{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T23:36:47Z","timestamp":1777246607667,"version":"3.51.4"},"reference-count":50,"publisher":"American Association for Cancer Research (AACR)","issue":"5","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2012,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>We assessed the prognostic and predictive value of \u03b2-tubulin III (TUBB3) expression, as determined by immunohistochemistry, in 412 non\u2013small cell lung cancer (NSCLC) specimens from early-stage patients who received neoadjuvant chemotherapy (paclitaxel- or gemcitabine-based) in a phase III trial (IFCT-0002). We also correlated TUBB3 expression with K-Ras and EGF receptor (EGFR) mutations in a subset of 208 cryopreserved specimens. High TUBB3 protein expression was associated with nonsquamous cell carcinomas (P &amp;lt; 0.001) and K-Ras mutation (P &amp;lt; 0.001). The 127 (30.8%) TUBB3-negative patients derived more than 1 year of overall survival advantage, with more than 84 months median overall survival versus 71.7 months for TUBB3-positive patients [HR, 1.58; 95% confidence interval (CI), 1.11\u20132.25)]. This prognostic value was confirmed in multivariate analysis (adjusted HR for death, 1.51; 95% CI, 1.04\u20132.21; P = 0.031) with a bootstrapping validation procedure. TUBB3 expression was associated with nonresponse to chemotherapy (adjusted HR, 1.31; 95% CI, 1.01\u20131.70; P = 0.044) but had no predictive value (taxane vs. gemcitabine). Taking account of these clinical findings, we further investigated TUBB3 expression in isogenic human bronchial cell lines only differing by K-Ras gene status and assessed the effect of K-Ras short interfering RNA (siRNA) mediated depletion, cell hypoxia, or pharmacologic inhibitors of K-Ras downstream effectors, on TUBB3 protein cell content. siRNA K-Ras knockdown, inhibition of RAF\/MEK (MAP\u2013ERK kinase) and phosphoinositide 3-kinase (PI3K)\/AKT signaling, and hypoxia were shown to downregulate TUBB3 expression in bronchial cells. This study is the first one to identify K-Ras mutations as determinant of TUBB3 expression, a chemoresistance marker. Our in vitro data deserve studies combining standard chemotherapy with anti-MEK or anti-PI3K drugs in patients with TUBB3-overexpressing tumors. Mol Cancer Ther; 11(5); 1203\u201313. \u00a92012 AACR.<\/jats:p>","DOI":"10.1158\/1535-7163.mct-11-0899","type":"journal-article","created":{"date-parts":[[2012,3,13]],"date-time":"2012-03-13T00:35:31Z","timestamp":1331598931000},"page":"1203-1213","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":80,"title":["High TUBB3 Expression, an Independent Prognostic Marker in Patients with Early Non\u2013Small Cell Lung Cancer Treated by Preoperative Chemotherapy, Is Regulated by K-Ras Signaling Pathway"],"prefix":"10.1158","volume":"11","author":[{"given":"Gu\u00e9na\u00eblle","family":"Levallet","sequence":"first","affiliation":[{"name":"Authors' Affiliations:\u20081ER3 INSERM Cancers et Populations, 2Service d'Anatomie Pathologique, 3Service de Pneumologie, 4Unit\u00e9 de Biostatistiques-Recherche Clinique, CHU de Caen; 5UPRES EA2608 USC-INRA Universit\u00e9 de Caen Basse-Normandie, Caen; 6Service d'Anatomie