Comparative analysis of lung cancer driver mutations from FFPE samples and liquid biopsies by IonTorrent next generation sequencing

Abstract

Introduction: The need for identifying druggable mutations in lung cancer and the difficulties to obtain representative biopsies fostered the use of plasma cell free DNA (cfDNA) as a promising source for detection of tumoral markers. The aim: of this study was to assess the concordance of mutation identified in formalin-fixed paraffin-embedded (FFPE) samples and cfDNA from patients with lung adenocarcinoma by Ion Torrent next generation sequencing. Methods: DNA isolated from both tumor and plasma of seven patients with lung adenocarcinoma was sequenced on an Ion PGM platform using a panel of 50 genes targeting a threshold of 300X minimum coverage for FFPE samples and 1000X for plasma samples.Variant calling was performed with SeqNext software. Results: The mean coverage for libraries of FFPE tissue and plasma samples was 1516X and respectively 3418X. Bioinformatics analysis identified 56 different mutations on 26 genes, out of which 29 different mutations were common to both FFPE tissue and plasma samples. From the commune mutations found in both types of samples 20 mutations were in coding regions containing 13 synonymous mutations and 7 non-synonymous. Globally, the concordance between data obtained from FFPE tissue and plasma samples was 85%. Conclusions: Plasma cell free DNA could be an important sample source for detection of tumoral markers especially when tissue biopsies are difficult to obtain.