.. Quantité, 83 a) Nombre de cellules tumorales, 83 b) Proportion de cellules tumorales et surface du prélèvement, p.83

I. C. Weinstein, T. Lynch, D. Bell, R. Sordella, S. Gurubhagavatula et al., Addiction to oncogenes--the Achilles heal of cancer Activating mutations in the epidermal growth factor receptor underlying responsiveness of nonsmall-cell lung cancer to gefitinib, Science. 5 juill N Engl J Med, vol.297350, issue.5578 221, pp.2129-2168, 2002.

N. Guibert, M. Ilie, H. Léna, A. Didier, P. Hofman et al., KRAS and bronchial adenocarcinoma. Between disappointments and hopes], Rev Mal Respir. 5 nov, 2015.

J. Mazières, S. Peters, B. Lepage, A. Cortot, F. Barlesi et al., Mutation: Epidemiologic Characteristics and Therapeutic Perspectives, Journal of Clinical Oncology, vol.31, issue.16, 2013.
DOI : 10.1200/JCO.2012.45.6095

M. Soda, Y. Choi, M. Enomoto, S. Takada, Y. Yamashita et al., Identification of the transforming EML4???ALK fusion gene in non-small-cell lung cancer, Nature, vol.276, issue.7153, pp.561-567, 2007.
DOI : 10.1038/nature05945

K. Rikova, A. Guo, Q. Zeng, A. Possemato, J. Yu et al., Global Survey of Phosphotyrosine Signaling Identifies Oncogenic Kinases in Lung Cancer, Cell, vol.131, issue.6, pp.1190-203, 2007.
DOI : 10.1016/j.cell.2007.11.025

K. Takeuchi, M. Soda, Y. Togashi, R. Suzuki, S. Sakata et al., RET, ROS1 and ALK fusions in lung cancer, Nature Medicine, vol.344, issue.3, pp.378-81, 2012.
DOI : 10.1158/0008-5472.CAN-08-2014

T. Kohno, H. Ichikawa, Y. Totoki, K. Yasuda, M. Hiramoto et al., KIF5B-RET fusions in lung adenocarcinoma, Nature Medicine, vol.62, issue.3, pp.375-382, 2012.
DOI : 10.2165/11595310-000000000-00000

K. Yokota, H. Sasaki, K. Okuda, S. Shimizu, M. Shitara et al., RET fusion gene in surgically-treated adenocarcinoma of the lung Disponible sur: http://globocan.iarc.fr/Pages/fact_sheets_population.aspx 11 WHO Pathology and genetics of tumors of the lung, pleura, thymus and heart, ):1187?92. 10. IARC. Globocan 2012 12. INCa. Les cancers en France, Les Données. 2015. 13. INCa. Les cancers en France en 2014, L'essentiel des faits et chiffres, 2004.

D. Coëtmeur, G. Leveiller, V. Frappat, M. Martin, M. Peureux et al., Relationship between primary lung cancer and tobacco consumption. Results of the KBP-2010-CPHG study by the French College of General Hospital Respiratory Physicians]. Rev Mal Respir. 24 nov 2015 WHO classification of tumors of the lung, pleura, thymus and heart Lyon: IARC; 2015. 16. World Health Organisation Genomic architecture of lung cancers, al. International association for the study of lung cancer, pp.52-59, 2008.

R. Lassalle and I. , Tumeurs neuroendocrines pulmonaires et l??sions pr??n??oplasiques, Annales de Pathologie, vol.36, issue.1, pp.34-43, 2016.
DOI : 10.1016/j.annpat.2015.11.008

F. Hirsch, M. Wynes, D. Gandara, and P. Bunn, The Tissue Is the Issue: Personalized Medicine for Non-Small Cell Lung Cancer, 4909?11. 22. Union Internationale Contre le Cancer. TNM, classification des tumeurs malignes, 2010.
DOI : 10.1158/1078-0432.CCR-10-2005

. Cassini, 23. INCa. Cancer bronchique non à petites cellules, référentiel national de RCP, 2010.

F. Penault-llorca, L. Tixier, L. Perrot, C. A. Viala, M. Varga et al., Strategy for molecular testing in pulmonary carcinoma] [3rd generation's TKI in lung cancer non-small cell EGFR-mutated having acquired a secondary T790M resistance], Ann Pathol. janv Bull Cancer sept, vol.36102, issue.19, pp.749-57, 2015.

D. Hanahan and R. Weinberg, Hallmarks of Cancer: The Next Generation, Cell, vol.144, issue.5, pp.646-74, 2011.
DOI : 10.1016/j.cell.2011.02.013

B. Vogelstein, N. Papadopoulos, V. Velculescu, S. Zhou, L. Diaz et al., Mutational landscape and significance across 12 major cancer types Genomic landscape of non-small cell lung cancer in smokers and never-smokers. Cell, 1546?58. 28. Kandoth C, pp.1121-1155, 2012.

J. Seo, Y. Ju, W. Lee, J. Shin, J. Lee et al., The transcriptional landscape and mutational profile of lung adenocarcinoma, Genome Research, vol.22, issue.11, pp.2109-2128, 2012.
DOI : 10.1101/gr.145144.112

F. Barlesi, J. Mazieres, J. Merlio, D. Debieuvre, J. Mosser et al., Routine molecular profiling of patients with advanced non-small-cell lung cancer: results of a 1-year nationwide programme of the French Cooperative Thoracic Intergroup (IFCT) Lancet Lond Engl 14 janv 2016A simple view on lung cancer biology: The EGFR pathway] Epidermal growth factor receptor mutations in lung cancer):169?81. 34. Roukos V, Misteli T. The biogenesis of chromosome translocations, 293?300. 35. Pan Y al. ALK, ROS1 and RET fusions in 1139 lung adenocarcinomas: a comprehensive study of common and fusion pattern-specific clinicopathologic, histologic and cytologic features. Lung Cancer Amst Neth, pp.565-77, 2007.