Pathologique, 7Service de Pneumologie, H\u00f4pital Tenon, AP-HP; 8Intergroupe Francophone de Canc\u00e9rologie Thoracique (IFCT), 9U830 INSERM \u201cG\u00e9n\u00e9tique et Biologie des cancers\u201d, Institut Curie, Paris; 10Biochimie et Biologie mol\u00e9culaire, H\u00f4pital de Hautepierre,11Service de Pneumologie, CHRU de Strasbourg, Strasbourg;12UM Biochimie des cancers-Bioth\u00e9rapies, 13INSERM U823, Universit\u00e9 Joseph Fourier, 14P\u00f4le MAC. UF-Oncologie thoracique, CHU de Grenoble, Grenoble;15Service de Pneumologie, CHU de Besan\u00e7on, Besan\u00e7on; 16Service de Pneumologie, CH de Vesoul, Vesoul; 17Service d'Anatomie Pathologique, H\u00f4pital Larrey, CHU de Toulouse, Toulouse; and 18Service de Pneumologie CHU de Montpellier, Montpellier, France"},{"name":"Authors' Affiliations:\u20081ER3 INSERM Cancers et Populations, 2Service d'Anatomie Pathologique, 3Service de Pneumologie, 4Unit\u00e9 de Biostatistiques-Recherche Clinique, CHU de Caen; 5UPRES EA2608 USC-INRA Universit\u00e9 de Caen Basse-Normandie, Caen; 6Service d'Anatomie Pathologique, 7Service de Pneumologie, H\u00f4pital Tenon, AP-HP; 8Intergroupe Francophone de Canc\u00e9rologie Thoracique (IFCT), 9U830 INSERM \u201cG\u00e9n\u00e9tique et Biologie des cancers\u201d, Institut Curie, Paris; 10Biochimie et Biologie mol\u00e9culaire, H\u00f4pital de Hautepierre,11Service de Pneumologie, CHRU de Strasbourg, Strasbourg;12UM Biochimie des cancers-Bioth\u00e9rapies, 13INSERM U823, Universit\u00e9 Joseph Fourier, 14P\u00f4le MAC. UF-Oncologie thoracique, CHU de Grenoble, Grenoble;15Service de Pneumologie, CHU de Besan\u00e7on, Besan\u00e7on; 16Service de Pneumologie, CH de Vesoul, Vesoul; 17Service d'Anatomie Pathologique, H\u00f4pital Larrey, CHU de Toulouse, Toulouse; and 18Service de Pneumologie CHU de Montpellier, Montpellier, France"}]},{"given":"Emmanuel","family":"Bergot","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081ER3 INSERM Cancers et Populations, 2Service d'Anatomie Pathologique, 3Service de Pneumologie, 4Unit\u00e9 de Biostatistiques-Recherche Clinique, CHU de Caen; 5UPRES EA2608 USC-INRA Universit\u00e9 de Caen Basse-Normandie, Caen; 6Service d'Anatomie Pathologique, 7Service de Pneumologie, H\u00f4pital Tenon, AP-HP; 8Intergroupe Francophone de Canc\u00e9rologie Thoracique (IFCT), 9U830 INSERM \u201cG\u00e9n\u00e9tique et Biologie des cancers\u201d, Institut Curie, Paris; 10Biochimie et Biologie mol\u00e9culaire, H\u00f4pital de Hautepierre,11Service de Pneumologie, CHRU de Strasbourg, Strasbourg;12UM Biochimie des cancers-Bioth\u00e9rapies, 13INSERM U823, Universit\u00e9 Joseph Fourier, 14P\u00f4le MAC. UF-Oncologie thoracique, CHU de Grenoble, Grenoble;15Service de Pneumologie, CHU de Besan\u00e7on, Besan\u00e7on; 16Service de Pneumologie, CH de Vesoul, Vesoul; 17Service d'Anatomie Pathologique, H\u00f4pital Larrey, CHU de Toulouse, Toulouse; and 18Service de Pneumologie CHU de Montpellier, Montpellier, France"},{"name":"Authors' Affiliations:\u20081ER3 INSERM Cancers et Populations, 2Service d'Anatomie Pathologique, 3Service de Pneumologie, 4Unit\u00e9 de Biostatistiques-Recherche Clinique, CHU de Caen; 5UPRES EA2608 USC-INRA Universit\u00e9 de Caen Basse-Normandie, Caen; 