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Epigenomic Biomarkers for the Advance of Personalized Medicine

  • Chapter
Computational and Statistical Epigenomics

Part of the book series: Translational Bioinformatics ((TRBIO,volume 7))

Abstract

Epigenetic factors (DNA methylation, histone modifications, or ncRNAs) are involved in gene expression regulation. Thus, determining abnormal epigenetic changes is a suitable approach to extract meaningful information about human diseases. An altered pattern of epigenetic modifications has been firstly defined as a hallmark for cancer, although it is also a key element to many common human diseases, such as cardiovascular, metabolic, and neurological pathologies. During the last decade, the advent of genome-scale analysis techniques applied to epigenetics has provided a massive amount of data, enabling an important advance in the molecular mechanisms underlying disease initiation, progression, and expansion. Disease-specific epigenomic signatures, mainly based on DNA methylation analysis, have been studied for several clinical purposes including prognostics and diagnostics, as well as disease-specific chemotherapy response. Using noninvasive specimens, epigenetic profiling holds the promise of being of clinical value in the management of patients, even at the early stages of disease. Additionally, epigenetic marks have also been catalogued as targets for pharmacological drugs. The upgrade of epigenetic research to epigenomics together with other –omics would tackle the many unanswered questions in the field, paving the path to achieve a more precise personalized medicine.

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Bibliography

  • Ahlquist DA, Zou H, Domanico M, Mahoney DW, Yab TC, Taylor WR, Butz ML, Thibodeau SN, Rabeneck L, Paszat LF, Kinzler KW, Vogelstein B, Bjerregaard NC, Laurberg S, Sørensen HT, Berger BM, Lidgard GP. Next-generation stool DNA test accurately detects colorectal cancer and large adenomas. Gastroenterology. 2012a;142(2):248–56.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Ahlquist DA, Taylor WR, Mahoney DW, Zou H, Domanico M, Thibodeau SN, Boardman LA, Berger BM, Lidgard GP. The stool DNA test is more accurate than the plasma septin 9 test in detecting colorectal neoplasia. Clin Gastroenterol Hepatol. 2012b;10(3):272–7.e1.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Ang PW, Loh M, Liem N, Lim PL, Grieu F, Vaithilingam A, Platell C, Yong WP, Iacopetta B, Soong R. Comprehensive profiling of DNA methylation in colorectal cancer reveals subgroups with distinct clinicopathological and molecular features. BMC Cancer. 2010;10:227.

    PubMed Central  PubMed  Google Scholar 

  • Aslibekyan S, Claas SA, Arnett DK. Clinical applications of epigenetics in cardiovascular disease: the long road ahead. Transl Res. 2015;165(1):143–53. pii: S1931-5244(14)00128-5.

    CAS  PubMed  Google Scholar 

  • Baba Y, Nosho K, Shima K, Huttenhower C, Tanaka N, Hazra A, Giovannucci EL, Fuchs CS, Ogino S. Hypomethylation of the IGF2 DMR in colorectal tumors, detected by bisulfite pyrosequencing, is associated with poor prognosis. Gastroenterology. 2010;139(6):1855–64.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Bakulski KM, Dolinoy DC, Sartor MA, Paulson HL, Konen JR, Lieberman AP, Albin RL, Hu H, Rozek LS. Genome-wide DNA methylation differences between late-onset Alzheimer’s disease and cognitively normal controls in human frontal cortex. J Alzheimers Dis. 2012;29(3):571–88.

    CAS  PubMed  Google Scholar 

  • Balaguer F, Link A, Lozano JJ, Cuatrecasas M, Nagasaka T, Boland CR, Goel A. Epigenetic silencing of miR-137 is an early event in colorectal carcinogenesis. Cancer Res. 2010;70(16):6609–18.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Barski A, Cuddapah S, Cui K, Roh TY, Schones DE, Wang Z, Wei G, Chepelev I, Zhao K. High-resolution profiling of histone methylations in the human genome. Cell. 2007;129(4):823–37.

    CAS  PubMed  Google Scholar 

  • Bean GR, Bryson AD, Pilie PG, Goldenberg V, Baker Jr JC, Ibarra C, Brander DM, Paisie C, Case NR, Gauthier M, Reynolds PA, Dietze E, Ostrander J, Scott V, Wilke LG, Yee L, Kimler BF, Fabian CJ, Zalles CM, Broadwater G, Tlsty TD, Seewaldt VL. Morphologically normal-appearing mammary epithelial cells obtained from high-risk women exhibit methylation silencing of INK4a/ARF. Clin Cancer Res. 2007;13(22 Pt 1):6834–41.

    CAS  PubMed  Google Scholar 

  • Belinsky SA. Silencing of genes by promoter hypermethylation: key event in rodent and human lung cancer. Carcinogenesis. 2005;26(9):1481–7.

    CAS  PubMed  Google Scholar 

  • Belinsky SA, Klinge DM, Dekker JD, Smith MW, Bocklage TJ, Gilliland FD, Crowell RE, Karp DD, Stidley CA, Picchi MA. Gene promoter methylation in plasma and sputum increases with lung cancer risk. Clin Cancer Res. 2005;11(18):6505–11.

    CAS  PubMed  Google Scholar 

  • Belinsky SA, Grimes MJ, Casas E, Stidley CA, Franklin WA, Bocklage TJ, Johnson DH, Schiller JH. Predicting gene promoter methylation in non-small cell lung cancer by evaluating sputum and serum. Br J Cancer. 2007;96(8):1278–83.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Berghmans T, Ameye L, Willems L, Paesmans M, Mascaux C, Lafitte JJ, Meert AP, Scherpereel A, Cortot AB, Cstoth I, Dernies T, Toussaint L, Leclercq N, Sculier JP, European Lung Cancer Working Party. Identification of microRNA-based signatures for response and survival for non-small cell lung cancer treated with cisplatin-vinorelbine A ELCWP prospective study. Lung Cancer. 2013;82(2):340–5.

    CAS  PubMed  Google Scholar 

  • 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;70:317–27.

    CAS  PubMed  Google Scholar 

  • 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(3):383–93.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Bock C. Analysing and interpreting DNA methylation data. Nat Rev Genet. 2012;13(10):705–19.

    CAS  PubMed  Google Scholar 

  • Breitling LP, Salzmann K, Rothenbacher D, Burwinkel B, Brenner H. Smoking, F2RL3 methylation, and prognosis in stable coronary heart disease. Eur Heart J. 2012;33(22):2841–8.

    CAS  PubMed  Google Scholar 

  • Brock MV, Hooker CM, Ota-Machida E, Han Y, Guo M, Ames S, Glöckner S, Piantadosi S, Gabrielson E, Pridham G, Pelosky K, Belinsky SA, Yang SC, Baylin SB, Herman JG. DNA methylation markers and early recurrence in stage I lung cancer. N Engl J Med. 2008;358(11):1118–28.

