M. Weber, I. Hellmann, M. B. Stadler, L. Ramos, S. Paabo et al., Distribution, silencing potential and evolutionary impact of promoter DNA methylation in the human genome, Nat Genet, vol.39, pp.457-66, 2007.

E. Li, T. H. Bestor, and R. Jaenisch, Targeted mutation of the DNA methyltransferase gene results in embryonic lethality, Cell, vol.69, pp.915-941, 1992.

E. Li, C. Beard, and R. Jaenisch, Role for DNA methylation in genomic imprinting, Nature, vol.366, pp.362-367, 1993.

E. Heard, P. Clerc, and P. Avner, X-chromosome inactivation in mammals, Annu Rev Genet, vol.31, pp.571-610, 1997.

S. A. Belinsky, W. A. Palmisano, F. D. Gilliland, L. A. Crooks, K. K. Divine et al., Aberrant promoter methylation in bronchial epithelium and sputum from current and former smokers, Cancer Res, vol.62, pp.2370-2377, 2002.

S. A. Belinsky, K. J. Nikula, W. A. Palmisano, R. Michels, G. Saccomanno et al., Aberrant methylation of p16(INK4a) is an early event in lung cancer and a potential biomarker for early diagnosis, Proc Natl Acad Sci, vol.95, pp.11891-11897, 1998.

M. Sato, Y. Mori, A. Sakurada, S. Fujimura, and A. Horii, The H-cadherin (CDH13) gene is inactivated in human lung cancer, Hum Genet, vol.103, pp.96-101, 1998.

H. Osada, Y. Tatematsu, Y. Yatabe, T. Nakagawa, H. Konishi et al., Frequent and histological typespecific inactivation of 14-3-3sigma in human lung cancers, Oncogene, vol.21, pp.2418-2442, 2002.

X. Tang, F. R. Khuri, J. J. Lee, B. L. Kemp, D. Liu et al., Hypermethylation of the death-associated protein (DAP) kinase promoter and aggressiveness in stage I non-small-cell lung cancer, J Natl Cancer Inst, vol.92, pp.1511-1517, 2000.

R. Dammann, C. Li, J. H. Yoon, P. L. Chin, S. Bates et al., Epigenetic inactivation of a RAS association domain family protein from the lung tumour suppressor locus 3p21.3, Nat Genet, vol.25, pp.315-324, 2000.

S. Hopkins-donaldson, A. Ziegler, S. Kurtz, C. Bigosch, D. Kandioler et al., Silencing of death receptor and caspase-8 expression in small cell lung carcinoma cell lines and tumors by DNA methylation, Cell Death Differ, vol.10, pp.356-64, 2003.

S. Zochbauer-muller, K. M. Fong, A. K. Virmani, J. Geradts, A. F. Gazdar et al., Aberrant promoter methylation of multiple genes in non-small cell lung cancers, Cancer Res, vol.61, pp.249-55, 2001.

R. M. Brena, C. Morrison, S. Liyanarachchi, D. Jarjoura, R. V. Davuluri et al., Aberrant DNA methylation of OLIG1, a novel prognostic factor in non-small cell lung cancer, Proc Natl Acad Sci, vol.4, pp.252-259, 2007.

S. Zhong, C. R. Fields, N. Su, Y. X. Pan, and K. D. Robertson, Pharmacologic inhibition of epigenetic modifications, coupled with gene expression profiling, reveals novel targets of aberrant DNA methylation and histone deacetylation in lung cancer, Oncogene, vol.26, pp.2621-2655, 2007.

D. S. Shames, L. Girard, B. Gao, M. Sato, C. M. Lewis et al., A genome-wide screen for promoter methylation in lung cancer identifies novel methylation markers for multiple malignancies, PLoS Med, vol.3, p.486, 2006.

R. K. Lin, H. S. Hsu, J. W. Chang, C. Y. Chen, J. T. Chen et al., Alteration of DNA methyltransferases contributes to 5'CpG methylation and poor prognosis in lung cancer, Lung Cancer, vol.55, pp.205-218, 2007.