6Service d'Anatomie Pathologique, 7Service de Pneumologie, H\u00f4pital Tenon, AP-HP; 8Intergroupe Francophone de Canc\u00e9rologie Thoracique (IFCT), 9U830 INSERM \u201cG\u00e9n\u00e9tique et Biologie des cancers\u201d, Institut Curie, Paris; 10Biochimie et Biologie mol\u00e9culaire, H\u00f4pital de Hautepierre,11Service de Pneumologie, CHRU de Strasbourg, Strasbourg;12UM Biochimie des cancers-Bioth\u00e9rapies, 13INSERM U823, Universit\u00e9 Joseph Fourier, 14P\u00f4le MAC. UF-Oncologie thoracique, CHU de Grenoble, Grenoble;15Service de Pneumologie, CHU de Besan\u00e7on, Besan\u00e7on; 16Service de Pneumologie, CH de Vesoul, Vesoul; 17Service d'Anatomie Pathologique, H\u00f4pital Larrey, CHU de Toulouse, Toulouse; and 18Service de Pneumologie CHU de Montpellier, Montpellier, France"}]},{"given":"Martine","family":"Antoine","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081ER3 INSERM Cancers et Populations, 2Service d'Anatomie Pathologique, 3Service de Pneumologie, 4Unit\u00e9 de Biostatistiques-Recherche Clinique, CHU de Caen; 5UPRES EA2608 USC-INRA Universit\u00e9 de Caen Basse-Normandie, Caen; 6Service d'Anatomie Pathologique, 7Service de Pneumologie, H\u00f4pital Tenon, AP-HP; 8Intergroupe Francophone de Canc\u00e9rologie Thoracique (IFCT), 9U830 INSERM \u201cG\u00e9n\u00e9tique et Biologie des cancers\u201d, Institut Curie, Paris; 10Biochimie et Biologie mol\u00e9culaire, H\u00f4pital de Hautepierre,11Service de Pneumologie, CHRU de Strasbourg, Strasbourg;12UM Biochimie des cancers-Bioth\u00e9rapies, 13INSERM U823, Universit\u00e9 Joseph Fourier, 14P\u00f4le MAC. UF-Oncologie thoracique, CHU de Grenoble, Grenoble;15Service de Pneumologie, CHU de Besan\u00e7on, Besan\u00e7on; 16Service de Pneumologie, CH de Vesoul, Vesoul; 17Service d'Anatomie Pathologique, H\u00f4pital Larrey, CHU de Toulouse, Toulouse; and 18Service de Pneumologie CHU de Montpellier, Montpellier, France"}]},{"given":"Christian","family":"Creveuil","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081ER3 INSERM Cancers et Populations, 2Service d'Anatomie Pathologique, 3Service de Pneumologie, 4Unit\u00e9 de Biostatistiques-Recherche Clinique, CHU de Caen; 5UPRES EA2608 USC-INRA Universit\u00e9 de Caen Basse-Normandie, Caen; 6Service d'Anatomie Pathologique, 7Service de Pneumologie, H\u00f4pital Tenon, AP-HP; 8Intergroupe Francophone de Canc\u00e9rologie Thoracique (IFCT), 9U830 INSERM \u201cG\u00e9n\u00e9tique et Biologie des cancers\u201d, Institut Curie, Paris; 10Biochimie et Biologie mol\u00e9culaire, H\u00f4pital de Hautepierre,11Service de Pneumologie, CHRU de Strasbourg, Strasbourg;12UM Biochimie des cancers-Bioth\u00e9rapies, 13INSERM U823, Universit\u00e9 Joseph Fourier, 14P\u00f4le MAC. UF-Oncologie thoracique, CHU de Grenoble, Grenoble;15Service de Pneumologie, CHU de Besan\u00e7on, Besan\u00e7on; 16Service de Pneumologie, CH de Vesoul, Vesoul; 17Service d'Anatomie Pathologique, H\u00f4pital Larrey, CHU de Toulouse, Toulouse; and 18Service de Pneumologie CHU de Montpellier, Montpellier, France"}]},{"given":"Adriana O.","family":"Santos","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081ER3 INSERM Cancers et Populations, 2Service d'Anatomie Pathologique, 3Service de