    CAS  PubMed  Google Scholar 

  • Brooks J, Cairns P, Zeleniuch-Jacquotte A. Promoter methylation and the detection of breast cancer. Cancer Causes Control. 2009;20(9):1539–50.

    PubMed Central  PubMed  Google Scholar 

  • 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(4):499–507.

    CAS  PubMed  Google Scholar 

  • Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature. 2012;490(7418):61–70.

    Google Scholar 

  • Chekhun VF, Kulik GI, Yurchenko OV, Tryndyak VP, Todor IN, Luniv LS, Tregubova NA, Pryzimirska TV, Montgomery B, Rusetskaya NV, Pogribny IP. Role of DNA hypomethylation in the development of the resistance to doxorubicin in human MCF-7 breast adenocarcinoma cells. Cancer Lett. 2006;231(1):87–93.

    CAS  PubMed  Google Scholar 

  • Cho YH, Shen J, Gammon MD, Zhang YJ, Wang Q, Gonzalez K, Xu X, Bradshaw PT, Teitelbaum SL, Garbowski G, Hibshoosh H, Neugut AI, Chen J, Santella RM. Prognostic significance of gene-specific promoter hypermethylation in breast cancer patients. Breast Cancer Res Treat. 2012;131(1):197–205.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Cortessis VK, Thomas DC, Levine AJ, Breton CV, Mack TM, Siegmund KD, Haile RW, Laird PW. Environmental epigenetics: prospects for studying epigenetic mediation of exposure-response relationships. Hum Genet. 2012;131(10):1565–89.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Dave B, Mittal V, Tan NM, Chang JC. Epithelial-mesenchymal transition, cancer stem cells and treatment resistance. Breast Cancer Res. 2012;14(1):202.

    PubMed Central  PubMed  Google Scholar 

  • 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(12):726–41.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Dejeux E, Rønneberg JA, Solvang H, Bukholm I, Geisler S, Aas T, Gut IG, Børresen-Dale AL, Lønning PE, Kristensen VN, Tost J. DNA methylation profiling in doxorubicin treated primary locally advanced breast tumours identifies novel genes associated with survival and treatment response. Mol Cancer. 2010;9:68.

    PubMed Central  PubMed  Google Scholar 

  • deVos T, Tetzner R, Model F, Weiss G, Schuster M, Distler J, Steiger KV, Grützmann R, Pilarsky C, Habermann JK, Fleshner PR, Oubre BM, Day R, Sledziewski AZ, Lofton-Day C. Circulating methylated SEPT9 DNA in plasma is a biomarker for colorectal cancer. Clin Chem. 2009;55(7):1337–46.

    CAS  PubMed  Google Scholar 

  • Dietrich D, Kneip C, Raji O, Liloglou T, Seegebarth A, Schlegel T, Flemming N, Rausch S, Distler J, Fleischhacker M, Schmidt B, Giles T, Walshaw M, Warburton C, Liebenberg V, Field JK. Performance evaluation of the DNA methylation biomarker SHOX2 for the aid in diagnosis of lung cancer based on the analysis of bronchial aspirates. Int J Oncol. 2012;40(3):825–32.

    CAS  PubMed  Google Scholar 

  • Dulaimi E, Hillinck J, Ibanez de Caceres I, Al-Saleem T, Cairns P. Tumor suppressor gene promoter hypermethylation in serum of breast cancer patients. Clin Cancer Res. 2004;10(18 Pt 1):6189–93.

    CAS  PubMed  Google Scholar 

  • Dumenil TD, Wockner LF, Bettington M, McKeone DM, Klein K, Bowdler LM, Montgomery GW, Leggett BA, Whitehall VL. Genome-wide DNA methylation analysis of formalin-fixed paraffin embedded colorectal cancer tissue. Genes Chromosomes Cancer. 2014;53(7):537–48.

    CAS  PubMed  Google Scholar 

  • Elsheikh SE, Green AR, Rakha EA, Powe DG, Ahmed RA, Collins HM, Soria D, Garibaldi JM, Paish CE, Ammar AA, Grainge MJ, Ball GR, Abdelghany MK, Martinez-Pomares L, Heery DM, Ellis IO. Global histone modifications in breast cancer correlate with tumor phenotypes, prognostic factors, and patient outcome. Cancer Res. 2009;69(9):3802–9.

    CAS  PubMed  Google Scholar 

  • Estécio MR, Gharibyan V, Shen L, Ibrahim AE, Doshi K, He R, Jelinek J, Yang AS, Yan PS, Huang TH, Tajara EH, Issa JP. LINE-1 hypomethylation in cancer is highly variable and inversely correlated with microsatellite instability. PLoS One. 2007;2(5):e399.

    PubMed Central  PubMed  Google Scholar 

  • Esteller M. Epigenetics in cancer. N Engl J Med. 2008;358(11):1148–59.

    CAS  PubMed  Google Scholar 

  • Esteller M, Sanchez-Cespedes M, Rosell R, Sidransky D, Baylin SB, Herman JG. Detection of aberrant promoter hypermethylation of tumor suppressor genes in serum DNA from non-small cell lung cancer patients. Cancer Res. 1999a;59(1):67–70.

    CAS  PubMed  Google Scholar 

  • Esteller M, Hamilton SR, Burger PC, Baylin SB, Herman JG. Inactivation of the DNA repair gene O6-methylguanine-DNA methyltransferase by promoter hypermethylation is a common event in primary human neoplasia. Cancer Res. 1999b;59(4):793–7.

    CAS  PubMed  Google Scholar 

  • Esteller M, Garcia-Foncillas J, Andion E, Goodman SN, Hidalgo OF, Vanaclocha V, Baylin SB, Herman JG. Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. N Engl J Med. 2000;343(19):1350–4.

    CAS  PubMed  Google Scholar 

  • 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. DNA methylation patterns in hereditary human cancers mimic sporadic tumorigenesis. Hum Mol Genet. 2001;10(26):3001–7.

    CAS  PubMed  Google Scholar 

  • Fackler MJ, Umbricht CB, Williams D, Argani P, Cruz LA, Merino VF, Teo WW, Zhang Z, Huang P, Visvananthan K, Marks J, Ethier S, Gray JW, Wolff AC, Cope LM, Sukumar S. Genome-wide methylation analysis identifies genes specific to breast cancer hormone receptor status and risk of recurrence. Cancer Res. 2011;71(19):6195–207.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Fackler MJ, Lopez Bujanda Z, Umbricht C, Teo WW, Cho S, Zhang Z, Visvanathan K, Jeter S, Argani P, Wang C, Lyman JP, de Brot M, Ingle JN, Boughey J, McGuire K, King TA, Carey LA, Cope L, Wolff AC, Sukumar S. Novel methylated biomarkers and a robust assay to detect circulating tumor DNA in metastatic breast cancer. Cancer Res. 2014;74(8):2160–70.

    PubMed Central  CAS  PubMed  Google Scholar 

  • 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(75):75ra25.

    PubMed Central  PubMed  Google Scholar 

  • Felip E, Martinez P. Can sensitivity to cytotoxic chemotherapy be predicted by biomarkers? Ann Oncol. 2012;23 Suppl 10:x189–92.