H. Kim, Y. M. Kwon, J. S. Kim, J. Han, Y. M. Shim et al., Elevated mRNA levels of DNA methyltransferase-1 as an independent prognostic factor in primary nonsmall cell lung cancer, Cancer, vol.107, pp.1042-1051, 2006.

S. J. Lee, H. S. Jeon, J. S. Jang, S. H. Park, G. Y. Lee et al., DNMT3B polymorphisms and risk of primary lung cancer, Carcinogenesis, vol.26, pp.403-412, 2005.

C. Gridelli, A. Rossi, and P. Maione, The potential role of histone deacetylase inhibitors in the treatment of nonsmall-cell lung cancer, Crit Rev Oncol Hematol, vol.68, pp.29-36, 2008.

K. C. Cuneo, A. Fu, K. Osusky, J. Huamani, D. E. Hallahan et al., Histone deacetylase inhibitor NVP-LAQ824 sensitizes human nonsmall cell lung cancer to the cytotoxic effects of ionizing radiation, Anticancer Drugs, vol.18, pp.793-800, 2007.

N. Komatsu, N. Kawamata, S. Takeuchi, D. Yin, W. Chien et al., SAHA, a HDAC inhibitor, has profound anti-growth activity against non-small cell lung cancer cells, Oncol Rep, vol.15, pp.187-91, 2006.

M. Loprevite, M. Tiseo, F. Grossi, T. Scolaro, C. Semino et al., In vitro study of CI-994, a histone deacetylase inhibitor, in non-small cell lung cancer cell lines, Oncol Res, vol.15, pp.39-48, 2005.

S. Cang, Y. Ma, and D. Liu, New clinical developments in histone deacetylase inhibitors for epigenetic therapy of cancer, J Hematol Oncol, vol.2, p.22, 2009.

P. Sudarsanam and F. Winston, The Swi/Snf family nucleosome-remodeling complexes and transcriptional control, Trends Genet, vol.16, pp.345-51, 2000.

S. Glaros, G. M. Cirrincione, A. Palanca, D. Metzger, and D. Reisman, Targeted knockout of BRG1 potentiates lung cancer development, Cancer Res, vol.68, pp.3689-96, 2008.
URL : https://hal.archives-ouvertes.fr/inserm-00350882

P. P. Medina, J. Carretero, M. F. Fraga, M. Esteller, D. Sidransky et al., Genetic and epigenetic screening for gene alterations of the chromatinremodeling factor, SMARCA4/BRG1, in lung tumors, Genes Chromosomes Cancer, vol.41, pp.170-177, 2004.

L. Girard, S. Zochbauer-muller, A. K. Virmani, A. F. Gazdar, and J. D. Minna, Genome-wide allelotyping of lung cancer identifies new regions of allelic loss, differences between small cell lung cancer and non-small cell lung cancer, and loci clustering, Cancer Res, vol.60, pp.4894-906, 2000.

P. P. Medina and M. Sanchez-cespedes, Involvement of the chromatin-remodeling factor BRG1/SMARCA4 in human cancer, Epigenetics, vol.3, pp.64-72, 2008.

J. Fukuoka, T. Fujii, J. H. Shih, T. Dracheva, D. Meerzaman et al., Chromatin remodeling factors and BRM/BRG1 expression as prognostic indicators in non-small cell lung cancer, Clin Cancer Res, vol.10, pp.4314-4338, 2004.

D. N. Reisman, J. Sciarrotta, W. Wang, W. K. Funkhouser, and B. E. Weissman, Loss of BRG1/BRM in human lung cancer cell lines and primary lung cancers: correlation with poor prognosis, Cancer Res, vol.63, pp.560-566, 2003.