Pneumologie, 4Unit\u00e9 de Biostatistiques-Recherche Clinique, CHU de Caen; 5UPRES EA2608 USC-INRA Universit\u00e9 de Caen Basse-Normandie, Caen; 6Service d'Anatomie Pathologique, 7Service de Pneumologie, H\u00f4pital Tenon, AP-HP; 8Intergroupe Francophone de Canc\u00e9rologie Thoracique (IFCT), 9U830 INSERM \u201cG\u00e9n\u00e9tique et Biologie des cancers\u201d, Institut Curie, Paris; 10Biochimie et Biologie mol\u00e9culaire, H\u00f4pital de Hautepierre,11Service de Pneumologie, CHRU de Strasbourg, Strasbourg;12UM Biochimie des cancers-Bioth\u00e9rapies, 13INSERM U823, Universit\u00e9 Joseph Fourier, 14P\u00f4le MAC. UF-Oncologie thoracique, CHU de Grenoble, Grenoble;15Service de Pneumologie, CHU de Besan\u00e7on, Besan\u00e7on; 16Service de Pneumologie, CH de Vesoul, Vesoul; 17Service d'Anatomie Pathologique, H\u00f4pital Larrey, CHU de Toulouse, Toulouse; and 18Service de Pneumologie CHU de Montpellier, Montpellier, France"}]},{"given":"Michelle","family":"Beau-Faller","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081ER3 INSERM Cancers et Populations, 2Service d'Anatomie Pathologique, 3Service de Pneumologie, 4Unit\u00e9 de Biostatistiques-Recherche Clinique, CHU de Caen; 5UPRES EA2608 USC-INRA Universit\u00e9 de Caen Basse-Normandie, Caen; 6Service d'Anatomie Pathologique, 7Service de Pneumologie, H\u00f4pital Tenon, AP-HP; 8Intergroupe Francophone de Canc\u00e9rologie Thoracique (IFCT), 9U830 INSERM \u201cG\u00e9n\u00e9tique et Biologie des cancers\u201d, Institut Curie, Paris; 10Biochimie et Biologie mol\u00e9culaire, H\u00f4pital de Hautepierre,11Service de Pneumologie, CHRU de Strasbourg, Strasbourg;12UM Biochimie des cancers-Bioth\u00e9rapies, 13INSERM U823, Universit\u00e9 Joseph Fourier, 14P\u00f4le MAC. UF-Oncologie thoracique, CHU de Grenoble, Grenoble;15Service de Pneumologie, CHU de Besan\u00e7on, Besan\u00e7on; 16Service de Pneumologie, CH de Vesoul, Vesoul; 17Service d'Anatomie Pathologique, H\u00f4pital Larrey, CHU de Toulouse, Toulouse; and 18Service de Pneumologie CHU de Montpellier, Montpellier, France"}]},{"given":"Florence","family":"de Fraipont","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081ER3 INSERM Cancers et Populations, 2Service d'Anatomie Pathologique, 3Service de Pneumologie, 4Unit\u00e9 de Biostatistiques-Recherche Clinique, CHU de Caen; 5UPRES EA2608 USC-INRA Universit\u00e9 de Caen Basse-Normandie, Caen; 6Service d'Anatomie Pathologique, 7Service de Pneumologie, H\u00f4pital Tenon, AP-HP; 8Intergroupe Francophone de Canc\u00e9rologie Thoracique (IFCT), 9U830 INSERM \u201cG\u00e9n\u00e9tique et Biologie des cancers\u201d, Institut Curie, Paris; 10Biochimie et Biologie mol\u00e9culaire, H\u00f4pital de Hautepierre,11Service de Pneumologie, CHRU de Strasbourg, Strasbourg;12UM Biochimie des cancers-Bioth\u00e9rapies, 13INSERM U823, Universit\u00e9 Joseph Fourier, 14P\u00f4le MAC. UF-Oncologie thoracique, CHU de Grenoble, Grenoble;15Service de Pneumologie, CHU de Besan\u00e7on, Besan\u00e7on; 16Service de Pneumologie, CH de Vesoul, Vesoul; 17Service d'Anatomie Pathologique, H\u00f4pital Larrey, CHU de Toulouse, Toulouse; and 18Service de Pneumologie CHU de