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)
| 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, Centre Hospitalier Universitaire Strasbourg (CHU Strasbourg), Les Hôpitaux Universitaires de Strasbourg (HUS)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Hôpital de Hautepierre Strasbourg, Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique Gustave Roussy, Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Département d'Architectures, Conception et Logiciels Embarqués-LIST (DACLE-LIST), Laboratoire d'Intégration des Systèmes et des Technologies (LIST (CEA)), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), 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, Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-Centre Hospitalier Universitaire CHU Grenoble (CHUGA)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Theranoscan, Université Pierre et Marie Curie - Paris 6 (UPMC) |
| المصدر: | ISSN: 1525-7304. |
| بيانات النشر: | HAL CCSD Elsevier |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Driver mutations, Molecular techniques, NSCLC, Tyrosine kinase inhibitor, Sensitivity, [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://normandie-univ.hal.science/hal-02267702Test; https://normandie-univ.hal.science/hal-02267702/documentTest; https://normandie-univ.hal.science/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://normandie-univ.hal.science/hal-02267702Test https://normandie-univ.hal.science/hal-02267702/documentTest https://normandie-univ.hal.science/hal-02267702/file/S152573041830336X.pdfTest |
| حقوق: | http://creativecommons.org/licenses/by-ncTest/ ; info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.5FFC8694 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.cllc.2018.12.012 |
|---|