S. Jancík, J. Drábek, D. Radzioch, M. Hajdúch, S. Devarakonda et al., Clinical relevance of KRAS in human cancers, Genomic alterations in lung adenocarcinoma, pp.150960-150997, 2010.

L. Villaruz, M. Socinski, D. Cunningham, S. Chiosea, T. Burns et al., The prognostic and predictive value of KRAS oncogene substitutions in lung adenocarcinoma, Cancer. 15 juin, vol.119, issue.12, pp.2268-74, 2013.

Y. Ohtaki, K. Shimizu, S. Kakegawa, T. Nagashima, T. Nakano et al., Postrecurrence survival of surgically resected pulmonary adenocarcinoma patients according to EGFR and KRAS mutation status, Mol Clin Oncol. mars, vol.2, issue.2, pp.187-96, 2014.

J. Mazières, F. Barlesi, T. Filleron, B. Besse, I. Monnet et al., Lung cancer patients with HER2 mutations treated with chemotherapy and HER2-targeted drugs: Results from the European EUHER2 cohort, Ann Oncol Off J Eur Soc Med Oncol ESMO. 23 nov, vol.41, 2015.

D. Rouviere, E. Bousquet, E. Pons, J. Milia, N. Guibert et al., Nouvelles cibles et nouvelles mol??cules en oncologie thoracique, Revue des Maladies Respiratoires, vol.32, issue.8, pp.867-76, 2015.
DOI : 10.1016/j.rmr.2015.02.091

O. Gautschi, C. Pauli, K. Strobel, A. Hirschmann, G. Printzen et al., A Patient With BRAF V600E Lung Adenocarcinoma Responding to Vemurafenib, Journal of Thoracic Oncology, vol.7, issue.10, pp.23-24, 2012.
DOI : 10.1097/JTO.0b013e3182629903

S. Peters, O. Michielin, and S. Zimmermann, V600E-Mutated Lung Adenocarcinoma, Journal of Clinical Oncology, vol.31, issue.20, pp.341-344, 2013.
DOI : 10.1200/JCO.2012.47.6143

S. Robinson, O. Shaughnessy, J. Cowey, C. Konduri, and K. , BRAF V600E-mutated lung adenocarcinoma with metastases to the brain responding to treatment with vemurafenib, Lung Cancer, vol.85, issue.2, pp.326-356, 2014.
DOI : 10.1016/j.lungcan.2014.05.009

D. Hyman, I. Puzanov, V. Subbiah, J. Faris, I. Chau et al., Interim results of phase II study BRF113928 of dabrafenib in BRAF V600E mutation-positive non-small cell lung cancer (NSCLC) patients. ASCO Meet Abstr):8009. 47A simple view on lung cancer biology: the MET pathway] Disponible sur: http://www.e-cancer.fr/Professionnels-de-la-recherche/Recherche- clinique/Le-programme-AcSe2/AcSe-crizotinib 49. Les plateformes de génétique moléculaire des cancers -Les thérapies ciblées | Institut National Du Cancersante/Les-therapies-ciblees/Les-plateformes-de-genetique-moleculaire- des-cancers 50, Multiple Nonmelanoma Cancers with BRAF V600 Mutations1241?9. 48. AcSé crizotinib -Le programme AcSé | Institut National Du Cancer [Internet]. [cité 23 nov 2015], pp.726-762, 2011.

Z. Zhao, V. Verma, and M. Zhang, Anaplastic lymphoma kinase: Role in cancer and therapy perspective, Cancer Biology & Therapy, vol.31, issue.12, 2015.
DOI : 10.1200/JCO.2013.49.4757

R. Palmer, E. Vernersson, C. Grabbe, B. Hallberg, C. Voena et al., Anaplastic lymphoma kinase: signalling in development and disease The anaplastic lymphoma kinase as an oncogene in solid tumors, Biochem J. 15 juin, vol.420, issue.3, pp.345-61, 2009.

F. Biosci-sch, E. 5. Shackelford, R. Vora, M. Mayhall, K. Cotelingam et al., ALK-rearrangements and testing methods in non-small cell lung cancer: a review Crizotinib for the treatment of ALKrearranged non-small cell lung cancer: a success story to usher in the second decade of molecular targeted therapy in oncology, 1?2):1?14. 55. Ou S, pp.1351-75, 2012.

E. Chan, C. Chin, and V. Lui, An update of ALK inhibitors in human clinical trials, Future Oncology, vol.12, issue.1, 2015.
DOI : 10.2217/fon.15.293

R. Chiarle, C. Voena, C. Ambrogio, R. Piva, G. Inghirami et al., The anaplastic lymphoma kinase in the pathogenesis of cancer Anaplastic lymphoma kinase in human cancer, Nat Rev Cancer. janv J Mol Endocrinol. août, vol.847, issue.11, pp.11-23, 2008.

Y. Choi, M. Lira, M. Hong, R. Kim, S. Choi et al., A Novel Fusion of TPR and ALK in Lung Adenocarcinoma, Journal of Thoracic Oncology, vol.9, issue.4, pp.563-569, 2014.
DOI : 10.1097/JTO.0000000000000093

Y. Togashi, M. Soda, S. Sakata, E. Sugawara, S. Hatano et al., KLC1-ALK: A Novel Fusion in Lung Cancer Identified Using a Formalin-Fixed Paraffin-Embedded Tissue Only, PLoS ONE, vol.12, issue.2, p.31323, 2012.
DOI : 10.1371/journal.pone.0031323.s002

D. Wong, E. Leung, S. Wong, V. Tin, A. Sihoe et al., A novel KIF5B- ALK variant in nonsmall cell lung cancer, Cancer. 15 juin, vol.117, issue.12, pp.2709-2727, 2011.

