MET Amplification in Non-Small Cell Lung Cancer (NSCLC)—A Consecutive Evaluation Using Next-Generation Sequencing (NGS) in a Real-World Setting

Abstract

In non-small cell lung cancer (NSCLC), approximately 1-3% of cases harbor an increased gene copy number (GCN) of the <i>MET</i> gene. This alteration can be due to de novo amplification of the <i>MET</i> gene or can represent a secondary resistance mechanism in response to targeted therapies. To date, the gold standard method to evaluate the GCN of <i>MET</i> is fluorescence in situ hybridization (FISH). However, next-generation sequencing (NGS) is becoming more relevant to optimize therapy by revealing the mutational profile of each NSCLC. Using evaluable <i>n</i> = 205 NSCLC cases of a consecutive cohort, this study addressed the question of whether an amplicon based NGS assay can completely replace the FISH method regarding the classification of <i>MET</i> GCN status. Out of the 205 evaluable cases, only <i>n</i> = 9 cases (43.7%) of <i>n</i> = 16 high-level <i>MET</i> amplified cases assessed by FISH were classified as amplified by NGS. Cases harboring a <i>MET</i> GCN > 10 showed the best concordance when comparing FISH versus NGS (80%). This study confirms that an amplicon-based NGS assessment of the <i>MET</i> GCN detects high-level <i>MET</i> amplified cases harboring a <i>MET</i> GCN > 10 but fails to detect the various facets of <i>MET</i> gene amplification in the context of a therapy-induced resistance mechanism.