Lofton-Day C, Caldwell CW, Huang TH. Expressed CpG island sequence tag microarray for dual screening of DNA hypermethylation and gene silencing in cancer cells. Cancer Res 2002, 62:3214-3220.
76. Jiemjit A, Fandy TE, Carraway H, Bailey KA, Baylin S, Herman JG, Gore SD. p21(WAF1/CIP1) induction by 5-azacytosine nucleosides requires DNA damage. Oncogene 2008, 27:3615-3623. 10.1038/sj.onc.1211018, 18223691.
77. Bork S, Pfister S, Witt H, Horn P, Korn B, Ho AD, Wagner W. DNA methylation pattern changes upon long-term culture and aging of human mesenchymal stromal cells. Aging Cell 2010, 9:54-63. 10.1111/j.1474-9726.2009.00535.x, 2814091, 19895632.
78. Grafodatskaya D, Choufani S, Ferreira JC, Butcher DT, Lou Y, Zhao C, Scherer SW, Weksberg R. EBV transformation and cell culturing destabilizes DNA methylation in human lymphoblastoid cell lines. Genomics 2010, 95:73-83. 10.1016/j.ygeno.2009.12.001, 20005943.
79. Fu X, Deng H, Zhao L, Li J, Zhou Y, Zhang Y. Distinct expression patterns of hedgehog ligands between cultured and primary colorectal cancers are associated with aberrant methylation of their promoters. Mol Cell Biochem 2010, 337:185-192. 10.1007/s11010-009-0298-8, 19856079.
80. Fang F, Turcan S, Rimner A, Kaufman A, Giri D, Morris LG, Shen R, Seshan V, Mo Q, Heguy A, Baylin SB, Ahuja N, Viale A, Massague J, Norton L, Vahdat LT, Moynahan ME, Chan TA. Breast cancer methylomes establish an epigenomic foundation for metastasis. Sci Transl Med 2011, 3:75ra25. 10.1126/scitranslmed.3001875, 3146366, 21430268.
81. Andrews J, Kennette W, Pilon J, Hodgson A, Tuck AB, Chambers AF, Rodenhiser DI. Multi-platform whole-genome microarray analyses refine the epigenetic signature of breast cancer metastasis with gene expression and copy number. PLoS One 2010, 5:e8665. 10.1371/journal.pone.0008665, 2801616, 20084286.
82. Sun Z, Asmann YW, Kalari KR, Bot B, Eckel-Passow JE, Baker TR, Carr JM, Khrebtukova I, Luo S, Zhang L, Schroth GP, Perez EA, Thompson EA. Integrated analysis of gene expression, CpG island methylation, and gene copy number in breast cancer cells by deep sequencing. PLoS One 2011, 6:e17490. 10.1371/journal.pone.0017490, 3045451, 21364760.
83. Park SY, Kwon HJ, Choi Y, Lee HE, Kim SW, Kim JH, Kim IA, Jung N, Cho NY, Kang GH. Distinct patterns of promoter CpG island methylation of breast cancer subtypes are associated with stem cell phenotypes. Mod Pathol 2012, 25:185-196.
84. Keshet I, Schlesinger Y, Farkash S, Rand E, Hecht M, Segal E, Pikarski E, Young RA, Niveleau A, Cedar H, Simon I. Evidence for an instructive mechanism of de novo methylation in cancer cells. Nat Genet 2006, 38:149-153. 10.1038/ng1719, 16444255.
85. Ruike Y, Imanaka Y, Sato F, Shimizu K, Tsujimoto G. Genome-wide analysis of aberrant methylation in human breast cancer cells using methyl-DNA immunoprecipitation combined with high-throughput sequencing. BMC Genomics 2010, 11:137. 10.1186/1471-2164-11-137, 2838848, 20181289.
86. Bibikova M, Barnes B, Tsan C, Ho V, Klotzle B, Le JM, Delano D, Zhang L, Schroth GP, Gunderson KL, Fan JB, Shen R. High density DNA methylation array with single CpG site resolution. Genomics 2011, 98:288-295. 10.1016/j.ygeno.2011.07.007, 21839163.
87. Li L, Lee KM, Han W, Choi JY, Lee JY, Kang GH, Park SK, Noh DY, Yoo KY, Kang D. Estrogen and progesterone receptor status affect genome-wide DNA methylation profile in breast cancer. Hum Mol Genet 2010, 19:4273-4277. 10.1093/hmg/ddq351, 20724461.
88. Hill VK, Ricketts C, Bieche I, Vacher S, Gentle D, Lewis C, Maher ER, Latif F. Genome-wide DNA methylation profiling of CpG islands in breast cancer identifies novel genes associated with tumorigenicity. Cancer Res 2011, 71:2988-2999. 10.1158/0008-5472.CAN-10-4026, 21363912.
89. Toyota M, Ahuja N, Ohe-Toyota M, Herman JG, Baylin SB, Issa JP. CpG island methylator phenotype in colorectal cancer. Proc Natl Acad Sci USA 1999, 96:8681-8686. 10.1073/pnas.96.15.8681, 17576, 10411935.
90. Campbell PM, Bovenzi V, Szyf M. Methylated DNA-binding protein 2 antisense inhibitors suppress tumourigenesis of human cancer cell lines in vitro and in vivo. Carcinogenesis 2004, 25:499-507.
91. Szyf M. Epigenetics, DNA methylation, and chromatin modifying drugs. Annu Rev Pharmacol Toxicol 2009, 49:243-263. 10.1146/annurev-pharmtox-061008-103102, 18851683.