    Google Scholar 

  • Flanagan JM, Cocciardi S, Waddell N, Johnstone CN, Marsh A, Henderson S, Simpson P, da Silva L; kConFab Investigators, 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(3):420–33.

    Google Scholar 

  • Foekens JA, Sieuwerts AM, Smid M, Look MP, de Weerd V, Boersma AW, Klijn JG, Wiemer EA, Martens JW. Four miRNAs associated with aggressiveness of lymph node-negative, estrogen receptor-positive human breast cancer. Proc Natl Acad Sci U S A. 2008;105(35):13021–6.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Fong PC, Boss DS, Yap TA, Tutt A, Wu P, Mergui-Roelvink M, Mortimer P, Swaisland H, Lau A, O’Connor MJ, Ashworth A, Carmichael J, Kaye SB, Schellens JH, de Bono JS. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med. 2009;361(2):123–34.

    CAS  PubMed  Google Scholar 

  • Gall TM, Frampton AE, Krell J, Castellano L, Stebbing J, Jiao LR. Blood-based miRNAs as noninvasive diagnostic and surrogative biomarkers in colorectal cancer. Expert Rev Mol Diagn. 2013;13(2):141–5.

    CAS  PubMed  Google Scholar 

  • García-Giménez JL, Sanchis-Gomar F, Lippi G, Mena S, Ivars D, Gomez-Cabrera MC, Viña J, Pallardó FV. Epigenetic biomarkers: a new perspective in laboratory diagnostics. Clin Chim Acta. 2012;413(19–20):1576–82.

    PubMed  Google Scholar 

  • Gargalionis AN, Basdra EK. Insights in microRNAs biology. Curr Top Med Chem. 2013;13(13):1493–502.

    CAS  PubMed  Google Scholar 

  • Garzon R, Marcucci G, Croce CM. Targeting microRNAs in cancer: rationale, strategies, and challenges. Nat Rev Drug Discov. 2010;9(10):775–89.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Gezer U, Ustek D, Yörüker EE, Cakiris A, Abaci N, Leszinski G, Dalay N, Holdenrieder S. Characterization of H3K9me3- and H4K20me3-associated circulating nucleosomal DNA by high-throughput sequencing in colorectal cancer. Tumour Biol. 2013;34(1):329–36.

    CAS  PubMed  Google Scholar 

  • Goate A, Chartier-Harlin MC, Mullan M, Brown J, Crawford F, Fidani L, Giuffra L, Haynes A, Irving N, James L. Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer’s disease. Nature. 1991;349(6311):704–6.

    CAS  PubMed  Google Scholar 

  • Grady WM, Carethers JM. Genomic and epigenetic instability in colorectal cancer pathogenesis. Gastroenterology. 2008;135(4):1079–99.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Guay SP, Voisin G, Brisson D, Munger J, Lamarche B, Gaudet D, Bouchard L. Epigenome-wide analysis in familial hypercholesterolemia identified new loci associated with high-density lipoprotein cholesterol concentration. Epigenomics. 2012;4(6):623–39.

    CAS  PubMed  Google Scholar 

  • He L, Hannon GJ. MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet. 2004;5(7):522–31.

    CAS  PubMed  Google Scholar 

  • Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, Bromberg JE, Hau P, Mirimanoff RO, Cairncross JG, Janzer RC, Stupp R. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005;352(10):997–1003.

    CAS  PubMed  Google Scholar 

  • Heller G, Babinsky VN, Ziegler B, Weinzierl M, Noll C, Altenberger C, Müllauer L, Dekan G, Grin Y, Lang G, End-Pfützenreuter A, Steiner I, Zehetmayer S, Döme B, Arns BM, Fong KM, Wright CM, Yang IA, Klepetko W, Posch M, Zielinski CC, Zöchbauer-Müller S. Genome-wide CpG island methylation analyses in non-small cell lung cancer patients. Carcinogenesis. 2013;34(3):513–21.

    CAS  PubMed  Google Scholar 

  • Henschke CI, Yankelevitz DF, Libby DM, Pasmantier MW, Smith JP, Miettinen OS. Survival of patients with stage I lung cancer detected on CT screening. N Engl J Med. 2006;355(17):1763–71.

    PubMed  Google Scholar 

  • Herbst A, Wallner M, Rahmig K, Stieber P, Crispin A, Lamerz R, Kolligs FT. Methylation of helicase-like transcription factor in serum of patients with colorectal cancer is an independent predictor of disease recurrence. Eur J Gastroenterol Hepatol. 2009;21(5):565–9.

    CAS  PubMed  Google Scholar 

  • Heyn H, Esteller M. DNA methylation profiling in the clinic: applications and challenges. Nat Rev Genet. 2012;13(10):679–92.

    CAS  PubMed  Google Scholar 

  • Heyn H, Méndez-González J, Esteller M. Epigenetic profiling joins personalized cancer medicine. Expert Rev Mol Diagn. 2013a;13(5):473–9.

    CAS  PubMed  Google Scholar 

  • Heyn H, Carmona FJ, Gomez A, Ferreira HJ, Bell JT, Sayols S, Ward K, Stefansson OA, Moran S, Sandoval J, Eyfjord JE, Spector TD, Esteller M. DNA methylation profiling in breast cancer discordant identical twins identifies DOK7 as novel epigenetic biomarker. Carcinogenesis. 2013b;34(1):102–8.

    PubMed Central  CAS  PubMed  Google Scholar 

  • 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(8):2988–99.

    CAS  PubMed  Google Scholar 

  • Hinoue T, Weisenberger DJ, Pan F, Campan M, Kim M, Young J, Whitehall VL, Leggett BA, Laird PW. Analysis of the association between CIMP and BRAF in colorectal cancer by DNA methylation profiling. PLoS One. 2009;4(12):e8357.

    PubMed Central  PubMed  Google Scholar 

  • Hinoue T, Weisenberger DJ, Lange CP, Shen H, Byun HM, Van Den Berg D, Malik S, Pan F, Noushmehr H, van Dijk CM, Tollenaar RA, Laird PW. Genome-scale analysis of aberrant DNA methylation in colorectal cancer. Genome Res. 2012;22(2):271–82.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Hu XC, Wong IH, Chow LW. Tumor-derived aberrant methylation in plasma of invasive ductal breast cancer patients: clinical implications. Oncol Rep. 2003;10(6):1811–5.

    CAS  PubMed  Google Scholar 

  • Hughes LA, Khalid-de Bakker CA, Smits KM, van den Brandt PA, Jonkers D, Ahuja N, Herman JG, Weijenberg MP, van Engeland M. The CpG island methylator phenotype in colorectal cancer: progress and problems. Biochim Biophys Acta. 2012;1825(1):77–85.

    CAS  PubMed  Google Scholar 

  • Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, Magri E, Pedriali M, Fabbri M, Campiglio M, Ménard S, Palazzo JP, Rosenberg A, Musiani P, Volinia S, Nenci I, Calin GA, Querzoli P, Negrini M, Croce CM. MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 2005;65(16):7065–70.