A. Esquela-kerscher and F. J. Slack, Oncomirs-microRNAs with a role in cancer, Nat Rev Cancer, vol.6, pp.259-69, 2006.

G. A. Calin and C. M. Croce, MicroRNA signatures in human cancers, Nat Rev Cancer, vol.6, pp.857-66, 2006.

S. Volinia, G. A. Calin, C. G. Liu, S. Ambs, A. Cimmino et al., A microRNA expression signature of human solid tumors defines cancer gene targets, Proc Natl Acad Sci, vol.103, pp.2257-61, 2006.

N. Yanaihara, N. Caplen, E. Bowman, M. Seike, K. Kumamoto et al., Unique microRNA molecular profiles in lung cancer diagnosis and prognosis, Cancer Cell, vol.9, pp.189-98, 2006.

J. Takamizawa, H. Konishi, K. Yanagisawa, S. Tomida, H. Osada et al., Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival, Cancer Res, vol.64, pp.3753-3759, 2004.

S. M. Johnson, H. Grosshans, J. Shingara, M. Byrom, R. Jarvis et al., RAS is regulated by the let-7 microRNA family, Cell, vol.120, pp.635-682, 2005.

C. D. Johnson, A. Esquela-kerscher, G. Stefani, M. Byrom, K. Kelnar et al., The let-7 microR-NA represses cell proliferation pathways in human cells, Cancer Res, vol.67, pp.7713-7735, 2007.

F. De-fraipont, D. Moro-sibilot, S. Michelland, E. Brambilla, C. Brambilla et al., Promoter methylation of genes in bronchial lavages: a marker for early diagnosis of primary and relapsing non-small cell lung cancer?, Lung Cancer, vol.50, pp.199-209, 2005.

M. V. Brock, C. M. Hooker, E. Ota-machida, Y. Han, M. Guo et al., DNA methylation markers and early recurrence in stage I lung cancer, N Engl J Med, vol.358, pp.1118-1146, 2008.

J. P. Issa, DNA methylation as a therapeutic target in cancer, Clin Cancer Res, vol.13, pp.1634-1641, 2007.

R. L. Momparler, N. Eliopoulos, and J. Ayoub, Evaluation of an inhibitor of DNA methylation, 5-aza-2'-deoxycytidine, for the treatment of lung cancer and the future role of gene therapy, Adv Exp Med Biol, vol.465, pp.433-479, 2000.

D. B. Seligson, S. Horvath, M. A. Mcbrian, V. Mah, H. Yu et al., Global levels of histone modifications predict prognosis in different cancers, Am J Pathol, vol.174, pp.1619-1647, 2009.

M. F. Fraga, E. Ballestar, A. Villar-garea, M. Boix-chornet, J. Espada et al., Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer, Nat Genet, vol.37, pp.391-400, 2005.

A. Van-den-broeck, E. Brambilla, D. Moro-sibilot, S. Lantuejoul, C. Brambilla et al., Loss of histone H4K20 trimethylation occurs in preneoplasia and influences prognosis of non-small cell lung cancer, Clin Cancer Res, vol.14, pp.7237-7282, 2008.
URL : https://hal.archives-ouvertes.fr/inserm-00372185

G. Schotta, R. Sengupta, S. Kubicek, S. Malin, M. Kauer et al., A chromatin-wide transition to H4K20 monomethylation impairs genome integrity and programmed DNA rearrangements in the mouse, Genes Dev, vol.22, pp.2048-61, 2008.

. Me, . Ll, F. Vidal, D. Gallardo, M. Diaz-fuertes et al., New p53 related genes in human tumors: significant downregulation in colon and lung carcinomas, Oncol Rep, vol.16, pp.603-611, 2006.

T. Kouzarides, Chromatin modifications and their function, Cell, vol.128, pp.693-705, 2007.

A. Vaquero, R. Sternglanz, and D. Reinberg, NAD + -dependent deacetylation of H4 lysine 16 by class III HDACs, Oncogene, vol.26, pp.5505-5525, 2007.