L. Shan, P. Jiang, F. Xu, W. Zhang, L. Guo et al., BIRC6-ALK, a Novel Fusion Gene in ALK Break-Apart FISH-Negative Lung Adenocarcinoma, Responds to Crizotinib Detection of ALK rearrangement by immunohistochemistry in lung adenocarcinoma and the identification of a novel EML4-ALK variant Exon scanning by reverse transcriptase-polymerase chain reaction for detection of known and novel EML4-ALK fusion variants in non-small cell lung cancerALK, a novel ALK fusion variant that responds to crizotinib, 45?52. 65. Fang DD, pp.37-39285, 2011.

M. Hong, R. Kim, J. Song, S. Choi, E. Oh et al., HIP1???ALK, a Novel Fusion Protein Identified in Lung Adenocarcinoma, Journal of Thoracic Oncology, vol.9, issue.3, pp.419-441, 2014.
DOI : 10.1097/JTO.0000000000000061

S. Ou, S. Klempner, J. Greenbowe, M. Azada, A. Schrock et al., Identification of a Novel HIP1-ALK Fusion Variant in Non???Small-Cell Lung Cancer (NSCLC) and Discovery of ALK I1171 (I1171N/S) Mutations in Two ALK-Rearranged NSCLC Patients with Resistance to Alectinib, 1821?5. 68. Iyevleva AG, pp.116-137, 2014.
DOI : 10.1097/JTO.0000000000000368

R. Kim, Y. Choi, M. Lee, M. Lira, M. Mao et al., SEC31A-ALK Fusion Gene in Lung Adenocarcinoma A novel EML4-ALK variant: exon 6 of EML4 fused to exon 19 of ALK, Cancer Res Treat Off J Korean Cancer Assoc. 17 févr J Thorac Oncol Off Publ Int Assoc Study Lung Cancer. juill, vol.707, issue.7, pp.1198-1207, 2012.

R. Wang, Y. Pan, C. Li, H. Hu, Y. Zhang et al., The Use of Quantitative Real-Time Reverse Transcriptase PCR for 5' and 3' Portions of ALK Transcripts to Detect ALK Rearrangements in Lung Cancers, Clinical Cancer Research, vol.18, issue.17, pp.4725-4757, 2012.
DOI : 10.1158/1078-0432.CCR-12-0677

K. Takeuchi, Y. Choi, Y. Togashi, M. Soda, S. Hatano et al., KIF5B-ALK, a Novel Fusion Oncokinase Identified by an Immunohistochemistry-based Diagnostic System for ALK-positive Lung Cancer, Clinical Cancer Research, vol.15, issue.9, pp.3143-3152, 2009.
DOI : 10.1158/1078-0432.CCR-08-3248

Y. Jung, P. Kim, Y. Jung, J. Keum, S. Kim et al., Discovery of ALK-PTPN3 gene fusion from human non-small cell lung carcinoma cell line using next generation RNA sequencing, Genes, Chromosomes and Cancer, vol.304, issue.6, pp.590-597, 2012.
DOI : 10.1002/gcc.21945

S. Morris, M. Kirstein, M. Valentine, K. Dittmer, D. Shapiro et al., Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma Unique Clinicopathologic Features Characterize ALK-Rearranged Lung Adenocarcinoma in the Western Population, 1281?4. 75. Rodig SJ, pp.5216-5239, 1994.

R. Doebele, X. Lu, C. Sumey, D. Maxson, A. Weickhardt et al., Oncogene status predicts patterns of metastatic spread in treatment-naive nonsmall cell lung cancer. Cancer. 15 sept 2012 Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer, 4502?11. 77. Kwak EL, pp.1693-703, 2010.

D. Camidge, Y. Bang, E. Kwak, A. Iafrate, M. Varella-garcia et al., Activity and safety of crizotinib in patients with ALK-positive non-small-cell lung cancer: updated results from a phase 1 study Comprehensive histologic analysis of ALK-rearranged lung carcinomas Clinical features and outcome of patients with non-small-cell lung cancer who harbor EML4-ALK, ):1011?9. 79. Yoshida A,1226?34. 80. Shaw AT,4247?53. 81. Toyokawa G, Seto T. Anaplastic lymphoma kinase rearrangement in lung cancer: its biological and clinical significance. Respir Investig, pp.330-338, 2009.

M. Tsao, F. Hirsch, and Y. Yatabe, IASLC Atlas of ALK Testing in Lung Cancer. IASLC press, 2013.

H. Kim, X. Xu, S. Yoo, P. Sun, J. Y. Paik et al., Discordance between anaplastic lymphoma kinase status in primary non-small-cell lung cancers and their corresponding metastases, Histopathology, vol.51, issue.2, pp.305-319, 2013.
DOI : 10.1111/j.1365-2559.2012.04356.x

V. Martin, B. Bernasconi, E. Merlo, P. Balzarini, W. Vermi et al., ALK Testing in Lung Adenocarcinoma: Technical Aspects to Improve FISH Evaluation in Daily Practice, Journal of Thoracic Oncology, vol.10, issue.4, pp.595-602, 2015.
DOI : 10.1097/JTO.0000000000000444

J. Zhou, J. Zhao, K. Sun, B. Wang, L. Wang et al., Accurate and Economical Detection of ALK Positive Lung Adenocarcinoma with Semiquantitative Immunohistochemical Screening, PLoS ONE, vol.12, issue.3, p.92828, 2014.
DOI : 10.1371/journal.pone.0092828.s004

T. Sasaki, J. Koivunen, A. Ogino, M. Yanagita, S. Nikiforow et al., A novel ALK secondary mutation and EGFR signaling cause resistance to ALK kinase inhibitors. Cancer Res. 15 sept ALK rearrangements are mutually exclusive with mutations in EGFR or KRAS: an analysis of 1,683 patients with non-small cell lung cancer, Clin Cancer Res Off J Am Assoc Cancer Res. 1 août, vol.7119, issue.8715, pp.4273-81, 2011.