    CAS  PubMed  Google Scholar 

  • Iorio MV, Piovan C, Croce CM. Interplay between microRNAs and the epigenetic machinery: an intricate network. Biochim Biophys Acta. 2010;1799(10–12):694–701.

    CAS  PubMed  Google Scholar 

  • Iorio MV, Casalini P, Piovan C, Braccioli L, Tagliabue E. Breast cancer and microRNAs: therapeutic impact. Breast. 2011;20 Suppl 3:S63–70.

    PubMed  Google Scholar 

  • Jackson K, Yu MC, Arakawa K, Fiala E, Youn B, Fiegl H, Müller-Holzner E, Widschwendter M, Ehrlich M. DNA hypomethylation is prevalent even in low-grade breast cancers. Cancer Biol Ther. 2004;3(12):1225–31.

    CAS  PubMed  Google Scholar 

  • Jakovcevski M, Akbarian S. Epigenetic mechanisms in neurological disease. Nat Med. 2012;18(8):1194–204. doi:10.1038/nm.2828.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Jamaluddin MS, Yang X, Wang H. Hyperhomocysteinemia, DNA methylation and vascular disease. Clin Chem Lab Med. 2007;45(12):1660–6.

    CAS  PubMed  Google Scholar 

  • Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics, 2007. CA Cancer J Clin. 2007;57(1):43–66.

    PubMed  Google Scholar 

  • Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.

    PubMed  Google Scholar 

  • Jensen LH, Rasmussen AA, Byriel L, Kuramochi H, Crüger DG, Lindebjerg J, Danenberg PV, Jakobsen A, Danenberg K. Regulation of MLH1 mRNA and protein expression by promoter methylation in primary colorectal cancer: a descriptive and prognostic cancer marker study. Cell Oncol (Dordr). 2013;36(5):411–9.

    CAS  Google Scholar 

  • Johnson SM, Grosshans H, Shingara J, Byrom M, Jarvis R, Cheng A, Labourier E, Reinert KL, Brown D, Slack FJ. RAS is regulated by the let-7 microRNA family. Cell. 2005;120(5):635–47.

    CAS  PubMed  Google Scholar 

  • Johnson DS, Mortazavi A, Myers RM, Wold B. Genome-wide mapping of in vivo protein-DNA interactions. Science. 2007;316(5830):1497–502.

    CAS  PubMed  Google Scholar 

  • Juo YY, Johnston FM, Zhang DY, Juo HH, Wang H, Pappou EP, Yu T, Easwaran H, Baylin S, Engeland M, Ahuja N. Prognostic value of CpG island methylator phenotype among colorectal cancer patients: a systematic review and meta-analysis. Ann Oncol. 2014;25(12):2314–27. pii: mdu149.

    CAS  PubMed  Google Scholar 

  • Karpinski P, Walter M, Szmida E, Ramsey D, Misiak B, Kozlowska J, Bebenek M, Grzebieniak Z, Blin N, Laczmanski L, Sasiadek MM. Intermediate- and low-methylation epigenotypes do not correspond to CpG island methylator phenotype (low and -zero) in colorectal cancer. Cancer Epidemiol Biomarkers Prev. 2013;22(2):201–8.

    CAS  PubMed  Google Scholar 

  • Khamas A, Ishikawa T, Shimokawa K, Mogushi K, Iida S, Ishiguro M, Mizushima H, Tanaka H, Uetake H, Sugihara K. Screening for epigenetically masked genes in colorectal cancer using 5-Aza-2′-deoxycytidine, microarray, and gene expression profile. Cancer Genomics Proteomics. 2012;9(2):67–75.

    CAS  PubMed  Google Scholar 

  • Kibriya MG, Raza M, Jasmine F, Roy S, Paul-Brutus R, Rahaman R, Dodsworth C, Rakibuz-Zaman M, Kamal M, Ahsan H. A genome-wide DNA methylation study in colorectal carcinoma. BMC Med Genomics. 2011;4:50.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Kim T, Reitmair A. Non-coding RNAs: functional aspects and diagnostic utility in oncology. Int J Mol Sci. 2013;14(3):4934–68.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Kim YH, Lee HC, Kim SY, Yeom YI, Ryu KJ, Min BH, Kim DH, Son HJ, Rhee PL, Kim JJ, Rhee JC, Kim HC, Chun HK, Grady WM, Kim YS. Epigenomic analysis of aberrantly methylated genes in colorectal cancer identifies genes commonly affected by epigenetic alterations. Ann Surg Oncol. 2011;18(8):2338–47.

    PubMed Central  PubMed  Google Scholar 

  • Kratz JR, He J, Van Den Eeden SK, Zhu ZH, Gao W, Pham PT, Mulvihill MS, Ziaei F, Zhang H, Su B, Zhi X, Quesenberry CP, Habel LA, Deng Q, Wang Z, Zhou J, Li H, Huang MC, Yeh CC, Segal MR, Ray MR, Jones KD, Raz DJ, Xu Z, Jahan TM, Berryman D, He B, Mann MJ, Jablons DM. A practical molecular assay to predict survival in resected non-squamous, non-small cell lung cancer: development and international validation studies. Lancet. 2012;379(9818):823–32.

    PubMed Central  PubMed  Google Scholar 

  • Laird PW. Principles and challenges of genomewide DNA methylation analysis. Nat Rev Genet. 2010;11(3):191–203.

    CAS  PubMed  Google Scholar 

  • Lange CP, Campan M, Hinoue T, Schmitz RF, van der Meulen-de Jong AE, Slingerland H, Kok PJ, van Dijk CM, Weisenberger DJ, Shen H, Tollenaar RA, Laird PW. Genome-scale discovery of DNA-methylation biomarkers for blood-based detection of colorectal cancer. PLoS One. 2012;7(11):e50266.

    PubMed Central  CAS  PubMed  Google Scholar 

  • 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(21):4273–7.

    CAS  PubMed  Google Scholar 

  • Licchesi JD, Westra WH, Hooker CM, Herman JG. Promoter hypermethylation of hallmark cancer genes in atypical adenomatous hyperplasia of the lung. Clin Cancer Res. 2008;14(9):2570–8.

    CAS  PubMed  Google Scholar 

  • Liu WJ, Tan XH, Guo BP, Ke Q, Sun J, Cen H. Associations between RASSF1A promoter methylation and NSCLC: a meta-analysis of published data. Asian Pac J Cancer Prev. 2013;14(6):3719–24.

    PubMed  Google Scholar 

  • Lo PK, Sukumar S. Epigenomics and breast cancer. Pharmacogenomics. 2008;9(12):1879–902.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Locke I, Kote-Jarai Z, Fackler MJ, Bancroft E, Osin P, Nerurkar A, Izatt L, Pichert G, Gui GP, Eeles RA. Gene promoter hypermethylation in ductal lavage fluid from healthy BRCA gene mutation carriers and mutation-negative controls. Breast Cancer Res. 2007;9(1):R20.

