F. Barlesi, J. Mazieres, J. Merlio, D. Debieuvre, J. Mosser et al., Routine molecular profiling of patients with advanced nonsmall-cell lung cancer: results of a 1-year nationwide programme of the French Cooperative Thoracic Intergroup (IFCT) The Lancet, pp.1415-1426, 2016.

M. Beau-faller, H. Blons, C. Domerg, D. Gajda, N. Richard et al., A Multicenter Blinded Study Evaluating EGFR and KRAS Mutation Testing Methods in the Clinical Non???Small Cell Lung Cancer Setting???IFCT/ERMETIC2 Project Part 1, The Journal of Molecular Diagnostics, vol.16, issue.1, pp.45-55, 2014.
DOI : 10.1016/j.jmoldx.2013.07.009

URL : https://hal.archives-ouvertes.fr/hal-01064291

C. Bosc, G. R. Ferretti, J. Cadranel, C. Audigier-valette, B. Besse et al., Rebiopsy during disease progression in patients treated by TKI for oncogene-addicted NSCLC, Targeted Oncology, vol.359, issue.4, pp.247-253, 2015.
DOI : 10.1007/s11523-014-0332-y

J. Cadranel, A. Ruppert, M. Beau-faller, and M. Wislez, Therapeutic strategy for advanced EGFR mutant non-small-cell lung carcinoma, Critical Reviews in Oncology/Hematology, vol.88, issue.3, pp.477-493, 2013.
DOI : 10.1016/j.critrevonc.2013.06.009

X. Cai, F. Janku, Q. Zhan, F. , and J. , Accessing Genetic Information with Liquid Biopsies, Trends in Genetics, vol.31, issue.10, pp.564-575, 2015.
DOI : 10.1016/j.tig.2015.06.001

L. E. Coate, T. John, M. Tsao, and F. A. Shepherd, Molecular predictive and prognostic markers in non-small-cell lung cancer, The Lancet Oncology, vol.10, issue.10, pp.1001-1010, 2009.
DOI : 10.1016/S1470-2045(09)70155-X

L. A. Diaz and A. Bardelli, Liquid Biopsies: Genotyping Circulating Tumor DNA, Journal of Clinical Oncology, vol.32, issue.6, pp.579-586, 2014.
DOI : 10.1200/JCO.2012.45.2011

URL : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4820760

A. Didelot, D. Le-corre, A. Luscan, A. Cazes, K. Pallier et al., Competitive allele specific TaqMan PCR for KRAS, BRAF and EGFR mutation detection in clinical formalin fixed paraffin embedded samples, Experimental and Molecular Pathology, vol.92, issue.3, pp.275-280, 2012.
DOI : 10.1016/j.yexmp.2012.03.001

A. Didelot, S. K. Kotsopoulos, A. Lupo, D. Pekin, X. Li et al., Multiplex Picoliter-Droplet Digital PCR for Quantitative Assessment of DNA Integrity in Clinical Samples, Clinical Chemistry, vol.59, issue.5, pp.815-823, 2013.
DOI : 10.1373/clinchem.2012.193409

F. Diehl, M. Li, D. Dressman, Y. He, D. Shen et al., Detection and quantification of mutations in the plasma of patients with colorectal tumors, Proceedings of the National Academy of Sciences, vol.315, issue.1-2, pp.16368-16373, 2005.
DOI : 10.1016/S0009-8981(01)00712-4

F. Diehl, K. Schmidt, M. A. Choti, K. Romans, S. Goodman et al., Circulating mutant DNA to assess tumor dynamics, Nature Medicine, vol.3, issue.9, pp.985-990, 2008.
DOI : 10.1038/nm.1789

URL : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2820391

L. Ding, G. Getz, D. A. Wheeler, E. R. Mardis, M. D. Mclellan et al., Somatic mutations affect key pathways in lung adenocarcinoma, Nature, vol.32, issue.7216, pp.1069-1075, 2008.
DOI : 10.1038/nature07423

J. Douillard, G. Ostoros, M. Cobo, T. Ciuleanu, R. Cole et al., Gefitinib Treatment in EGFR Mutated Caucasian NSCLC: Circulating-Free Tumor DNA as a Surrogate for Determination of EGFR Status, Journal of Thoracic Oncology, vol.9, issue.9, pp.1345-1353, 2014.
DOI : 10.1097/JTO.0000000000000263