Montpellier, Montpellier, France"}]},{"given":"Elisabeth","family":"Brambilla","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081ER3 INSERM Cancers et Populations, 2Service d'Anatomie Pathologique, 3Service de Pneumologie, 4Unit\u00e9 de Biostatistiques-Recherche Clinique, CHU de Caen; 5UPRES EA2608 USC-INRA Universit\u00e9 de Caen Basse-Normandie, Caen; 6Service d'Anatomie Pathologique, 7Service de Pneumologie, H\u00f4pital Tenon, AP-HP; 8Intergroupe Francophone de Canc\u00e9rologie Thoracique (IFCT), 9U830 INSERM \u201cG\u00e9n\u00e9tique et Biologie des cancers\u201d, Institut Curie, Paris; 10Biochimie et Biologie mol\u00e9culaire, H\u00f4pital de Hautepierre,11Service de Pneumologie, CHRU de Strasbourg, Strasbourg;12UM Biochimie des cancers-Bioth\u00e9rapies, 13INSERM U823, Universit\u00e9 Joseph Fourier, 14P\u00f4le MAC. UF-Oncologie thoracique, CHU de Grenoble, Grenoble;15Service de Pneumologie, CHU de Besan\u00e7on, Besan\u00e7on; 16Service de Pneumologie, CH de Vesoul, Vesoul; 17Service d'Anatomie Pathologique, H\u00f4pital Larrey, CHU de Toulouse, Toulouse; and 18Service de Pneumologie CHU de Montpellier, Montpellier, France"}]},{"given":"J\u00e9r\u00f4me","family":"Levallet","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081ER3 INSERM Cancers et Populations, 2Service d'Anatomie Pathologique, 3Service de Pneumologie, 4Unit\u00e9 de Biostatistiques-Recherche Clinique, CHU de Caen; 5UPRES EA2608 USC-INRA Universit\u00e9 de Caen Basse-Normandie, Caen; 6Service d'Anatomie Pathologique, 7Service de Pneumologie, H\u00f4pital Tenon, AP-HP; 8Intergroupe Francophone de Canc\u00e9rologie Thoracique (IFCT), 9U830 INSERM \u201cG\u00e9n\u00e9tique et Biologie des cancers\u201d, Institut Curie, Paris; 10Biochimie et Biologie mol\u00e9culaire, H\u00f4pital de Hautepierre,11Service de Pneumologie, CHRU de Strasbourg, Strasbourg;12UM Biochimie des cancers-Bioth\u00e9rapies, 13INSERM U823, Universit\u00e9 Joseph Fourier, 14P\u00f4le MAC. UF-Oncologie thoracique, CHU de Grenoble, Grenoble;15Service de Pneumologie, CHU de Besan\u00e7on, Besan\u00e7on; 16Service de Pneumologie, CH de Vesoul, Vesoul; 17Service d'Anatomie Pathologique, H\u00f4pital Larrey, CHU de Toulouse, Toulouse; and 18Service de Pneumologie CHU de Montpellier, Montpellier, France"}]},{"given":"Franck","family":"Morin","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081ER3 INSERM Cancers et Populations, 2Service d'Anatomie Pathologique, 3Service de Pneumologie, 4Unit\u00e9 de Biostatistiques-Recherche Clinique, CHU de Caen; 5UPRES EA2608 USC-INRA Universit\u00e9 de Caen Basse-Normandie, Caen; 6Service d'Anatomie Pathologique, 7Service de Pneumologie, H\u00f4pital Tenon, AP-HP; 8Intergroupe Francophone de Canc\u00e9rologie Thoracique (IFCT), 9U830 INSERM \u201cG\u00e9n\u00e9tique et Biologie des cancers\u201d, Institut Curie, Paris; 10Biochimie et Biologie mol\u00e9culaire, H\u00f4pital de Hautepierre,11Service de Pneumologie, CHRU de Strasbourg, Strasbourg;12UM Biochimie des cancers-Bioth\u00e9rapies, 13INSERM U823, Universit\u00e9 Joseph Fourier, 14P\u00f4le MAC. UF-Oncologie thoracique, CHU de Grenoble, Grenoble;15Service de Pneumologie, CHU de Besan\u00e7on, Besan\u00e7on; 16Service de Pneumologie, CH de Vesoul, Vesoul; 17Service d'Anatomie