    PubMed Central  PubMed  Google Scholar 

  • Lockwood WW, Wilson IM, Coe BP, Chari R, Pikor LA, Thu KL, Solis LM, Nunez MI, Behrens C, Yee J, English J, Murray N, Tsao MS, Minna JD, Gazdar AF, Wistuba II, MacAulay CE, Lam S, Lam WL. Divergent genomic and epigenomic landscapes of lung cancer subtypes underscore the selection of different oncogenic pathways during tumor development. PLoS One. 2012;7(5):e37775.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Lu C, Soria JC, Tang X, Xu XC, Wang L, Mao L, Lotan R, Kemp B, Bekele BN, Feng L, Hong WK, Khuri FR. Prognostic factors in resected stage I non-small cell lung cancer: a multivariate analysis of six molecular markers. J Clin Oncol. 2004;22(22):4575–83.

    PubMed  Google Scholar 

  • Lund G, Zaina S. Atherosclerosis: an epigenetic balancing act that goes wrong. Curr Atheroscler Rep. 2011;13(3):208–14.

    CAS  PubMed  Google Scholar 

  • Luo X, Stock C, Burwinkel B, Brenner H. Identification and evaluation of plasma microRNAs for early detection of colorectal cancer. PLoS One. 2013;8(5):e62880.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Luo Y, Wong CJ, Kaz AM, Dzieciatkowski S, Carter KT, Morris SM, Wang J, Willis JE, Makar KW, Ulrich CM, Lutterbaugh JD, Shrubsole MJ, Zheng W, Markowitz SD, Grady WM. Differences in DNA methylation signatures reveal multiple pathways of progression from adenoma to colorectal cancer. Gastroenterology. 2014;147(2):418–29.e8. pii: S0016-5085(14)00595-2.

    CAS  PubMed  Google Scholar 

  • Mastroeni D, McKee A, Grover A, Rogers J, Coleman PD. Epigenetic differences in cortical neurons from a pair of monozygotic twins discordant for Alzheimer’s disease. PLoS One. 2009;4(8):e6617.

    PubMed Central  PubMed  Google Scholar 

  • Mastroeni D, Grover A, Delvaux E, Whiteside C, Coleman PD, Rogers J. Epigenetic changes in Alzheimer’s disease: decrements in DNA methylation. Neurobiol Aging. 2010;31(12):2025–37.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Menigatti M, Truninger K, Gebbers JO, Marbet U, Marra G, Schär P. Normal colorectal mucosa exhibits sex- and segment-specific susceptibility to DNA methylation at the hMLH1 and MGMT promoters. Oncogene. 2009;28(6):899–909.

    CAS  PubMed  Google Scholar 

  • Mikeska T, Bock C, Do H, Dobrovic A. DNA methylation biomarkers in cancer: progress towards clinical implementation. Expert Rev Mol Diagn. 2012;12(5):473–87.

    CAS  PubMed  Google Scholar 

  • Morán A, Fernández-Marcelo T, Carro J, De Juan C, Pascua I, Head J, Gómez A, Hernando F, Torres AJ, Benito M, Iniesta P. Methylation profiling in non-small cell lung cancer: clinical implications. Int J Oncol. 2012;40(3):739–46.

    PubMed  Google Scholar 

  • Movassagh M, Choy MK, Knowles DA, Cordeddu L, Haider S, Down T, Siggens L, Vujic A, Simeoni I, Penkett C, Goddard M, Lio P, Bennett MR, Foo RS. Distinct epigenomic features in end-stage failing human hearts. Circulation. 2011;124(22):2411–22.

    PubMed Central  PubMed  Google Scholar 

  • Müller HM, Oberwalder M, Fiegl H, Morandell M, Goebel G, Zitt M, Mühlthaler M, Ofner D, Margreiter R, Widschwendter M. Methylation changes in faecal DNA: a marker for colorectal cancer screening? Lancet. 2004;363(9417):1283–5.

    PubMed  Google Scholar 

  • Müller BM, Jana L, Kasajima A, Lehmann A, Prinzler J, Budczies J, Winzer KJ, Dietel M, Weichert W, Denkert C. Differential expression of histone deacetylases HDAC1, 2, and 3 in human breast cancer–overexpression of HDAC2 and HDAC3 is associated with clinicopathological indicators of disease progression. BMC Cancer. 2013;13:215.

    PubMed Central  PubMed  Google Scholar 

  • Nakazawa T, Kondo T, Ma D, Niu D, Mochizuki K, Kawasaki T, Yamane T, Iino H, Fujii H, Katoh R. Global histone modification of histone H3 in colorectal cancer and its precursor lesions. Hum Pathol. 2012;43(6):834–42.

    CAS  PubMed  Google Scholar 

  • Nelson HH, Marsit CJ, Christensen BC, Houseman EA, Kontic M, Wiemels JL, Karagas MR, Wrensch MR, Zheng S, Wiencke JK, Kelsey KT. Key epigenetic changes associated with lung cancer development: results from dense methylation array profiling. Epigenetics. 2012;7(6):559–66.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Nilsson TK, Löf-Öhlin ZM, Sun XF. DNA methylation of the p14ARF, RASSF1A, and APC1A genes as an independent prognostic factor in colorectal cancer patients. Int J Oncol. 2013;42(1):127–33.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Oberwalder M, Zitt M, Wöntner C, Fiegl H, Goebel G, Zitt M, Köhle O, Mühlmann G, Ofner D, Margreiter R, Müller HM. SFRP2 methylation in fecal DNA–a marker for colorectal polyps. Int J Colorectal Dis. 2008;23(1):15–9.

    PubMed  Google Scholar 

  • Oster B, Thorsen K, Lamy P, Wojdacz TK, Hansen LL, Birkenkamp-Demtröder K, Sørensen KD, Laurberg S, Orntoft TF, Andersen CL. Identification and validation of highly frequent CpG island hypermethylation in colorectal adenomas and carcinomas. Int J Cancer. 2011;129(12):2855–66.

    CAS  PubMed  Google Scholar 

  • Oster B, Linnet L, Christensen LL, Thorsen K, Ongen H, Dermitzakis ET, Sandoval J, Moran S, Esteller M, Hansen TF, Lamy P; COLOFOL steering group, Laurberg S, Ørntoft TF, Andersen CL. Non-CpG island promoter hypomethylation and miR-149 regulate the expression of SRPX2 in colorectal cancer. Int J Cancer. 2013;132(10):2303–15.

    Google Scholar 

  • 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(30):31735–44.

    CAS  PubMed  Google Scholar 

  • Paneni F, Costantino S, Volpe M, Lüscher TF, Cosentino F. Epigenetic signatures and vascular risk in type 2 diabetes: a clinical perspective. Atherosclerosis. 2013;230(2):191–7.