W. Cooper, S. Fox, O. Toole, S. Morey, A. Frances et al., National Working Group Meeting on ALK diagnostics in lung cancer, Asia-Pacific Journal of Clinical Oncology, vol.8, issue.2, pp.11-18, 2014.
DOI : 10.1111/ajco.12190

D. Camidge, S. Kono, X. Lu, S. Okuyama, A. Barón et al., Anaplastic lymphoma kinase gene rearrangements in non-small cell lung cancer are associated with prolonged progressionfree survival on pemetrexed, 774?80. 90. Crescenzo R, Inghirami G. Anaplastic lymphoma kinase inhibitors, pp.39-44, 2011.

D. Camidge, M. Skokan, P. Kiatsimkul, B. Helfrich, X. Lu et al., Native and rearranged ALK copy number and rearranged cell count in non-small cell lung cancer, Cancer, vol.18, issue.suppl, pp.3968-75, 2013.
DOI : 10.1002/cncr.28311

D. Camidge, W. Pao, and L. Sequist, Acquired resistance to TKIs in solid tumours: learning from lung cancer, Nature Reviews Clinical Oncology, vol.27, issue.8, pp.473-81, 2014.
DOI : 10.1016/S1470-2045(13)70311-5

B. Liao, C. Lin, J. Shih, and J. Yang, -positive non-small cell lung cancer: latest evidence and management strategy, Therapeutic Advances in Medical Oncology, vol.12, issue.5, pp.274-90, 2015.
DOI : 10.1038/nrc2887

URL : https://hal.archives-ouvertes.fr/hal-00309089

C. Hamard, A. Ruppert, A. Lavole, N. Rozensztajn, M. Antoine et al., Actualit??s sur les th??rapies cibl??es dans les cancers bronchiques non ?? petites cellules, hors immunoth??rapie, Annales de Pathologie, vol.36, issue.1, pp.63-72, 2016.
DOI : 10.1016/j.annpat.2015.11.002

D. Camidge, M. Theodoro, D. Maxson, M. Skokan, O. Brien et al., Correlations between the percentage of tumor cells showing an anaplastic lymphoma kinase (ALK) gene rearrangement, ALK signal copy number, and response to crizotinib therapy in ALK fluorescence in situ hybridizationpositive nonsmall cell lung cancer al. Increased ALK gene copy number and amplification are frequent in non-small cell lung cancer, 4486?94. 96. Salido M, pp.21-28, 2011.

J. Heuckmann, H. Balke-want, F. Malchers, M. Peifer, M. Sos et al., Differential protein stability and ALK inhibitor sensitivity of EML4-ALK fusion variants Clin Cancer Res Off J Am Assoc Cancer Res ROS1 rearrangements define a unique molecular class of lung cancers, 4682?90. 98. Bergethon K, pp.863-70, 2012.

J. Acquaviva, R. Wong, and A. Charest, The multifaceted roles of the receptor tyrosine kinase ROS in development and cancer, Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, vol.1795, issue.1, pp.37-52, 2009.
DOI : 10.1016/j.bbcan.2008.07.006

A. Shaw, S. Ou, Y. Bang, D. Camidge, B. Solomon et al., -Rearranged Non???Small-Cell Lung Cancer, New England Journal of Medicine, vol.371, issue.21, pp.1963-71, 2014.
DOI : 10.1056/NEJMoa1406766

URL : https://hal.archives-ouvertes.fr/in2p3-00459276

J. Gainor and A. Shaw, Novel Targets in Non-Small Cell Lung Cancer: ROS1 and RET Fusions, The Oncologist, vol.18, issue.7, pp.865-75, 2013.
DOI : 10.1634/theoncologist.2013-0095

S. Ou, Z. Chalmers, M. Azada, J. Ross, P. Stephens et al., Identification of a novel TMEM106B-ROS1 fusion variant in lung adenocarcinoma by comprehensive genomic profiling, Lung Cancer, vol.88, issue.3, pp.352-356, 2015.
DOI : 10.1016/j.lungcan.2015.03.014

W. Cai, X. Li, C. Su, L. Fan, L. Zheng et al., ROS1 fusions in Chinese patients with non-small-cell lung cancer, Annals of Oncology, vol.24, issue.7, pp.1822-1829, 2013.
DOI : 10.1093/annonc/mdt071

V. Rimkunas, K. Crosby, D. Li, Y. Hu, M. Kelly et al., Analysis of Receptor Tyrosine Kinase ROS1-Positive Tumors in Non-Small Cell Lung Cancer: Identification of a FIG-ROS1 Fusion, Clinical Cancer Research, vol.18, issue.16, pp.4449-57, 2012.
DOI : 10.1158/1078-0432.CCR-11-3351

Y. Suehara, M. Arcila, L. Wang, A. Hasanovic, D. Ang et al., Identification of KIF5B-RET and GOPC-ROS1 Fusions in Lung Adenocarcinomas through a Comprehensive mRNA-Based Screen for Tyrosine Kinase Fusions, Clinical Cancer Research, vol.18, issue.24, pp.6599-608, 2012.
DOI : 10.1158/1078-0432.CCR-12-0838

