S. B. Baylin and P. A. Jones, A decade of exploring the cancer epigenome -biological and translational implications, Nat Rev Cancer, vol.11, issue.10, pp.726-734, 2011.

C. C. Simons, L. A. Hughes, K. M. Smits, C. A. Khalid-de-bakker, A. P. De-bruine et al., A novel classification of colorectal tumors based on microsatellite instability, the CpG island methylator phenotype and chromosomal instability: implications for prognosis, Ann Oncol, vol.24, issue.8, pp.2048-2056, 2013.

M. Toyota, M. Ohe-toyota, A. N. Issa, and J. P. , Distinct genetic profiles in colorectal tumors with or without the CpG island methylator phenotype, Proc Natl Acad Sci, vol.97, issue.2, pp.710-715, 2000.

L. Barault, C. Charon-barra, V. Jooste, M. F. De-la-vega, L. Martin et al., Hypermethylator www.impactjournals.com/oncotarget phenotype in sporadic colon cancer: study on a populationbased series of 582 cases, Cancer Res, vol.68, issue.20, pp.8541-8546, 2008.

R. L. Siegel and K. D. Miller, Cancer statistics, CA Cancer J Clin, vol.65, issue.1, pp.5-29, 2015.

S. Ogino, J. A. Meyerhardt, T. Kawasaki, J. W. Clark, D. P. Ryan et al., CpG island methylation, response to combination chemotherapy, and patient survival in advanced microsatellite stable colorectal carcinoma, Virchows Arch, vol.450, issue.5, pp.529-537, 2007.

L. Shen, P. J. Catalano, A. B. Benson, P. Dwyer, H. Sr et al., Association between DNA methylation and shortened survival in patients with advanced colorectal cancer treated with 5-fluorouracil based chemotherapy, Clin Cancer Res, vol.13, issue.20, pp.6093-6098, 2007.

R. L. Ward, K. Cheong, S. L. Ku, A. Meagher, T. O'connor et al., Adverse prognostic effect of methylation in colorectal cancer is reversed by microsatellite instability, J Clin Oncol, vol.21, issue.20, pp.3729-3736, 2003.

S. H. Wei, C. M. Chen, G. Strathdee, J. Harnsomburana, C. R. Shyu et al., Methylation microarray analysis of late-stage ovarian carcinomas distinguishes progressionfree survival in patients and identifies candidate epigenetic markers, Clin Cancer Res, vol.8, issue.7, pp.2246-2252, 2002.

R. M. Glasspool, J. M. Teodoridis, and R. Brown, Epigenetics as a mechanism driving polygenic clinical drug resistance, Br J Cancer, vol.94, issue.8, pp.1087-1092, 2006.

T. Kanda, M. Tada, F. Imazeki, O. Yokosuka, K. Nagao et al., 5-aza-2'-deoxycytidine sensitizes hepatoma and pancreatic cancer cell lines, Oncol Rep, vol.14, issue.4, pp.975-979, 2005.

S. Cheetham, M. J. Tang, F. Mesak, H. Kennecke, O. D. et al., SPARC promoter hypermethylation in colorectal cancers can be reversed by 5-Aza-2'deoxycytidine to increase SPARC expression and improve therapy response, Br J Cancer, vol.98, issue.11, pp.1810-1819, 2008.

Y. Watanabe, H. Ueda, T. Etoh, E. Koike, N. Fujinami et al., A change in promoter methylation of hMLH1 is a cause of acquired resistance to platinum-based chemotherapy in epithelial ovarian cancer, Anticancer Res, vol.27, issue.3B, pp.1449-1452, 2007.

J. A. Plumb, G. Strathdee, J. Sludden, K. Sb, and R. Brown, Reversal of drug resistance in human tumor xenografts by 2'-deoxy-5-azacytidine-induced demethylation of the hMLH1 gene promoter, Cancer Res, vol.60, issue.21, pp.6039-6044, 2000.

T. Qin, J. Si, N. J. Raynal, X. Wang, V. Gharibyan et al., Epigenetic synergy between decitabine and platinum derivatives, Clin Epigenetics, vol.7, issue.1, p.97, 2015.

M. Candelaria, D. Gallardo-rincon, C. Arce, L. Cetina, J. L. Aguilar-ponce et al., A phase II study of epigenetic therapy with hydralazine and magnesium valproate to overcome chemotherapy resistance in refractory solid tumors, Ann Oncol, vol.18, issue.9, pp.1529-1538, 2007.

R. C. Bast, R. B. Iyer, W. Hu, J. Kavanagh, R. L. Coleman et al., A phase IIa study of sequential regimen using azacitidine to reverse platinum resistance to carboplatin in patietns with platinum resistant or refracoty epithelial ovarian cancer, J Clin Oncol (Meeting Abstracts), vol.26, pp.15-3500, 2008.

Y. M. Liao, H. Mirshahidi, . Zk, S. Mirshahidi, S. Williamson et al., Phase I study of azacitidine and cisplatin in patients with advanced head and neck or non-small cell lung cancer, Proceedings of the 103rd Annual Meeting of the, 2012.

, Abstract nr 2663 doi, vol.72, pp.1538-7445, 2012.

