دورية أكاديمية

Clinical Relevance of EGFR - or KRAS - mutated Subclones in Patients With Advanced Non–small-cell Lung Cancer Receiving Erlotinib in a French Prospective Cohort (IFCT ERMETIC2 Cohort - Part 2)

التفاصيل البيبلوغرافية
العنوان: Clinical Relevance of EGFR - or KRAS - mutated Subclones in Patients With Advanced Non–small-cell Lung Cancer Receiving Erlotinib in a French Prospective Cohort (IFCT ERMETIC2 Cohort - Part 2)
المؤلفون: Beau-Faller, Michèle, Texier, Matthieu, Blons, Hélène, Richard, Nicolas, Escande, Fabienne, Melaabi, Samia, Lizard, Sarab, De Fraipont, Florence, Longchampt, Elisabeth, Morin, Franck, Zalcman, Gérard, Pignon, Jean-Pierre, Cadranel, Jacques
المساهمون: Laboratoire de Biochimie et de Biologie Moléculaire, CHU Strasbourg-Hôpital de Hautepierre Strasbourg, Embedded Computing Laboratory Gif-sur-Yvette, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique Gustave Roussy, Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Université Paris Descartes - Paris 5 (UPD5), Biologie, génétique et thérapies ostéoarticulaires et respiratoires (BIOTARGEN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Service de Génétique CHU Caen, Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), biology and pathological laboratory, Unit of Pharmacogenomics, Department of Genetics, Institut Curie Paris, Département de Biologie et pathologie des tumeurs Centre Georges-François Leclerc, Centre Régional de Lutte contre le cancer Georges-François Leclerc Dijon (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, INSERM U823, équipe 5 (cibles diagnostiques ou thérapeutiques et vectorisation de drogues dans le cancer du poumon), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)-UM Biochimie des Cancers et Biothérapies, CHU Grenoble-Institut de Biologie et Pathologie-Institut de Biologie et Pathologie, Hôpital Foch Suresnes, Amplitude Systèmes, Service de Pneumologie, Hôpital Côte de Nacre CHU Caen, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Theranoscan, Université Pierre et Marie Curie - Paris 6 (UPMC)
المصدر: ISSN: 1525-7304 ; Clinical Lung Cancer ; https://hal-normandie-univ.archives-ouvertes.fr/hal-02267702Test ; Clinical Lung Cancer, Elsevier, 2019, 20 (3), pp.222-230. ⟨10.1016/j.cllc.2018.12.012⟩.
بيانات النشر: HAL CCSD
Elsevier
سنة النشر: 2019
المجموعة: Archive ouverte HAL (Hyper Article en Ligne, CCSD - Centre pour la Communication Scientifique Directe)
مصطلحات موضوعية: Sensitivity, Tyrosine kinase inhibitor, NSCLC, Molecular techniques, Driver mutations, [SDV.CAN]Life Sciences [q-bio]/Cancer
الوصف: International audience ; IntroductionEvaluation of EGFR Mutation status for the administration of EGFR-TKIs in non-small cell lung Carcinoma (ERMETIC) was a prospective study designed to validate the prognostic value of EGFR/KRAS mutations in patients with advanced non–small-cell lung cancer (NSCLC), all receiving a first-generation tyrosine kinase inhibitor, erlotinib. ERMETIC2 was an ancillary project evaluating the clinical value of common EGFR/KRAS-mutated subclones regarding prognosis using highly sensitive molecular detection methods.Materials and MethodsTumor samples from 228 patients with NSCLC (59% adenocarcinoma, 37% women, and 19% never/former smokers) were available for reanalysis using alternative highly sensitive molecular techniques. A multivariate Cox model was used for prognostic analysis.ResultsUsing alternative highly sensitive techniques, 16 EGFR and 51 KRAS supplementary mutations were newly identified, all still exclusive, leading to an overall rate of 12.3% (n = 28) and 33.3% (n = 76), respectively. Using real-time polymerase chain reaction (hybridization probe), they were significantly associated with progression-free survival (P = .02) and overall survival (OS) (P = .01), which were better for EGFR-mutated patients for progression-free survival (hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.28-0.78) and OS (HR, 0.56; 95% CI, 0.31-1), and worse for KRAS mutations and OS (HR, 1.63; 95% CI, 1.09-2.44). Using the most sensitive technique detection for KRAS–clamp polymerase chain reaction–KRAS mutated subclones did not impact OS.ConclusionsKRAS and EGFR mutations were detected in higher proportions by alternative highly sensitive molecular techniques compared with direct Sanger sequencing. However, minor KRAS-mutated subclones offered no prognostic value when representing less than 1% of the tumor cells.
نوع الوثيقة: article in journal/newspaper
اللغة: English
العلاقة: hal-02267702; https://hal-normandie-univ.archives-ouvertes.fr/hal-02267702Test; https://hal-normandie-univ.archives-ouvertes.fr/hal-02267702/documentTest; https://hal-normandie-univ.archives-ouvertes.fr/hal-02267702/file/S152573041830336X.pdfTest; PII: S1525-7304(18)30336-X
DOI: 10.1016/j.cllc.2018.12.012
الإتاحة: https://doi.org/10.1016/j.cllc.2018.12.012Test
https://hal-normandie-univ.archives-ouvertes.fr/hal-02267702Test
https://hal-normandie-univ.archives-ouvertes.fr/hal-02267702/documentTest
https://hal-normandie-univ.archives-ouvertes.fr/hal-02267702/file/S152573041830336X.pdfTest
حقوق: http://creativecommons.org/licenses/by-ncTest/ ; info:eu-repo/semantics/OpenAccess
رقم الانضمام: edsbas.8E8E21D6
قاعدة البيانات: BASE