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Background   MET  amplification plays an important role in the development of non-small-cell lung cancer (NSCLC) either de novo or in resistance to epidermal growth factor receptor tyrosine–kinase inhibitor (EGFR-TKI) settings. Fluorescence in situ hybridization (FISH) is the standard method for  MET  amplification. With more and more discoveries of oncogenic driver genes, next-generation sequencing (NGS) plays a significant role in precision oncology. Meanwhile, the role of NGS in  MET  amplification remains uncertain.    Methods  Forty patients diagnosed with advanced NSCLC were included. FISH and NGS were conducted prior to MET inhibitors treatment.  MET  amplification by FISH was defined as a MET/CEP7 ratio of  >  2.0 and/or copy number (CN)  >  5.  MET  amplification by NGS was defined as gene copy number (GCN)  ≥  5.    Results  The concordance rate among FISH and NGS was 62.5% (25/40).  MET  amplification identified by FISH showed the optimal predictive value. The partial response (PR) rate was 68.0% (17/25 with  MET  amplification) vs. 6.7% (1/15 without  MET  amplification); the median progression-free survival (PFS) was 5.4 months versus 1.0 months (P  < 0.001).  MET  amplification identified by NGS failed to distinguish significant clinical outcomes. The PR rate was 60.0% (6/10, with  MET  GCN  ≥ 5) vs. 40.0% (12/30, with  MET  GCN  < 5); the median PFS was 4.8 months vs. 2.2 months (P  = 0.357). The PR rate was 68.8% (11/16) and the median PFS was 4.8 months in patients with focal amplification by NGS.    Conclusions   MET  amplification identified by FISH remains the optimal biomarker to identify suitable candidates for MET-TKI therapy. In comparison, amplification identified by NGS seems not as robust to be effective predictive biomarker. Further exploration is needed regarding the focal amplification by NGS in predicting the efficacy.    Supplementary Information  The online version contains supplementary material available at 10.1186/s40164-021-00245-y.

MET amplification identified by next-generation sequencing and its clinical relevance for MET inhibitors