M. Kishimoto, T. Kohno, K. Okudela, A. Otsuka, H. Sasaki et al., Mutations and deletions of the CBP gene in human lung cancer, Clin Cancer Res, vol.11, pp.512-521, 2005.

H. Osada, Y. Tatematsu, H. Saito, Y. Yatabe, T. Mitsudomi et al., Reduced expression of class II histone deacetylase genes is associated with poor prognosis in lung cancer patients, Int J Cancer, vol.112, pp.26-32, 2004.

H. Sasaki, S. Moriyama, Y. Nakashima, Y. Kobayashi, M. Kiriyama et al., Histone deacetylase 1 mRNA expression in lung cancer, Lung Cancer, vol.46, pp.171-179, 2004.

A. Italiano, R. Attias, A. Aurias, G. Perot, F. Burel-vandenbos et al., Molecular cytogenetic characterization of a metastatic lung sarcomatoid carcinoma: 9p23 neocentromere and 9p23-p24 amplification including JAK2 and JMJD2C, Cancer Genet Cytogenet, vol.167, pp.122-152, 2006.

C. Suzuki, K. Takahashi, S. Hayama, N. Ishikawa, T. Kato et al., Identification of Myc-associated protein with JmjC domain as a novel therapeutic target oncogene for lung cancer, Mol Cancer Ther, vol.6, pp.542-51, 2007.

F. Barlesi, G. Giaccone, M. I. Gallegos-ruiz, A. Loundou, S. W. Span et al., Global histone modifications predict prognosis of resected non small-cell lung cancer, J Clin Oncol, vol.25, pp.4358-64, 2007.

D. B. Seligson, S. Horvath, T. Shi, H. Yu, S. Tze et al., Global histone modification patterns predict risk of prostate cancer recurrence, Nature, vol.435, pp.1262-1268, 2005.

H. Shen, L. Wang, M. R. Spitz, W. K. Hong, L. Mao et al., A novel polymorphism in human cytosine DNA-methyltransferase-3B promoter is associated with an increased risk of lung cancer, Cancer Res, vol.62, pp.4992-4997, 2002.

A. Anisowicz, H. Huang, K. I. Braunschweiger, Z. Liu, H. Giese et al., A high-throughput and sensitive method to measure global DNA methylation: application in lung cancer, BMC Cancer, vol.8, p.222, 2008.

K. Woodson, J. Mason, S. W. Choi, T. Hartman, J. Tangrea et al., Hypomethylation of p53 in peripheral blood DNA is associated with the development of lung cancer, Cancer Epidemiol Biomarkers Prev, vol.10, pp.69-74, 2001.

G. P. Pfeifer and T. A. Rauch, DNA methylation patterns in lung carcinomas, Semin Cancer Biol, vol.19, pp.181-188, 2009.

K. Chalitchagorn, S. Shuangshoti, N. Hourpai, N. Kongruttanachok, P. Tangkijvanich et al., Distinctive pattern of LINE-1 methylation level in normal tissues and the association with carcinogenesis, Oncogene, vol.23, pp.8841-8847, 2004.

A. P. Feinberg, R. Ohlsson, and S. Henikoff, The epigenetic progenitor origin of human cancer, Nat Rev Genet, vol.7, pp.21-33, 2006.

S. Tornaletti and G. P. Pfeifer, Complete and tissue-independent methylation of CpG sites in the p53 gene: implications for mutations in human cancers, Oncogene, vol.10, pp.1493-1502, 1995.

P. A. Jones, W. M. Rideout, J. C. Shen, C. H. Spruck, and Y. C. Tsai, Methylation, mutation and cancer, Bioessays, vol.14, pp.33-39, 1992.

L. E. Smith, M. F. Denissenko, W. P. Bennett, H. Li, S. Amin et al., Targeting of lung cancer mutational hotspots by polycyclic aromatic hydrocarbons, J Natl Cancer Inst, vol.92, pp.803-814, 2000.