K. Davies and R. Doebele, Molecular Pathways: ROS1 Fusion Proteins in Cancer, Clinical Cancer Research, vol.19, issue.15, pp.4040-4045, 2013.
DOI : 10.1158/1078-0432.CCR-12-2851

H. Jun, H. Johnson, R. Bronson, S. De-feraudy, F. White et al., The Oncogenic Lung Cancer Fusion Kinase CD74-ROS Activates a Novel Invasiveness Pathway through E-Syt1 Phosphorylation, Cancer Research, vol.72, issue.15
DOI : 10.1158/0008-5472.CAN-11-3990

A. Warth, T. Muley, H. Dienemann, B. Goeppert, A. Stenzinger et al., expression and translocations in non-small-cell lung cancer: clinicopathological analysis of 1478 cases, Histopathology, vol.24, issue.2, pp.187-94, 2014.
DOI : 10.1111/his.12379

Y. Jin, P. Sun, H. Kim, E. Park, H. Shim et al., ROS1 gene rearrangement and copy number gain in non-small cell lung cancer, Virchows Archiv, vol.20, issue.1, pp.45-52, 2015.
DOI : 10.1007/s00428-014-1679-2

M. Scheffler, A. Schultheis, C. Teixido, S. Michels, D. Morales-espinosa et al., ROS1 rearrangements in lung adenocarcinoma: prognostic impact, therapeutic options and genetic variability, Oncotarget, vol.6, issue.12, pp.10577-85, 2015.
DOI : 10.18632/oncotarget.3387

H. Kim, S. Lim, H. Kim, S. Hwang, J. Park et al., The frequency and impact of ROS1 rearrangement on clinical outcomes in never smokers with lung adenocarcinoma, Annals of Oncology, vol.24, issue.9, pp.2364-70, 2013.
DOI : 10.1093/annonc/mdt220

H. Go, D. Kim, D. Kim, B. Keam, T. Kim et al., Clinicopathologic Analysis of ROS1-Rearranged Non???Small-Cell Lung Cancer and Proposal of a Diagnostic Algorithm, Journal of Thoracic Oncology, vol.8, issue.11, pp.1445-50, 2013.
DOI : 10.1097/JTO.0b013e3182a4dd6e

W. Cai, W. Li, S. Ren, L. Zheng, X. Li et al., Coexistence of Three Variants Involving Two Different Fusion Partners of ROS1 Including a Novel Variant of ROS1 Fusions in Lung Adenocarcinoma: A Case Report, Journal of Thoracic Oncology, vol.9, issue.6, pp.43-46, 2014.
DOI : 10.1097/JTO.0000000000000118

H. Lee, H. Seol, J. Kim, S. Chun, Y. Suh et al., ROS1 Receptor Tyrosine Kinase, a Druggable Target, is Frequently Overexpressed in Non-Small Cell Lung Carcinomas Via Genetic and Epigenetic Mechanisms, Annals of Surgical Oncology, vol.455, issue.1, pp.200-208, 2013.
DOI : 10.1245/s10434-012-2553-6

C. Birchmeier, S. Sharma, and M. Wigler, Expression and rearrangement of the ROS1 gene in human glioblastoma cells., Proceedings of the National Academy of Sciences, vol.84, issue.24, pp.9270-9274, 1987.
DOI : 10.1073/pnas.84.24.9270

A. Charest, K. Lane, K. Mcmahon, J. Park, E. Preisinger et al., Fusion of FIG to the receptor tyrosine kinase ROS in a glioblastoma with an interstitial del(6)(q21q21), Genes, Chromosomes and Cancer, vol.73, issue.1, pp.58-71, 2003.
DOI : 10.1002/gcc.10207

Q. Zhu, P. Zhan, X. Zhang, T. Lv, and Y. Song, Clinicopathologic characteristics of patients with ROS1 fusion gene in non-small cell lung cancer: a meta-analysis, Transl Lung Cancer Res. juin, vol.4, issue.3, pp.300-309, 2015.

S. Clavé, J. Gimeno, A. Muñoz-mármol, J. Vidal, N. Reguart et al., ROS1 copy number alterations are frequent in non-small cell lung cancer, Oncotarget. 15 janv, 2016.

T. Gu, X. Deng, F. Huang, M. Tucker, K. Crosby et al., Survey of Tyrosine Kinase Signaling Reveals ROS Kinase Fusions in Human Cholangiocarcinoma, PLoS ONE, vol.10, issue.1, p.15640, 2011.
DOI : 10.1371/journal.pone.0015640.s004

J. Lee, S. Lee, S. Kang, I. Do, S. Lee et al., Identification of ROS1 rearrangement in gastric adenocarcinoma, Cancer. 1 mai, vol.119, issue.9, pp.1627-1662, 2013.

A. Birch, S. Arcand, K. Oros, K. Rahimi, A. Watters et al., Chromosome 3 Anomalies Investigated by Genome Wide SNP Analysis of Benign, Low Malignant Potential and Low Grade Ovarian Serous Tumours, PLoS ONE, vol.43, issue.12, p.28250, 2011.
DOI : 10.1371/journal.pone.0028250.s003

L. Mescam-mancini, S. Lantuéjoul, D. Moro-sibilot, I. Rouquette, P. Souquet et al., On the relevance of a testing algorithm for the detection of ROS1-rearranged lung adenocarcinomas, Lung Cancer, vol.83, issue.2, pp.168-73, 2014.
DOI : 10.1016/j.lungcan.2013.11.019

L. Sholl, H. Sun, M. Butaney, C. Zhang, C. Lee et al., ROS1 Immunohistochemistry for Detection of ROS1-Rearranged Lung Adenocarcinomas, The American Journal of Surgical Pathology, vol.37, issue.9, pp.1441-1450, 2013.
DOI : 10.1097/PAS.0b013e3182960fa7

