Prevalence and clinical association of gene mutations through multiplex mutation testing in patients with NSCLC: results from the ETOP Lungscape Project.

Détails

ID Serval
serval:BIB_39FAD748912D
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Prevalence and clinical association of gene mutations through multiplex mutation testing in patients with NSCLC: results from the ETOP Lungscape Project.
Périodique
Annals of oncology
Auteur(s)
Kerr K.M., Dafni U., Schulze K., Thunnissen E., Bubendorf L., Hager H., Finn S., Biernat W., Vliegen L., Losa J.H., Marchetti A., Cheney R., Warth A., Speel E.J., Blackhall F., Monkhorst K., Jantus Lewintre E., Tischler V., Clark C., Bertran-Alamillo J., Meldgaard P., Gately K., Wrona A., Vandenberghe P., Felip E., De Luca G., Savic S., Muley T., Smit E.F., Dingemans A.C., Priest L., Baas P., Camps C., Weder W., Polydoropoulou V., Geiger T.R., Kammler R., Sumiyoshi T., Molina M.A., Shames D.S., Stahel R.A., Peters S.
Collaborateur(s)
ETOP Lungscape Consortium
ISSN
1569-8041 (Electronic)
ISSN-L
0923-7534
Statut éditorial
Publié
Date de publication
01/01/2018
Peer-reviewed
Oui
Volume
29
Numéro
1
Pages
200-208
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Reported prevalence of driver gene mutations in non-small-cell lung cancer (NSCLC) is highly variable and clinical correlations are emerging. Using NSCLC biomaterial and clinical data from the European Thoracic Oncology Platform Lungscape iBiobank, we explore the epidemiology of mutations and association to clinicopathologic features and patient outcome (relapse-free survival, time-to-relapse, overall survival).
Clinically annotated, resected stage I-III NSCLC FFPE tissue was assessed for gene mutation using a microfluidics-based multiplex PCR platform. Mutant-allele detection sensitivity is >1% for most of the ∼150 (13 genes) mutations covered in the multiplex test.
Multiplex testing has been carried out in 2063 (76.2%) of the 2709 Lungscape cases (median follow-up 4.8 years). FFPE samples mostly date from 2005 to 2008, yet recently extracted DNA quality and quantity was generally good. Average DNA yield/case was 2.63 µg; 38 cases (1.4%) failed QC and were excluded from study; 95.1% of included cases allowed the complete panel of mutations to be tested. Most common were KRAS, MET, EGFR and PIK3CA mutations with overall prevalence of 23.0%, 6.8%, 5.4% and 4.9%, respectively. KRAS and EGFR mutations were significantly more frequent in adenocarcinomas: PIK3CA in squamous cell carcinomas. MET mutation prevalence did not differ between histology groups. EGFR mutations were found predominantly in never smokers; KRAS in current/former smokers. For all the above mutations, there was no difference in outcome between mutated and non-mutated cases.
Archival FFPE NSCLC material is adequate for multiplex mutation analysis. In this large, predominantly European, clinically annotated stage I-III NSCLC cohort, none of the mutations characterized showed prognostic significance.
Mots-clé
Adult, Aged, Aged, 80 and over, Anaplastic Lymphoma Kinase/biosynthesis, Anaplastic Lymphoma Kinase/genetics, Carcinoma, Non-Small-Cell Lung/epidemiology, Carcinoma, Non-Small-Cell Lung/genetics, Carcinoma, Non-Small-Cell Lung/pathology, DNA Mutational Analysis/methods, Female, Humans, Lung Neoplasms/epidemiology, Lung Neoplasms/genetics, Lung Neoplasms/pathology, Male, Middle Aged, Multiplex Polymerase Chain Reaction/methods, Mutation, Neoplasm Staging, Prevalence, Progression-Free Survival, Proto-Oncogene Proteins c-met/biosynthesis, Proto-Oncogene Proteins c-met/genetics, Smoking/genetics, Young Adult, EGFR, KRAS, PIK3CA, multiplex mutation analysis, non-small-cell lung cancer, prognosis molecular staging
Pubmed
Web of science
Open Access
Oui
Création de la notice
09/12/2017 11:07
Dernière modification de la notice
20/08/2019 14:29
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