    CAS  PubMed  Google Scholar 

  • Park J, Brena RM, Gruidl M, Zhou J, Huang T, Plass C, Tockman MS. CpG island hypermethylation profiling of lung cancer using restriction landmark genomic scanning (RLGS) analysis. Cancer Biomark. 2005;1(2–3):193–200.

    CAS  PubMed  Google Scholar 

  • Park JY, Kim D, Yang M, Park HY, Lee SH, Rincon M, Kreahling J, Plass C, Smiraglia DJ, Tockman MS, Kim SJ. Gene silencing of SLC5A8 identified by genome-wide methylation profiling in lung cancer. Lung Cancer. 2013;79(3):198–204.

    PubMed Central  PubMed  Google Scholar 

  • Patnaik SK, Kannisto E, Knudsen S, Yendamuri S. Evaluation of microRNA expression profiles that may predict recurrence of localized stage I non-small cell lung cancer after surgical resection. Cancer Res. 2010;70:36–45.

    CAS  PubMed  Google Scholar 

  • Perkins E, Murphy SK, Murtha AP, Schildkraut J, Jirtle RL, Demark-Wahnefried W, Forman MR, Kurtzberg J, Overcash F, Huang Z, Hoyo C. Insulin-like growth factor 2/H19 methylation at birth and risk of overweight and obesity in children. J Pediatr. 2012;161(1):31–9.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Pignon JP, Tribodet H, Scagliotti GV, Douillard JY, Shepherd FA, Stephens RJ, Dunant A, Torri V, Rosell R, Seymour L, Spiro SG, Rolland E, Fossati R, Aubert D, Ding K, Waller D, Le Chevalier T, LACE Collaborative Group. Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative Group. J Clin Oncol. 2008;26(21):3552–9.

    PubMed  Google Scholar 

  • Potapova A, Hoffman AM, Godwin AK, Al-Saleem T, Cairns P. Promoter hypermethylation of the PALB2 susceptibility gene in inherited and sporadic breast and ovarian cancer. Cancer Res. 2008;68(4):998–1002.

    CAS  PubMed  Google Scholar 

  • Rao JS, Keleshian VL, Klein S, Rapoport SI. Epigenetic modifications in frontal cortex from Alzheimer’s disease and bipolar disorder patients. Transl Psychiatry. 2012;2:e132.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Raponi M, Dossey L, Jatkoe T, Wu X, Chen G, Fan H, Beer DG. MicroRNA classifiers for predicting prognosis of squamous cell lung cancer. Cancer Res. 2009;69:5776–6783.

    CAS  PubMed  Google Scholar 

  • Rauch TA, Zhong X, Wu X, Wang M, Kernstine KH, Wang Z, Riggs AD, Pfeifer GP. High-resolution mapping of DNA hypermethylation and hypomethylation in lung cancer. Proc Natl Acad Sci U S A. 2008;105(1):252–7.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Robertson AG, Bilenky M, Tam A, Zhao Y, Zeng T, Thiessen N, Cezard T, Fejes AP, Wederell ED, Cullum R, Euskirchen G, Krzywinski M, Birol I, Snyder M, Hoodless PA, Hirst M, Marra MA, Jones SJ. Genome-wide relationship between histone H3 lysine 4 mono- and tri-methylation and transcription factor binding. Genome Res. 2008;18(12):1906–17.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Sanchez-Mut JV, Aso E, Panayotis N, Lott I, Dierssen M, Rabano A, Urdinguio RG, Fernandez AF, Astudillo A, Martin-Subero JI, Balint B, Fraga MF, Gomez A, Gurnot C, Roux JC, Avila J, Hensch TK, Ferrer I, Esteller M. DNA methylation map of mouse and human brain identifies target genes in Alzheimer’s disease. Brain. 2013;136(Pt 10):3018–27.

    PubMed Central  PubMed  Google Scholar 

  • Sanchez-Mut JV, Aso E, Heyn H, Matsuda T, Bock C, Ferrer I, Esteller M. Promoter hypermethylation of the phosphatase DUSP22 mediates PKA-dependent TAU phosphorylation and CREB activation in Alzheimer’s disease. Hippocampus. 2014;24(4):363–8.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Sandoval J, Esteller M. Cancer epigenomics: beyond genomics. Curr Opin Genet Dev. 2012;22(1):50–5.

    CAS  PubMed  Google Scholar 

  • Sandoval J, Heyn H, Moran S, Serra-Musach J, Pujana MA, Bibikova M, Esteller M. Validation of a DNA methylation microarray for 450,000 CpG sites in the human genome. Epigenetics. 2011;6(6):692–702.

    CAS  PubMed  Google Scholar 

  • Sandoval J, Peiró-Chova L, Pallardó FV, García-Giménez JL. Epigenetic biomarkers in laboratory diagnostics: emerging approaches and opportunities. Expert Rev Mol Diagn. 2013a;13(5):457–71.

    CAS  PubMed  Google Scholar 

  • Sandoval J, Mendez-Gonzalez J, Nadal E, Chen G, Carmona FJ, Sayols S, Moran S, Heyn H, Vizoso M, Gomez A, Sanchez-Cespedes M, Assenov Y, Müller F, Bock C, Taron M, Mora J, Muscarella LA, Liloglou T, Davies M, Pollan M, Pajares MJ, Torre W, Montuenga LM, Brambilla E, Field JK, Roz L, Lo Iacono M, Scagliotti GV, Rosell R, Beer DG, Esteller M. A prognostic DNA methylation signature for stage I non-small cell lung cancer. J Clin Oncol. 2013b;31(32):4140–7.

    PubMed  Google Scholar 

  • Sanfiorenzo C, Ilie MI, Belaid A, Barlési F, Mouroux J, Marquette CH, Brest P, Hofman P. Two panels of plasma microRNAs as non-invasive biomarkers for prediction of recurrence in resectable NSCLC. PLoS One. 2013;8(1):e54596.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Schepeler T, Reinert JT, Ostenfeld MS, Christensen LL, Silahtaroglu AN, Dyrskjøt L, Wiuf C, Sørensen FJ, Kruhøffer M, Laurberg S, Kauppinen S, Ørntoft TF, Andersen CL. Diagnostic and prognostic microRNAs in stage II colon cancer. Cancer Res. 2008;68(15):6416–24.

    CAS  PubMed  Google Scholar 

  • Schweiger MR, Hussong M, Röhr C, Lehrach H. Genomics and epigenomics of colorectal cancer. Wiley Interdiscip Rev Syst Biol Med. 2013;5(2):205–19.

    CAS  PubMed  Google Scholar 

  • Selkoe DJ. Preventing Alzheimer’s disease. Science. 2012;337(6101):1488–92.

    CAS  PubMed  Google Scholar 

  • Sharma S, Kelly TK, Jones PA. Epigenetics in cancer. Carcinogenesis. 2010;31(1):27–36.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Shen L, Kondo Y, Ahmed S, Boumber Y, Konishi K, Guo Y, Chen X, Vilaythong JN, Issa JP. Drug sensitivity prediction by CpG island methylation profile in the NCI-60 cancer cell line panel. Cancer Res. 2007;67(23):11335–43.