T. Boyle, K. Masago, K. Ellison, Y. Yatabe, and F. Hirsch, ROS1 Immunohistochemistry Among Major Genotypes of Non???Small-Cell Lung Cancer, Clinical Lung Cancer, vol.16, issue.2, pp.106-117, 2015.
DOI : 10.1016/j.cllc.2014.10.003

Y. Chen, M. Hsieh, S. Wu, Y. Chang, J. Shih et al., Clinical and the Prognostic Characteristics of Lung Adenocarcinoma Patients with ROS1 Fusion in Comparison with Other Driver Mutations in East Asian Populations, Journal of Thoracic Oncology, vol.9, issue.8, pp.1171-1180, 2014.
DOI : 10.1097/JTO.0000000000000232

M. Bos, M. Gardizi, H. Schildhaus, R. Buettner, and J. Wolf, Activated RET and ROS: two new driver mutations in lung adenocarcinoma, Transl Lung Cancer Res. avr, vol.2, issue.2, pp.112-133, 2013.

J. Mazières, G. Zalcman, L. Crinò, P. Biondani, F. Barlesi et al., Rearrangement: Results From the EUROS1 Cohort, Journal of Clinical Oncology, vol.33, issue.9, pp.992-1001, 2015.
DOI : 10.1200/JCO.2014.58.3302

A. Drilon, R. Somwar, J. Wagner, N. Vellore, C. Eide et al., A novel crizotinibresistant solvent-front mutation responsive to cabozantinib therapy in a patient with ROS1- rearranged lung cancer, Clin Cancer Res Off J Am Assoc Cancer Res. 16 déc, 2015.

A. Song, T. Kim, D. Kim, S. Kim, B. Keam et al., Molecular Changes Associated with Acquired Resistance to Crizotinib in ROS1-Rearranged Non-Small Cell Lung Cancer, Clinical Cancer Research, vol.21, issue.10, pp.2379-87, 2015.
DOI : 10.1158/1078-0432.CCR-14-1350

M. Cargnelutti, S. Corso, M. Pergolizzi, L. Mévellec, D. Aisner et al., Activation of RAS family members confers resistance to ROS1 targeting drugs, Oncotarget, vol.6, issue.7, pp.5182-94, 2015.
DOI : 10.18632/oncotarget.3311

M. Davare, N. Vellore, J. Wagner, C. Eide, J. Goodman et al., Structural insight into selectivity and resistance profiles of ROS1 tyrosine kinase inhibitors, Proceedings of the National Academy of Sciences, vol.112, issue.39, pp.5381-5390, 2015.
DOI : 10.1073/pnas.1515281112

M. Borrello, E. Ardini, L. Locati, A. Greco, L. Licitra et al., RET inhibition: implications in cancer therapy, Expert Opinion on Therapeutic Targets, vol.10, issue.24, pp.403-422, 2013.
DOI : 10.1056/NEJMoa075853

C. Lin, S. Wang, W. Xie, J. Chang, and Y. Gan, The RET fusion gene and its correlation with demographic and clinicopathological features of non-small cell lung cancer: a meta-analysis, Cancer Biology & Therapy, vol.28, issue.4, pp.1019-1047, 2015.
DOI : 10.1097/JTO.0000000000000234

M. Lira, Y. Choi, S. Lim, S. Deng, D. Huang et al., A Single-Tube Multiplexed Assay for Detecting ALK, ROS1, and RET Fusions in Lung Cancer, The Journal of Molecular Diagnostics, vol.16, issue.2, pp.229-272, 2014.
DOI : 10.1016/j.jmoldx.2013.11.007

A. Drilon, L. Wang, A. Hasanovic, Y. Suehara, D. Lipson et al., Fusion-Positive Lung Adenocarcinomas, Cancer Discovery, vol.3, issue.6, pp.630-635, 2013.
DOI : 10.1158/2159-8290.CD-13-0035

Y. Ju, W. Lee, J. Shin, S. Lee, T. Bleazard et al., A transforming KIF5B and RET gene fusion in lung adenocarcinoma revealed from whole-genome and transcriptome sequencing, Genome Research, vol.22, issue.3
DOI : 10.1101/gr.133645.111

S. Lee, B. Lee, M. Hong, J. Song, K. Jung et al., Comprehensive analysis of RET and ROS1 rearrangement in lung adenocarcinoma, Modern Pathology, vol.1795, issue.4, pp.468-79, 2015.
DOI : 10.1097/JTO.0b013e318274a83e

S. Michels, A. Scheel, M. Scheffler, A. Schultheis, O. Gautschi et al., Clinicopathological Characteristics of RET Rearranged Lung Cancer in European Patients, Journal of Thoracic Oncology, vol.11, issue.1, pp.122-129, 2016.
DOI : 10.1016/j.jtho.2015.09.016

D. Lipson, M. Capelletti, R. Yelensky, G. Otto, A. Parker et al., Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies, Nature Medicine, vol.18, issue.3, pp.382-386, 2012.
DOI : 10.1158/1078-0432.CCR-07-1772

A. Fusco, M. Grieco, M. Santoro, M. Berlingieri, S. Pilotti et al., A new oncogene in human thyroid papillary carcinomas and their lymph-nodal metastases, Nature, vol.328, issue.6126, pp.170-172, 1987.
DOI : 10.1038/328170a0

M. Gournay, S. Médane, F. Dugay, F. Llamas-gutierrez, M. Belaud-rotureau et al., Etude du réarrangement du gène RET dans les adénocarcinomes pulmonaires. Poster présenté à: 20es journées du collège des histologistes, embryologistes et cytogénéticiens; 2015 mars