92. Chik F, Szyf M. Effects of specific DNMT gene depletion on cancer cell transformation and breast cancer cell invasion; toward selective DNMT inhibitors. Carcinogenesis 2011, 32:224-232. 10.1093/carcin/bgq221, 20980350.
93. Dedeurwaerder S, Desmedt C, Calonne E, Singhal SK, Haibe-Kains B, Defrance M, Michiels S, Volkmar M, Deplus R, Luciani J, Lallemand F, Larsimont D, Toussaint J, Haussy S, Rothé F, Rouas G, Metzger O, Majjaj S, Saini K, Putmans P, Hames G, van Baren N, Coulie PG, Piccart M, Sotiriou C, Fuks F. DNA methylation profiling reveals a predominant immune component in breast cancers. EMBO Mol Med 2011, 3:726-741. 10.1002/emmm.201100801, 21910250.
94. Dedeurwaerder S, Fumagalli D, Fuks F. Unravelling the epigenomic dimension of breast cancers. Curr Opin Oncol 2011, 23:559-565. 10.1097/CCO.0b013e32834bd481, 21946247.
95. Jing F, Yuping W, Yong C, Jie L, Jun L, Xuanbing T, Lihua H. CpG island methylator phenotype of multigene in serum of sporadic breast carcinoma. Tumour Biol 2010, 31:321-331. 10.1007/s13277-010-0040-x, 20490964.
96. Radpour R, Barekati Z, Kohler C, Lv Q, Bürki N, Diesch C, Bitzer J, Zheng H, Schmid S, Zhong XY. Hypermethylation of tumor suppressor genes involved in critical regulatory pathways for developing a blood-based test in breast cancer. PLoS One 2011, 6:e16080. 10.1371/journal.pone.0016080, 3025923, 21283676.
97. Prat A, Perou CM. Deconstructing the molecular portraits of breast cancer. Mol Oncol 2011, 5:5-23. 10.1016/j.molonc.2010.11.003, 21147047.
98. Finak G, Bertos N, Pepin F, Sadekova S, Souleimanova M, Zhao H, Chen H, Omeroglu G, Meterissian S, Omeroglu A, Hallett M, Park M. Stromal gene expression predicts clinical outcome in breast cancer. Nat Med 2008, 14:518-527. 10.1038/nm1764, 18438415.
99. Hu Z, Fan C, Oh DS, Marron JS, He X, Qaqish BF, Livasy C, Carey LA, Reynolds E, Dressler L, Nobel A, Parker J, Ewend MG, Sawyer LR, Wu J, Liu Y, Nanda R, Tretiakova M, Ruiz Orrico A, Dreher D, Palazzo JP, Perreard L, Nelson E, Mone M, Hansen H, Mullins M, Quackenbush JF, Ellis MJ, Olopade OI, Bernard PS, et al. The molecular portraits of breast tumors are conserved across microarray platforms. BMC Genomics 2006, 7:96. 10.1186/1471-2164-7-96, 1468408, 16643655.
100. Weigelt B, Hu Z, He X, Livasy C, Carey LA, Ewend MG, Glas AM, Perou CM, Van't Veer LJ. Molecular portraits and 70-gene prognosis signature are preserved throughout the metastatic process of breast cancer. Cancer Res 2005, 65:9155-9158. 10.1158/0008-5472.CAN-05-2553, 16230372.
101. Sørlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, van de Rijn M, Jeffrey SS, Thorsen T, Quist H, Matese JC, Brown PO, Botstein D, Eystein Lønning P, Børresen-Dale AL. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA 2001, 98:10869-10874. 10.1073/pnas.191367098, 58566, 11553815.
102. Perou CM, Sørlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lønning PE, Børresen-Dale AL, Brown PO, Botstein D. Molecular portraits of human breast tumours. Nature 2000, 406:747-752. 10.1038/35021093, 10963602.
103. Cedar H, Solage A, Glaser G, Razin A. Direct detection of methylated cytosine in DNA by use of the restriction enzyme MspI. Nucleic Acids Res 1979, 6:2125-2132. 10.1093/nar/6.6.2125, 327840, 223125.
104. Frommer M, McDonald LE, Millar DS, Collis CM, Watt F, Grigg GW, Molloy PL, Paul CL. A genomic sequencing protocol that yields a positive display of 5-methylcytosine residues in individual DNA strands. Proc Natl Acad Sci USA 1992, 89:1827-1831. 10.1073/pnas.89.5.1827, 48546, 1542678.
105. Clark SJ, Harrison J, Paul CL, Frommer M. High sensitivity mapping of methylated cytosines. Nucleic Acids Res 1994, 22:2990-2997. 10.1093/nar/22.15.2990, 310266, 8065911.
106. Brinkman AB, Simmer F, Ma K, Kaan A, Zhu J, Stunnenberg HG. Whole-genome DNA methylation profiling using MethylCap-seq. Methods 2010, 52:232-236. 10.1016/j.ymeth.2010.06.012, 20542119.
107. 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. High-throughput DNA methylation profiling using universal bead arrays. Genome Res 2006, 16:383-393. 10.1101/gr.4410706, 1415217, 16449502.
108. Dedeurwaerder S, Defrance M, Calonne E, Denis H, Sotiriou C, Fuks F. Evaluation of the Infinium Methylation 450 K technology. Epigenomics 2011, 3:771-784. 10.2217/epi.11.105, 22126295.
109. Shen L, Guo Y, Chen X, Ahmed S, Issa JP. Optimizing annealing temperature overcomes bias in bisulfite PCR methylation analysis. Biotechniques 2007, 42:48. 50, 52 passim, 10.2144/000112312, 17269485.