Prevalence and clinical association of gene mutations through Multiplex Mutation Testing in patients with NSCLC: Results from the ETOP Lungscape Project

K M Kerr, U Dafni, K Schulze, E Thunnissen, L Bubendorf, H Hager, S Finn, W Biernat, L Vliegen, J H Losa, A Marchetti, R Cheney, A Warth, Ernst-Jan Speel, F Blackhall, K Monkhorst, E Jantus Lewintre, V Tischler, C Clark, J Bertran-AlamilloP Meldgaard, K Gately, A Wrona, P Vandenberghe, E Felip, G De Luca, S Savic, T Muley, E F Smit, A-M C Dingemans, L Priest, P Baas, C Camps, W Weder, V Polydoropoulou, T R Geiger, R Kammler, T Sumiyoshi, M A Molina, D S Shames, R A Stahel, S Peters, ETOP Lungscape Consortium

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: 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 ETOP Lungscape iBiobank, we explore the epidemiology of mutations and association to clinicopathological features and patient outcome (relapse-free survival, time-to-relapse, overall survival).

Methods: 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.

Results: Multiplex testing has been performed in 2063 (76.2%) of the 2709 Lungscape cases (median follow-up 4.8 years). FFPE samples mostly date from 2005-8, yet recently extracted DNA quality and quantity was generally good. Average DNA yield/case was 2.63µg; 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.

Conclusion: 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.

Original languageEnglish
Article numbermdx629
Pages (from-to)200-208
Number of pages9
JournalAnnals of Oncology
Volume29
Issue number1
Early online date23 Nov 2017
DOIs
Publication statusPublished - 1 Jan 2018

Cite this

Kerr, K. M., Dafni, U., Schulze, K., Thunnissen, E., Bubendorf, L., Hager, H., ... ETOP Lungscape Consortium (2018). Prevalence and clinical association of gene mutations through Multiplex Mutation Testing in patients with NSCLC: Results from the ETOP Lungscape Project. Annals of Oncology, 29(1), 200-208. [mdx629]. https://doi.org/10.1093/annonc/mdx629