S. Mukhopadhyay, N. Pennell, S. Ali, J. Ross, P. Ma et al., RET-Rearranged Lung Adenocarcinomas with Lymphangitic Spread, Psammoma Bodies, and Clinical Responses to Cabozantinib, Journal of Thoracic Oncology, vol.9, issue.11, pp.1714-1723, 2014.
DOI : 10.1097/JTO.0000000000000323

W. Cai, C. Su, X. Li, L. Fan, L. Zheng et al., fusions in Chinese patients with non-small cell lung cancer, Cancer, vol.68, issue.18S, pp.1486-94, 2013.
DOI : 10.1002/cncr.27940

T. Tsai, S. Wu, M. Hsieh, C. Yu, J. Yang et al., Clinical and prognostic implications of RET rearrangements in metastatic lung adenocarcinoma patients with malignant pleural effusion, Lung Cancer, vol.88, issue.2, pp.208-222, 2015.
DOI : 10.1016/j.lungcan.2015.02.018

S. Dacic, A. Luvison, V. Evdokimova, L. Kelly, J. Siegfried et al., RET Rearrangements in Lung Adenocarcinoma and Radiation, Journal of Thoracic Oncology, vol.9, issue.1, pp.118-138, 2014.
DOI : 10.1097/JTO.0000000000000015

S. Klempner, L. Bazhenova, F. Braiteh, P. Nikolinakos, K. Gowen et al., Emergence of RET rearrangement co-existing with activated EGFR mutation in EGFR -mutated NSCLC patients who had progressed on first- or second-generation EGFR TKI, Lung Cancer, vol.89, issue.3, pp.357-366, 2015.
DOI : 10.1016/j.lungcan.2015.06.021

O. Gautschi, T. Zander, F. Keller, K. Strobel, A. Hirschmann et al., A Patient with Lung Adenocarcinoma and RET Fusion Treated with Vandetanib, Journal of Thoracic Oncology, vol.8, issue.5, pp.43-44, 2013.
DOI : 10.1097/JTO.0b013e31828a4d07

T. Kodama, T. Tsukaguchi, Y. Satoh, M. Yoshida, Y. Watanabe et al., Alectinib Shows Potent Antitumor Activity against RET-Rearranged Non-Small Cell Lung Cancer, Molecular Cancer Therapeutics, vol.13, issue.12, pp.2910-2918, 2014.
DOI : 10.1158/1535-7163.MCT-14-0274

F. Lin and Z. Chen, Standardization of Diagnostic Immunohistochemistry: Literature Review and Geisinger Experience, Archives of Pathology & Laboratory Medicine, vol.138, issue.12, pp.1564-77, 2014.
DOI : 10.5858/arpa.2014-0074-RA

J. Gruchy, P. Barnes, D. Haché, and K. , CytoLyt?? Fixation and Decalcification Pretreatments Alter Antigenicity in Normal Tissues Compared With Standard Formalin Fixation, Applied Immunohistochemistry & Molecular Morphology, vol.23, issue.4, pp.297-302, 2015.
DOI : 10.1097/PAI.0000000000000082

A. Mcleer-florin, D. Moro-sibilot, A. Melis, D. Salameire, C. Lefebvre et al., Dual IHC and FISH Testing for ALK Gene Rearrangement in Lung Adenocarcinomas in a Routine Practice: A French Study, Journal of Thoracic Oncology, vol.7, issue.2, pp.348-54, 2012.
DOI : 10.1097/JTO.0b013e3182381535

M. Wynes, L. Sholl, M. Dietel, E. Schuuring, M. Tsao et al., An International Interpretation Study Using the ALK IHC Antibody D5F3 and a Sensitive Detection Kit Demonstrates High Concordance between ALK IHC and ALK FISH and between Evaluators, Journal of Thoracic Oncology, vol.9, issue.5, pp.631-639, 2014.
DOI : 10.1097/JTO.0000000000000115

G. Alì, A. Proietti, S. Pelliccioni, C. Niccoli, C. Lupi et al., Rearrangement in a Large Series of Consecutive Non???Small Cell Lung Cancers: Comparison Between a New Immunohistochemical Approach and Fluorescence In Situ Hybridization for the Screening of Patients Eligible for Crizotinib Treatment, Archives of Pathology & Laboratory Medicine, vol.138, issue.11, pp.1449-58, 2014.
DOI : 10.5858/arpa.2013-0388-OA

M. Mino-kenudson, L. Chirieac, K. Law, J. Hornick, N. Lindeman et al., A Novel, Highly Sensitive Antibody Allows for the Routine Detection of ALK-Rearranged Lung Adenocarcinomas by Standard Immunohistochemistry, Clinical Cancer Research, vol.16, issue.5, pp.1561-71, 2010.
DOI : 10.1158/1078-0432.CCR-09-2845

J. Paik, G. Choe, H. Kim, J. Choe, H. Lee et al., Screening of Anaplastic Lymphoma Kinase Rearrangement by Immunohistochemistry in Non-small Cell Lung Cancer: Correlation with Fluorescence In Situ Hybridization, Journal of Thoracic Oncology, vol.6, issue.3, pp.466-72, 2011.
DOI : 10.1097/JTO.0b013e31820b82e8

L. Jiang, H. Yang, P. He, W. Liang, J. Zhang et al., Improving Selection Criteria for ALK Inhibitor Therapy in Non???Small Cell Lung Cancer, The American Journal of Surgical Pathology, vol.40, issue.5, 2016.
DOI : 10.1097/PAS.0000000000000604

L. Quesne, J. Maurya, M. Yancheva, S. , O. Brien et al., A Comparison of Immunohistochemical Assays and FISH in Detecting the ALK Translocation in Diagnostic Histological and Cytological Lung Tumor Material, Journal of Thoracic Oncology, vol.9, issue.6, pp.769-74, 2014.
DOI : 10.1097/JTO.0000000000000157

C. Conklin, K. Craddock, C. Have, J. Laskin, C. Couture et al., Immunohistochemistry is a Reliable Screening Tool for Identification of ALK Rearrangement in Non???Small-Cell Lung Carcinoma and is Antibody Dependent, Journal of Thoracic Oncology, vol.8, issue.1, pp.45-51, 2013.
DOI : 10.1097/JTO.0b013e318274a83e

M. Von-laffert, A. Stenzinger, M. Hummel, W. Weichert, D. Lenze et al., ALK-FISH borderline cases in non-small cell lung cancer: Implications for diagnostics and clinical decision making. Lung Cancer Amst Neth, 2015.