J. H. Yoon, L. E. Smith, Z. Feng, M. Tang, C. S. Lee et al., Methylated CpG dinucleotides are the preferential targets for G-to-T transversion mutations induced by benzo[a]pyrene diol epoxide in mammalian cells: similarities with the p53 mutation spectrum in smokingassociated lung cancers, Cancer Res, vol.61, pp.7110-7117, 2001.

M. F. Denissenko, J. X. Chen, M. S. Tang, and G. P. Pfeifer, Cytosine methylation determines hot spots of DNA damage in the human p53 gene, Proc Natl Acad Sci, vol.94, pp.3893-3901, 1997.

A. N. Magewu and P. A. Jones, Ubiquitous and tenacious methylation of the CpG site in codon 248 of the p53 gene may explain its frequent appearance as a mutational hot spot in human cancer, Mol Cell Biol, vol.14, pp.4225-4257, 1994.

F. V. Jacinto and M. Esteller, Mutator pathways unleashed by epigenetic silencing in human cancer, Mutagenesis, vol.22, pp.247-53, 2007.

M. Esteller, S. R. Hamilton, P. C. Burger, S. B. Baylin, and J. G. Herman, Inactivation of the DNA repair gene O 6 -methylguanine-DNA methyltransferase by promoter hypermethylation is a common event in primary human neoplasia, Cancer Res, vol.59, pp.793-800, 1999.

M. Esteller, R. A. Risques, M. Toyota, G. Capella, V. Moreno et al., Promoter hypermethylation of the DNA repair gene O(6)-methylguanine-DNA methyltransferase is associated with the presence of G:C to A:T transition mutations in p53 in human colorectal tumorigenesis, Cancer Res, vol.61, pp.4689-92, 2001.

J. Y. Wu, J. Wang, J. C. Lai, Y. W. Cheng, K. T. Yeh et al., Association of O 6 -methylguanine-DNA methyltransferase (MGMT) promoter methylation with p53 mutation occurrence in non-small cell lung cancer with different histology, gender and smoking status, Ann Surg Oncol, vol.15, pp.3272-3279, 2008.

S. Zochbauer-muller, S. Lam, S. Toyooka, A. K. Virmani, K. O. Toyooka et al., Aberrant methylation of multiple genes in the upper aerodigestive tract epithelium of heavy smokers, Int J Cancer, vol.107, pp.612-618, 2003.

W. A. Palmisano, K. K. Divine, G. Saccomanno, F. D. Gilliland, S. B. Baylin et al., Predicting lung cancer by detecting aberrant promoter methylation in sputum, Cancer Res, vol.60, pp.5954-5962, 2000.

G. Rabinowits, C. Gercel-taylor, J. M. Day, D. D. Taylor, and G. H. Kloecker, Exosomal microRNA: a diagnostic marker for lung cancer, Clin Lung Cancer, vol.10, pp.42-48, 2009.

A. Markou, E. G. Tsaroucha, L. Kaklamanis, M. Fotinou, V. Georgoulias et al., Prognostic value of mature microRNA-21 and microRNA-205 overexpression in non-small cell lung cancer by quantitative realtime RT-PCR, Clin Chem, vol.54, pp.1696-704, 2008.

S. L. Yu, H. Y. Chen, G. C. Chang, C. Y. Chen, H. W. Chen et al., MicroRNA signature predicts survival and relapse in lung cancer, Cancer Cell, vol.13, pp.48-57, 2008.

J. B. Weidhaas, I. Babar, S. M. Nallur, P. Trang, S. Roush et al., MicroRNAs as potential agents to alter resistance to cytotoxic anticancer therapy, Cancer Res, vol.67, pp.11111-11117, 2007.

M. Garofalo, C. Quintavalle, D. Leva, G. Zanca, C. Romano et al., MicroRNA signatures of TRAIL resistance in human non-small cell lung cancer, Oncogene, vol.27, pp.3845-55, 2008.