J. Ferlay, I. Soerjomataram, R. Dikshit, S. Eser, C. Mathers et al., Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012, International Journal of Cancer, vol.13, issue.5, pp.359-386, 2015.
DOI : 10.1002/ijc.29210

A. F. Gazdar, Epidermal growth factor receptor inhibition in lung cancer: the evolving role of individualized therapy, Cancer and Metastasis Reviews, vol.27, issue.15, pp.37-48, 2010.
DOI : 10.1007/s10555-010-9201-z

A. F. Gazdar and M. J. Thun, Lung Cancer, Smoke Exposure, and Sex, Journal of Clinical Oncology, vol.25, issue.5, pp.469-471, 2007.
DOI : 10.1200/JCO.2006.09.4623

S. Guérin and C. Hill, L'épidémiologie des cancers en France en 2010 : comparaison avec les États-Unis, Bull. Cancer (Paris), vol.97, pp.47-54, 2010.

D. Hanahan and R. A. Weinberg, The Hallmarks of Cancer, Cell, vol.100, issue.1, pp.57-70, 2000.
DOI : 10.1016/S0092-8674(00)81683-9

D. Hanahan and R. A. Weinberg, Hallmarks of Cancer: The Next Generation, Cell, vol.144, issue.5, pp.646-674, 2011.
DOI : 10.1016/j.cell.2011.02.013

S. Holdenrieder and P. Stieber, Apoptotic markers in cancer, Clinical Biochemistry, vol.37, issue.7, pp.605-617, 2004.
DOI : 10.1016/j.clinbiochem.2004.05.003

B. E. Johnson, J. , and P. A. , Epidermal growth factor receptor mutations in patients with non?small cell lung cancer, Cancer Res, vol.65, pp.7525-7529, 2005.

K. M. Kerr, L. Bubendorf, M. J. Edelman, A. Marchetti, T. Mok et al., Second ESMO consensus conference on lung cancer: pathology and molecular biomarkers for non-small-cell lung cancer, Annals of Oncology, vol.25, issue.9, pp.1681-1690, 2014.
DOI : 10.1093/annonc/mdu145

T. Lecomte, A. Berger, F. Zinzindohoué, S. Micard, B. Landi et al., Detection of free-circulating tumor-associated DNA in plasma of colorectal cancer patients and its association with prognosis, International Journal of Cancer, vol.11, issue.5, pp.542-548, 2002.
DOI : 10.1002/ijc.10526

T. Lecomte, N. Ceze, É. Dorval, and P. Laurent-puig, Circulating free tumor DNA and colorectal cancer, Gastroent??rologie Clinique et Biologique, vol.34, issue.12, pp.662-681, 2010.
DOI : 10.1016/j.gcb.2009.04.015

URL : https://hal.archives-ouvertes.fr/hal-00618040

Y. J. Lee, K. Yoon, J. Han, H. T. Kim, T. Yun et al., Circulating Cell-Free DNA in Plasma of Never Smokers with Advanced Lung Adenocarcinoma Receiving Gefitinib or Standard Chemotherapy as First-Line Therapy, Clinical Cancer Research, vol.17, issue.15, pp.5179-5187, 2011.
DOI : 10.1158/1078-0432.CCR-11-0400

T. Li, H. Kung, P. C. Mack, and D. R. Gandara, Genotyping and Genomic Profiling of Non???Small-Cell Lung Cancer: Implications for Current and Future Therapies, Journal of Clinical Oncology, vol.31, issue.8, pp.1039-1049, 2013.
DOI : 10.1200/JCO.2012.45.3753

H. Linardou, I. J. Dahabreh, D. Kanaloupiti, F. Siannis, D. Bafaloukos et al., Assessment of somatic k-RAS mutations as a mechanism associated with resistance to EGFR-targeted agents: a systematic review and meta-analysis of studies in advanced non-small-cell lung cancer and metastatic colorectal cancer, The Lancet Oncology, vol.9, issue.10, pp.962-972, 2008.
DOI : 10.1016/S1470-2045(08)70206-7

X. Liu, X. J. Lin, C. P. Wang, K. K. Yan, L. Y. Zhao et al., Association between Smoking and p53 Mutation in Lung Cancer: A Meta-analysis, Clinical Oncology, vol.26, issue.1, pp.18-24, 2014.
DOI : 10.1016/j.clon.2013.09.003