E. Thunnissen, L. Bubendorf, M. Dietel, G. Elmberger, K. Kerr et al., EML4-ALK testing in non-small cell carcinomas of the lung: a review with recommendations, Virchows Archiv, vol.76, issue.3, pp.245-57, 2012.
DOI : 10.1007/s00428-012-1281-4

X. Gao, L. Sholl, M. Nishino, J. Heng, P. Jänne et al., Clinical Implications of Variant ALK FISH Rearrangement Patterns, Journal of Thoracic Oncology, vol.10, issue.11, pp.1648-52, 2015.
DOI : 10.1097/JTO.0000000000000665

J. Sun, Y. Choi, J. Won, F. Hirsch, J. Ahn et al., A Dramatic Response to Crizotinib in a Non???Small-Cell Lung Cancer Patient with IHC-Positive and FISH-Negative ALK, Journal of Thoracic Oncology, vol.7, issue.12, pp.36-38, 2012.
DOI : 10.1097/JTO.0b013e318274694e

N. Peled, G. Palmer, F. Hirsch, M. Wynes, M. Ilouze et al., Next-Generation Sequencing Identifies and Immunohistochemistry Confirms a Novel Crizotinib-Sensitive ALK Rearrangement in a Patient with Metastatic Non???Small-Cell Lung Cancer, Journal of Thoracic Oncology, vol.7, issue.9, pp.14-16, 2012.
DOI : 10.1097/JTO.0b013e3182614ab5

Y. Cha, J. Lee, H. Kim, S. Lim, B. Cho et al., Screening of ROS1 Rearrangements in Lung Adenocarcinoma by Immunohistochemistry and Comparison with ALK Rearrangements, PLoS ONE, vol.37, issue.7, p.103333, 2014.
DOI : 10.1371/journal.pone.0103333.s002

A. Yoshida, K. Tsuta, S. Wakai, Y. Arai, H. Asamura et al., Immunohistochemical detection of ROS1 is useful for identifying ROS1 rearrangements in lung cancers, Modern Pathology, vol.1795, issue.5, pp.711-731, 2014.
DOI : 10.1371/journal.pone.0015640

A. Platt, J. Morten, J. Q. Elvin, P. Womack, C. Su et al., A retrospective analysis of RET translocation, gene copy number gain and expression in NSCLC patients treated with vandetanib in four randomized Phase III studies, BMC Cancer, vol.31, issue.1, p.171, 2015.
DOI : 10.1097/JTO.0b013e31828a4d07

H. Go, Y. Jung, H. Kang, I. Park, C. Kang et al., Diagnostic method for the detection of KIF5B-RET transformation in lung adenocarcinoma, Lung Cancer, vol.82, issue.1, pp.44-50, 2013.
DOI : 10.1016/j.lungcan.2013.07.009

A. Lamy and J. Sabourin, Les techniques de séquençage « moyen débit » et leurs applications en génétique somatique des tumeurs, Corresp En Onco-Théranostic. mars, vol.3, issue.1, pp.12-20, 2014.

E. Eldering, C. Spek, H. Aberson, A. Grummels, I. Derks et al., Expression profiling via novel multiplex assay allows rapid assessment of gene regulation in defined signalling pathways, Nucleic Acids Research, vol.31, issue.23, p.153, 2003.
DOI : 10.1093/nar/gng153

E. Angot, Evaluation de la RT-DL-PCR multiplexe pour la mise en évidence de transcrits de fusion dans les sarcomes, 2014.

S. Mareschal, P. Ruminy, C. Bagacean, V. Marchand, M. Cornic et al., Accurate Classification of Germinal Center B-Cell???Like/Activated B-Cell???Like Diffuse Large B-Cell Lymphoma Using a Simple and Rapid Reverse Transcriptase???Multiplex Ligation-Dependent Probe Amplification Assay, The Journal of Molecular Diagnostics, vol.17, issue.3, 2015.
DOI : 10.1016/j.jmoldx.2015.01.007

URL : https://hal.archives-ouvertes.fr/hal-01145953

P. Ruminy, V. Marchand, N. Buchbinder, T. Larson, B. Joly et al., Multiplexed targeted sequencing of recurrent fusion genes in acute leukaemia, Leukemia, vol.34, issue.3, 2015.
DOI : 10.1038/ng0996-33

K. Zwaenepoel, D. Merkle, F. Cabillic, E. Berg, M. Belaud-rotureau et al., Automation of ALK gene rearrangement testing with fluorescence in situ hybridization (FISH): A feasibility study, Experimental and Molecular Pathology, vol.98, issue.1, pp.113-121, 2015.
DOI : 10.1016/j.yexmp.2015.01.005

URL : https://hal.archives-ouvertes.fr/hal-01116397

S. Lantuejoul, I. Rouquette, H. Blons, L. Stang, N. Ilie et al., rearrangement diagnostic in 547 lung adenocarcinomas, European Respiratory Journal, vol.46, issue.1, pp.207-225, 2015.
DOI : 10.1183/09031936.00119914