    CAS  PubMed  Google Scholar 

  • Sherrington R, Rogaev EI, Liang Y, Rogaeva EA, Levesque G, Ikeda M, Chi H, Lin C, Li G, Holman K, Tsuda T, Mar L, Foncin JF, Bruni AC, Montesi MP, Sorbi S, Rainero I, Pinessi L, Nee L, Chumakov I, Pollen D, Brookes A, Sanseau P, Polinsky RJ, Wasco W, Da Silva HA, Haines JL, Perkicak-Vance MA, Tanzi RE, Roses AD, Fraser PE, Rommens JM, St George-Hyslop PH. Cloning of a gene bearing missense mutations in early-onset familial Alzheimer’s disease. Nature. 1995;375(6534):754–60.

    CAS  PubMed  Google Scholar 

  • 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(6):2156–62.

    CAS  PubMed  Google Scholar 

  • Shoemaker RH. The NCI60 human tumour cell line anticancer drug screen. Nat Rev Cancer. 2006;6(10):813–23.

    CAS  PubMed  Google Scholar 

  • Son JW, Jeong KJ, Jean WS, Park SY, Jheon S, Cho HM, Park CG, Lee HY, Kang J. Genome-wide combination profiling of DNA copy number and methylation for deciphering biomarkers in non-small cell lung cancer patients. Cancer Lett. 2011;311(1):29–37.

    CAS  PubMed  Google Scholar 

  • Song JS, Kim YS, Kim DK, Park SI, Jang SJ. Global histone modification pattern associated with recurrence and disease-free survival in non-small cell lung cancer patients. Pathol Int. 2012;62(3):182–90.

    PubMed  Google Scholar 

  • Sozzi G, Boeri M, Rossi M, Verri C, Suatoni P, Bravi F, Roz L, Conte D, Grassi M, Sverzellati N, Marchiano A, Negri E, La Vecchia C, Pastorino U. Clinical utility of a plasma-based miRNA signature classifier within computed tomography lung cancer screening: a correlative MILD trial study. J Clin Oncol. 2014;32(8):768–73.

    PubMed  Google Scholar 

  • Stefansson OA, Villanueva A, Vidal A, Martí L, Esteller M. BRCA1 epigenetic inactivation predicts sensitivity to platinum-based chemotherapy in breast and ovarian cancer. Epigenetics. 2012;7(11):1225–9.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Stratton MR, Campbell PJ, Futreal PA. The cancer genome. Nature. 2009;458(7239):719–24.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Szyf M. Epigenetics, DNA methylation, and chromatin modifying drugs. Annu Rev Pharmacol Toxicol. 2009;49:243–63.

    CAS  PubMed  Google Scholar 

  • Tang X, Khuri FR, Lee JJ, Kemp BL, Liu D, Hong WK, Mao L. Hypermethylation of the death-associated protein (DAP) kinase promoter and aggressiveness in stage I non-small cell lung cancer. J Natl Cancer Inst. 2000;92(18):1511–6.

    CAS  PubMed  Google Scholar 

  • Tang D, Liu J, Wang DR, Yu HF, Li YK, Zhang JQ. Diagnostic and prognostic value of the methylation status of secreted frizzled-related protein 2 in colorectal cancer. Clin Invest Med. 2011;34(2):E88–95.

    PubMed  Google Scholar 

  • Tanzi RE. The genetics of Alzheimer’s disease. Cold Spring Harb Perspect Med. 2012;2(10). pii: a006296.

    Google Scholar 

  • Timp W, Levchenko A, Feinberg AP. A new link between epigenetic progenitor lesions in cancer and the dynamics of signal transduction. Cell Cycle. 2009;8(3):383–90.

    CAS  PubMed  Google Scholar 

  • Tóth K, Sipos F, Kalmár A, Patai AV, Wichmann B, Stoehr R, Golcher H, Schellerer V, Tulassay Z, Molnár B. Detection of methylated SEPT9 in plasma is a reliable screening method for both left- and right-sided colon cancers. PLoS One. 2012;7(9):e46000.

    PubMed Central  PubMed  Google Scholar 

  • Toyooka S, Toyooka KO, Maruyama R, Virmani AK, Girard L, Miyajima K, Harada K, Ariyoshi Y, Takahashi T, Sugio K, Brambilla E, Gilcrease M, Minna JD, Gazdar AF. DNA methylation profiles of lung tumors. Mol Cancer Ther. 2001;1(1):61–7.

    CAS  PubMed  Google Scholar 

  • Turunen MP, Aavik E, Ylä-Herttuala S. Epigenetics and atherosclerosis. Biochim Biophys Acta. 2009;1790(9):886–91.

    CAS  PubMed  Google Scholar 

  • Usadel H, Brabender J, Danenberg KD, Jerónimo C, Harden S, Engles J, Danenberg PV, Yang S, Sidransky D. Quantitative adenomatous polyposis coli promoter methylation analysis in tumor tissue, serum, and plasma DNA of patients with lung cancer. Cancer Res. 2002;62(2):371–5.

    CAS  PubMed  Google Scholar 

  • Van Den Broeck A, Brambilla E, Moro-Sibilot D, Lantuejoul S, Brambilla C, Eymin B, Khochbin S, Gazzeri S. Loss of histone H4K20 trimethylation occurs in preneoplasia and influences prognosis of non-small cell lung cancer. Clin Cancer Res. 2008;14(22):7237–45.

    Google Scholar 

  • Van Neste L, Herman JG, Otto G, Bigley JW, Epstein JI, Van Criekinge W. The epigenetic promise for prostate cancer diagnosis. Prostate. 2012;72(11):1248–61.

    PubMed  Google Scholar 

  • Vasilatos SN, Broadwater G, Barry WT, Baker Jr JC, Lem S, Dietze EC, Bean GR, Bryson AD, Pilie PG, Goldenberg V, Skaar D, Paisie C, Torres-Hernandez A, Grant TL, Wilke LG, Ibarra-Drendall C, Ostrander JH, D’Amato NC, Zalles C, Jirtle R, Weaver VM, Seewaldt VL. CpG island tumor suppressor promoter methylation in non-BRCA-associated early mammary carcinogenesis. Cancer Epidemiol Biomarkers Prev. 2009;18(3):901–14.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Vaz C, Ahmad HM, Sharma P, Gupta R, Kumar L, Kulshreshtha R, Bhattacharya A. Analysis of microRNA transcriptome by deep sequencing of small RNA libraries of peripheral blood. BMC Genomics. 2010;11:288.

    PubMed Central  PubMed  Google Scholar 

  • Veeck J, Esteller M. Breast cancer epigenetics: from DNA methylation to microRNAs. J Mammary Gland Biol Neoplasia. 2010;15(1):5–17.