T. J. Lynch, D. W. Bell, R. Sordella, S. Gurubhagavatula, R. A. Okimoto et al., Activating Mutations in the Epidermal Growth Factor Receptor Underlying Responsiveness of Non???Small-Cell Lung Cancer to Gefitinib, New England Journal of Medicine, vol.350, issue.21, pp.2129-2139, 2004.
DOI : 10.1056/NEJMoa040938

A. Marchetti, L. Felicioni, S. Malatesta, G. Sciarrotta, M. Guetti et al., Mutations, Journal of Clinical Oncology, vol.29, issue.26, pp.3574-3579, 2011.
DOI : 10.1200/JCO.2011.35.9638

C. Mascaux, N. Iannino, B. Martin, M. Paesmans, T. Berghmans et al., The role of RAS oncogene in survival of patients with lung cancer: a systematic review of the literature with meta-analysis, British Journal of Cancer, vol.27, issue.1, pp.131-139, 2005.
DOI : 10.1007/s004320050208

L. Meijer, Le cycle de division cellulaire et sa régulation, Oncol.-PARIS, vol.5, pp.311-326, 2003.

T. S. Mok, Y. Wu, S. Thongprasert, C. Yang, D. Chu et al., Gefitinib or Carboplatin???Paclitaxel in Pulmonary Adenocarcinoma, New England Journal of Medicine, vol.361, issue.10, pp.947-957, 2009.
DOI : 10.1056/NEJMoa0810699

D. Pekin, Y. Skhiri, J. Baret, D. Le-corre, L. Mazutis et al., Quantitative and sensitive detection of rare mutations using droplet-based microfluidics, Lab on a Chip, vol.9, issue.suppl. 4, pp.2156-2166, 2011.
DOI : 10.1039/c1lc20126c

K. Perez-toralla, D. Pekin, J. Bartolo, F. Garlan, P. Nizard et al., PCR digitale en micro-compartiments, m??decine/sciences, vol.31, issue.1, pp.84-92, 2015.
DOI : 10.1051/medsci/20153101017

URL : https://hal.archives-ouvertes.fr/hal-01140226

M. Qiu, J. Wang, Y. Xu, X. Ding, M. Li et al., Circulating Tumor DNA Is Effective for the Detection of EGFR Mutation in Non-Small Cell Lung Cancer: A Meta-analysis, Cancer Epidemiology Biomarkers & Prevention, vol.24, issue.1, pp.206-212, 2015.
DOI : 10.1158/1055-9965.EPI-14-0895

M. W. Schmitt, S. R. Kennedy, J. J. Salk, E. J. Fox, J. B. Hiatt et al., Detection of ultrarare mutations by next-generation sequencing, Proc. Natl. Acad. Sci, pp.14508-14513, 2012.

H. Schwarzenbach, D. S. Hoon, and K. Pantel, Cell-free nucleic acids as biomarkers in cancer patients, Nature Reviews Cancer, vol.61, issue.83, pp.426-437, 2011.
DOI : 10.1038/nrc3066

L. V. Sequist, R. S. Heist, A. T. Shaw, P. Fidias, R. Rosovsky et al., Implementing multiplexed genotyping of non-small-cell lung cancers into routine clinical practice, Annals of Oncology, vol.22, issue.12, pp.2616-2624, 2011.
DOI : 10.1093/annonc/mdr489

L. V. Sequist, B. A. Waltman, D. Dias-santagata, S. Digumarthy, A. B. Turke et al., Genotypic and Histological Evolution of Lung Cancers Acquiring Resistance to EGFR Inhibitors, Science Translational Medicine, vol.105, issue.34, pp.75-101, 2011.
DOI : 10.1073/pnas.0803217105

S. V. Sharma, D. W. Bell, J. Settleman, and D. A. Haber, Epidermal growth factor receptor mutations in lung cancer, Nature Reviews Cancer, vol.64, issue.3, pp.169-181, 2007.
DOI : 10.1038/nrc2088

F. A. Shepherd, J. Rodrigues-pereira, T. Ciuleanu, E. H. Tan, V. Hirsh et al., Erlotinib in Previously Treated Non???Small-Cell Lung Cancer, New England Journal of Medicine, vol.353, issue.2, pp.123-132, 2005.
DOI : 10.1056/NEJMoa050753

R. Sirera, Circulating DNA is a Useful Prognostic Factor in Patients with Advanced Non-small Cell Lung Cancer, Journal of Thoracic Oncology, vol.6, issue.2, 2001.
DOI : 10.1097/JTO.0b013e31820189a5