J. Krutzfeldt, N. Rajewsky, R. Braich, K. G. Rajeev, T. Tuschl et al., Silencing of microRNAs in vivo with 'antagomirs', Nature, vol.438, pp.685-694, 2005.

A. Izzotti, G. A. Calin, V. E. Steele, C. M. Croce, D. Flora et al., Relationships of microRNA expression in mouse lung with age and exposure to cigarette smoke and light, FASEB J, 2009.

L. He, X. He, L. P. Lim, E. De-stanchina, X. Z. Liang et al., A microRNA component of the p53 tumour suppressor network, Nature, vol.447, pp.1130-1134, 2007.

A. Lujambio, S. Ropero, E. Ballestar, M. F. Fraga, C. Cerrato et al., Genetic unmasking of an epigenetically silenced microRNA in human cancer cells, Cancer Res, vol.67, pp.1424-1433, 2007.

Y. Karube, H. Tanaka, H. Osada, S. Tomida, Y. Tatematsu et al., Reduced expression of Dicer associated with poor prognosis in lung cancer patients, Cancer Sci, vol.96, pp.111-116, 2005.

Y. Liang, An expression meta-analysis of predicted microRNA targets identifies a diagnostic signature for lung cancer, BMC Med Genomics, vol.1, p.61, 2008.

D. Lebanony, H. Benjamin, S. Gilad, M. Ezagouri, A. Dov et al., Diagnostic assay based on hsa-miR-205 expression distinguishes squamous from nonsquamous non-small-cell lung carcinoma, J Clin Oncol, vol.27, pp.2030-2037, 2009.

Y. Xie, N. W. Todd, Z. Liu, M. Zhan, H. Fang et al., Altered miRNA expression in sputum for diagnosis of non-small cell lung cancer, Lung Cancer, vol.67, pp.170-176, 2010.

X. Chen, Y. Ba, L. Ma, X. Cai, Y. Yin et al., Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases, Cell Res, vol.18, pp.997-1006, 2008.

G. J. Weiss, L. T. Bemis, E. Nakajima, M. Sugita, D. K. Birks et al., EGFR regulation by microRNA in lung cancer: correlation with clinical response and survival to gefitinib and EGFR expression in cell lines, Ann Oncol, vol.19, pp.1053-1062, 2008.

Y. Hayashita, H. Osada, Y. Tatematsu, H. Yamada, K. Yanagisawa et al., A polycistronic microR-NA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation, Cancer Res, vol.65, pp.9628-9660, 2005.

H. Matsubara, T. Takeuchi, E. Nishikawa, K. Yanagisawa, Y. Hayashita et al., Apoptosis induction by antisense oligonucleotides against miR-17-5p and miR-20a in lung cancers overexpressing miR-17-92, Oncogene, vol.26, pp.6099-105, 2007.

Y. Lu, J. M. Thomson, H. Y. Wong, S. M. Hammond, and B. L. Hogan, Transgenic overexpression of the microRNA miR-17-92 cluster promotes proliferation and inhibits differentiation of lung epithelial progenitor cells, Dev Biol, vol.310, pp.442-53, 2007.

K. A. O'donnell, E. A. Wentzel, K. I. Zeller, C. V. Dang, and J. T. Mendell, c-Myc-regulated microRNAs modulate E2F1 expression, Nature, vol.435, pp.839-882, 2005.

B. Eymin, S. Gazzeri, C. Brambilla, and E. Brambilla, Distinct pattern of E2F1 expression in human lung tumours: E2F1 is upregulated in small cell lung carcinoma, Oncogene, vol.20, pp.1678-87, 2001.

B. P. Lewis, I. H. Shih, M. W. Jones-rhoades, D. P. Bartel, and C. B. Burge, Prediction of mammalian microRNA targets, Cell, vol.115, pp.787-98, 2003.

M. S. Kumar, J. Lu, K. L. Mercer, T. R. Golub, and T. Jacks, Impaired microRNA processing enhances cellular transformation and tumorigenesis, Nat Genet, vol.39, pp.673-680, 2007.