Pathologique, H\u00f4pital Larrey, CHU de Toulouse, Toulouse; and 18Service de Pneumologie CHU de Montpellier, Montpellier, France"}]},{"given":"Virginie","family":"Westeel","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081ER3 INSERM Cancers et Populations, 2Service d'Anatomie Pathologique, 3Service de Pneumologie, 4Unit\u00e9 de Biostatistiques-Recherche Clinique, CHU de Caen; 5UPRES EA2608 USC-INRA Universit\u00e9 de Caen Basse-Normandie, Caen; 6Service d'Anatomie Pathologique, 7Service de Pneumologie, H\u00f4pital Tenon, AP-HP; 8Intergroupe Francophone de Canc\u00e9rologie Thoracique (IFCT), 9U830 INSERM \u201cG\u00e9n\u00e9tique et Biologie des cancers\u201d, Institut Curie, Paris; 10Biochimie et Biologie mol\u00e9culaire, H\u00f4pital de Hautepierre,11Service de Pneumologie, CHRU de Strasbourg, Strasbourg;12UM Biochimie des cancers-Bioth\u00e9rapies, 13INSERM U823, Universit\u00e9 Joseph Fourier, 14P\u00f4le MAC. UF-Oncologie thoracique, CHU de Grenoble, Grenoble;15Service de Pneumologie, CHU de Besan\u00e7on, Besan\u00e7on; 16Service de Pneumologie, CH de Vesoul, Vesoul; 17Service d'Anatomie Pathologique, H\u00f4pital Larrey, CHU de Toulouse, Toulouse; and 18Service de Pneumologie CHU de Montpellier, Montpellier, France"}]},{"given":"Marie","family":"Wislez","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081ER3 INSERM Cancers et Populations, 2Service d'Anatomie Pathologique, 3Service de Pneumologie, 4Unit\u00e9 de Biostatistiques-Recherche Clinique, CHU de Caen; 5UPRES EA2608 USC-INRA Universit\u00e9 de Caen Basse-Normandie, Caen; 6Service d'Anatomie Pathologique, 7Service de Pneumologie, H\u00f4pital Tenon, AP-HP; 8Intergroupe Francophone de Canc\u00e9rologie Thoracique (IFCT), 9U830 INSERM \u201cG\u00e9n\u00e9tique et Biologie des cancers\u201d, Institut Curie, Paris; 10Biochimie et Biologie mol\u00e9culaire, H\u00f4pital de Hautepierre,11Service de Pneumologie, CHRU de Strasbourg, Strasbourg;12UM Biochimie des cancers-Bioth\u00e9rapies, 13INSERM U823, Universit\u00e9 Joseph Fourier, 14P\u00f4le MAC. UF-Oncologie thoracique, CHU de Grenoble, Grenoble;15Service de Pneumologie, CHU de Besan\u00e7on, Besan\u00e7on; 16Service de Pneumologie, CH de Vesoul, Vesoul; 17Service d'Anatomie Pathologique, H\u00f4pital Larrey, CHU de Toulouse, Toulouse; and 18Service de Pneumologie CHU de Montpellier, Montpellier, France"}]},{"given":"Elisabeth","family":"Quoix","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081ER3 INSERM Cancers et Populations, 2Service d'Anatomie Pathologique, 3Service de Pneumologie, 4Unit\u00e9 de Biostatistiques-Recherche Clinique, CHU de Caen; 5UPRES EA2608 USC-INRA Universit\u00e9 de Caen Basse-Normandie, Caen; 6Service d'Anatomie Pathologique, 7Service de Pneumologie, H\u00f4pital Tenon, AP-HP; 8Intergroupe Francophone de Canc\u00e9rologie Thoracique (IFCT), 9U830 INSERM \u201cG\u00e9n\u00e9tique et Biologie des cancers\u201d, Institut Curie, Paris; 10Biochimie et Biologie mol\u00e9culaire, H\u00f4pital de Hautepierre,11Service de Pneumologie, CHRU de Strasbourg, Strasbourg;12UM Biochimie des cancers-Bioth\u00e9rapies, 13INSERM U823, Universit\u00e9 Joseph Fourier, 14P\u00f4le MAC. 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