R. A. Juergens, J. Wrangle, F. P. Vendetti, S. C. Murphy, M. Zhao et al., Combination epigenetic therapy has efficacy in patients with refractory advanced non-small cell lung cancer, Cancer Discov, vol.1, issue.7, pp.598-607, 2011.

M. Li, W. D. Chen, N. Papadopoulos, S. N. Goodman, N. C. Bjerregaard et al., Sensitive digital quantification of DNA methylation in clinical samples, Nat Biotechnol, vol.27, issue.9, pp.858-863, 2009.

H. Zou, J. J. Harrington, A. M. Shire, R. L. Rego, L. Wang et al., Highly methylated genes in colorectal neoplasia: implications for screening, Cancer Epidemiol Biomarkers Prev, vol.16, issue.12, pp.2686-2696, 2007.

W. D. Chen, Z. J. Han, J. Skoletsky, J. Olson, J. Sah et al., Detection in fecal DNA of colon cancer-specific methylation of the nonexpressed vimentin gene, J Natl Cancer Inst, vol.97, issue.15, pp.1124-1132, 2005.

D. J. Stewart, J. P. Issa, R. Kurzrock, M. I. Nunez, J. Jelinek et al., Decitabine effect on tumor global DNA methylation and other parameters in a phase I trial in refractory solid tumors and lymphomas, Clin Cancer Res, vol.15, issue.11, pp.3881-3888, 2009.

K. Appleton, H. J. Mackay, J. I. Plumb, J. A. Mccormick, C. Strathdee et al., Phase I and pharmacodynamic trial of the DNA methyltransferase inhibitor decitabine and carboplatin www.impactjournals.com/oncotarget in solid tumors, J Clin Oncol, vol.25, issue.29, pp.4603-4609, 2007.

A. M. Tsimberidou, R. Said, K. Culotta, I. Wistuba, J. Jelinek et al.,

, Phase I study of azacitidine and oxaliplatin in patients with advanced cancers that have relapsed or are refractory to any platinum therapy, Clin Epigenetics, vol.7, issue.1, p.29, 2015.

A. Aparicio, C. A. Eads, L. A. Leong, P. W. Laird, E. M. Newman et al., Phase I trial of continuous infusion 5-aza-2'-deoxycytidine, Cancer chemotherapy and pharmacology, vol.51, issue.3, pp.231-239, 2003.

T. Reid, B. Oronsky, J. Scicinski, C. L. Scribner, S. J. Knox et al., Safety and activity of RRx-001 in patients with advanced cancer: a first-in-human, open-label, doseescalation phase 1 study, Lancet Oncol, vol.16, issue.9, pp.1133-1142, 2015.

H. Kantarjian, Y. Oki, G. Garcia-manero, X. Huang, S. O'brien et al., Results of a randomized study of 3 schedules of lowdose decitabine in higher-risk myelodysplastic syndrome and chronic myelomonocytic leukemia, Blood, vol.109, issue.1, pp.52-57, 2007.

P. S. Haas, P. Wijermans, G. Verhoef, and M. Lubbert, Treatment of myelodysplastic syndrome with a DNA methyltransferase inhibitor: lack of evidence for induction of chromosomal instability, Leuk Res, vol.30, issue.3, pp.338-342, 2006.

P. W. Hollenbach, A. N. Nguyen, H. Brady, M. Williams, Y. Ning et al., A comparison of azacitidine and decitabine activities in acute myeloid leukemia cell lines, PloS one, vol.5, issue.2, p.9001, 2010.

D. Ahmed, P. W. Eide, I. A. Eilertsen, S. A. Danielsen, M. Eknaes et al., Epigenetic and genetic features of 24 colon cancer cell lines, Oncogenesis, vol.2, p.71, 2013.

G. E. Tusnady, I. Simon, A. Varadi, and T. Aranyi, BiSearch: primer-design and search tool for PCR on bisulfite-treated genomes, Nucleic acids research, vol.33, issue.1, p.9, 2005.

T. Aranyi, A. Varadi, S. I. Tusnady, and G. E. , The BiSearch web server, BMC bioinformatics, vol.7, p.431, 2006.

P. Du, X. Zhang, C. C. Huang, N. Jafari, W. A. Kibbe et al., Comparison of Beta-value and M-value methods for quantifying methylation levels by microarray analysis, BMC Bioinformatics, vol.11, p.587, 2010.

, Comprehensive molecular characterization of human colon and rectal cancer, Nature, vol.487, issue.7407, pp.330-337, 2012.

A. S. Yang, M. R. Estecio, K. Doshi, Y. Kondo, E. H. Tajara et al., A simple method for estimating global DNA methylation using bisulfite PCR of repetitive DNA elements, Nucleic Acids Res, vol.32, issue.3, p.38, 2004.

J. P. Issa, G. Garcia-manero, F. J. Giles, R. Mannari, D. Thomas et al., Phase 1 study of low-dose prolonged exposure schedules of the hypomethylating agent 5-aza-2'-deoxycytidine (decitabine) in hematopoietic malignancies, Blood, vol.103, issue.5, pp.1635-1640, 2004.