B. J. Solomon, T. Mok, D. Kim, Y. Wu, K. Nakagawa et al., -Positive Lung Cancer, New England Journal of Medicine, vol.371, issue.23, pp.2167-2177, 2014.
DOI : 10.1056/NEJMoa1408440

URL : https://hal.archives-ouvertes.fr/hal-01009146

M. Stroun, J. Lyautey, C. Lederrey, A. Olson-sand, and P. Anker, About the possible origin and mechanism of circulating DNA, Clinica Chimica Acta, vol.313, issue.1-2, pp.139-142, 2001.
DOI : 10.1016/S0009-8981(01)00665-9

K. Suda, K. Tomizawa, and T. Mitsudomi, Biological and clinical significance of KRAS mutations in lung cancer: an oncogenic driver that contrasts with EGFR mutation, Cancer and Metastasis Reviews, vol.15, issue.238, pp.49-60, 2010.
DOI : 10.1007/s10555-010-9209-4

V. Taly, D. Pekin, A. E. Abed, and P. Laurent-puig, Detecting biomarkers with microdroplet technology, Trends in Molecular Medicine, vol.18, issue.7, pp.405-416, 2012.
DOI : 10.1016/j.molmed.2012.05.001

V. Taly, D. Pekin, L. Benhaim, S. K. Kotsopoulos, D. Le-corre et al., Multiplex Picodroplet Digital PCR to Detect KRAS Mutations in Circulating DNA from the Plasma of Colorectal Cancer Patients, Clinical Chemistry, vol.59, issue.12, pp.1722-1731, 2013.
DOI : 10.1373/clinchem.2013.206359

A. R. Thierry, F. Mouliere, S. Messaoudi, C. Mollevi, E. Lopez-crapez et al., Clinical validation of the detection of KRAS and BRAF mutations from circulating tumor DNA, Nature Medicine, vol.2, issue.4, pp.430-435, 2014.
DOI : 10.1038/nm.3511

C. Tissot, Circulating free DNA concentration is an independent prognostic biomarker in lung cancer, European Respiratory Journal, vol.46, issue.6, 2015.
DOI : 10.1183/13993003.00676-2015

L. Toschi, C. , and F. , Impact of biomarkers on non-small cell lung cancer treatment, Targeted Oncology, vol.104, issue.52, pp.5-17, 2010.
DOI : 10.1007/s11523-010-0132-y

D. W. Tsui and M. F. Berger, Profiling Non-Small Cell Lung Cancer: From Tumor to Blood, Clinical Cancer Research, vol.22, issue.4, 2016.
DOI : 10.1158/1078-0432.CCR-15-2514

URL : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4852855

D. W. Tsui and M. F. Berger, Profiling Non-Small Cell Lung Cancer: From Tumor to Blood, Clinical Cancer Research, vol.22, issue.4, 2016.
DOI : 10.1158/1078-0432.CCR-15-2514

URL : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4852855

M. Van-der-vaart and P. J. Pretorius, Circulating DNA, Annals of the New York Academy of Sciences, vol.23, issue.Suppl A, pp.18-26, 2008.
DOI : 10.1196/annals.1448.022

A. Vallée, C. Audigier-valette, G. Herbreteau, J. Merrien, L. Tessonnier et al., Rapid clearance of circulating tumor DNA during treatment with AZD9291 of a lung cancer patient presenting the resistance EGFR T790M mutation, Lung Cancer, vol.91, pp.73-74, 2016.
DOI : 10.1016/j.lungcan.2015.11.008

K. Wong, Searching for a magic bullet in NSCLC: the role of epidermal growth factor receptor mutations and tyrosine kinase inhibitors, Lung Cancer, vol.60, issue.2, pp.10-18, 2008.
DOI : 10.1016/S0169-5002(08)70100-4

K. Yoon, S. Park, S. H. Lee, J. H. Kim, L. et al., Comparison of Circulating Plasma DNA Levels between Lung Cancer Patients and Healthy Controls, The Journal of Molecular Diagnostics, vol.11, issue.3, pp.182-185, 2009.
DOI : 10.2353/jmoldx.2009.080098

Q. Zhong, S. Bhattacharya, S. Kotsopoulos, J. Olson, V. Taly et al., Multiplex digital PCR: breaking the one target per color barrier of quantitative PCR, Lab on a Chip, vol.15, issue.13, pp.2167-2174, 2011.
DOI : 10.1039/c1lc20128j

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