    PubMed Central  PubMed  Google Scholar 

  • Veeck J, Ropero S, Setien F, Gonzalez-Suarez E, Osorio A, Benitez J, Herman JG, Esteller M. BRCA1 CpG island hypermethylation predicts sensitivity to poly(adenosine diphosphate)-ribose polymerase inhibitors. J Clin Oncol. 2010;28(29):e563–4.

    PubMed  Google Scholar 

  • Vo QN, Kim WJ, Cvitanovic L, Boudreau DA, Ginzinger DG, Brown KD. The ATM gene is a target for epigenetic silencing in locally advanced breast cancer. Oncogene. 2004;23(58):9432–7.

    CAS  PubMed  Google Scholar 

  • Waddington C. The epigenotype. Endeavour. 1942;1:18–20.

    Google Scholar 

  • Walter K, Holcomb T, Januario T, Du P, Evangelista M, Kartha N, Iniguez L, Soriano R, Huw L, Stern H, Modrusan Z, Seshagiri S, Hampton GM, Amler LC, Bourgon R, Yauch RL, Shames DS. DNA methylation profiling defines clinically relevant biological subsets of non-small cell lung cancer. Clin Cancer Res. 2012;18(8):2360–73.

    CAS  PubMed  Google Scholar 

  • Wang Y, Yu Z, Wang T, Zhang J, Hong L, Chen L. Identification of epigenetic aberrant promoter methylation of RASSF1A in serum DNA and its clinicopathological significance in lung cancer. Lung Cancer. 2007;56(2):289–94.

    PubMed  Google Scholar 

  • Wang S, Xiang J, Li Z, Lu S, Hu J, Gao X, Yu L, Wang L, Wang J, Wu Y, Chen Z, Zhu H. A plasma microRNA panel for early detection of colorectal cancer. Int J Cancer. 2013;136(1):152–61.

    Google Scholar 

  • Warren JD, Xiong W, Bunker AM, Vaughn CP, Furtado LV, Roberts WL, Fang JC, Samowitz WS, Heichman KA. Septin 9 methylated DNA is a sensitive and specific blood test for colorectal cancer. BMC Med. 2011;9:133.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Widschwendter M, Jones PA. DNA methylation and breast carcinogenesis. Oncogene. 2002;21(35):5462–82.

    CAS  PubMed  Google Scholar 

  • World Health Organization. World health statistics report. 2011. http://www.who.int/whosis/whostat/2011/en/.

  • Wrangle J, Wang W, Koch A, Easwaran H, Mohammad HP, Vendetti F, Vancriekinge W, Demeyer T, Du Z, Parsana P, Rodgers K, Yen RW, Zahnow CA, Taube JM, Brahmer JR, Tykodi SS, Easton K, Carvajal RD, Jones PA, Laird PW, Weisenberger DJ, Tsai S, Juergens RA, Topalian SL, Rudin CM, Brock MV, Pardoll D, Baylin SB. Alterations of immune response of non-small cell lung cancer with azacytidine. Oncotarget. 2013;4(11):2067–79.

    PubMed Central  PubMed  Google Scholar 

  • Wrangle J, Machida EO, Danilova L, Hulbert A, Franco N, Zhang W, Glöckner SC, Tessema M, Van Neste L, Easwaran H, Schuebel KE, Licchesi J, Hooker CM, Ahuja N, Amano J, Belinsky SA, Baylin SB, Herman JG, Brock MV. Functional identification of cancer-specific methylation of CDO1, HOXA9, and TAC1 for the diagnosis of lung cancer. Clin Cancer Res. 2014;20(7):1856–64.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Wu WK, Law PT, Lee CW, Cho CH, Fan D, Wu K, Yu J, Sung JJ. MicroRNA in colorectal cancer: from benchtop to bedside. Carcinogenesis. 2011;32(3):247–53.

    CAS  PubMed  Google Scholar 

  • Xing X, Cai W, Shi H, Wang Y, Li M, Jiao J, Chen M. The prognostic value of CDKN2A hypermethylation in colorectal cancer: a meta-analysis. Br J Cancer. 2013a;108(12):2542–8.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Xing XB, Cai WB, Luo L, Liu LS, Shi HJ, Chen MH. The prognostic value of p16 hypermethylation in cancer: a meta-analysis. PLoS One. 2013b;8(6):e66587.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Xu X, Gammon MD, Zhang Y, Cho YH, Wetmur JG, Bradshaw PT, Garbowski G, Hibshoosh H, Teitelbaum SL, Neugut AI, Santella RM, Chen J. Gene promoter methylation is associated with increased mortality among women with breast cancer. Breast Cancer Res Treat. 2010;121(3):685–92.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Xu Z, Bolick SC, DeRoo LA, Weinberg CR, Sandler DP, Taylor JA. Epigenome-wide association study of breast cancer using prospectively collected sister study samples. J Natl Cancer Inst. 2013;105(10):694–700.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Yi JM, Dhir M, Van Neste L, Downing SR, Jeschke J, Glöckner SC, de Freitas Calmon M, Hooker CM, Funes JM, Boshoff C, Smits KM, van Engeland M, Weijenberg MP, Iacobuzio-Donahue CA, Herman JG, Schuebel KE, Baylin SB, Ahuja N. Genomic and epigenomic integration identifies a prognostic signature in colon cancer. Clin Cancer Res. 2011;17(6):1535–45.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Yu SL, Chen HY, Chang GC, Chen CY, Chen HW, Singh S, Cheng CL, Yu CJ, Lee YC, Chen HS, Su TJ, Chiang CC, Li HN, Hong QS, Su HY, Chen CC, Chen WJ, Liu CC, Chan WK, Chen WJ, Li KC, Chen JJ, Yang PC. MicroRNA signature predicts survival and relapse in lung cancer. Cancer Cell. 2008;13:48–57.

    CAS  PubMed  Google Scholar 

  • Zhang JX, Song W, Chen ZH, Wei JH, Liao YJ, Lei J, Hu M, Chen GZ, Liao B, Lu J, Zhao HW, Chen W, He YL, Wang HY, Xie D, Luo JH. Prognostic and predictive value of a microRNA signature in stage II colon cancer: a microRNA expression analysis. Lancet Oncol. 2013;14(13):1295–306.

    CAS  PubMed  Google Scholar 

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  1. Cancer Epigenetics and Biology Program (PEBC), Biomedical Research Institute of Bellvitge (IDIBELL), Hospital Duran i Reynals Av. Gran Via 199, 08907 – L’Hospitalet de Llobregat, Barcelona, Spain

    Jesus Mendez-Gonzalez

  2. Laboratory of Personalized Medicine, Genomic Unit, Instituto de Investigacion Sanitaria La Fe Torre A, Sótano. Avda. Fernando Abril Martorell, 106, 46026, Valencia, Spain

    Juan Sandoval PhD

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    Andrew E. Teschendorff

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Mendez-Gonzalez, J., Sandoval, J. (2015). Epigenomic Biomarkers for the Advance of Personalized Medicine. In: Teschendorff, A. (eds) Computational and Statistical Epigenomics. Translational Bioinformatics, vol 7. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-9927-0_9

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