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Purpose  The analysis of  MET  gene copy number (CN) has been considered to be a potential biomarker to predict the response to MET-targeted therapies in various cancers. However, the current standard methods to determine  MET  CN are SNP 6.0 in the genomic DNA of cancer cell lines and fluorescence  in situ  hybridization (FISH) in tumor models, respectively, which are costly and require advanced technical skills and result in relatively subjective judgments. Therefore, we employed a novel method, droplet digital PCR (ddPCR), to determine the  MET  gene copy number with high accuracy and precision.    Methods  The genomic DNA of cancer cell lines or tumor models were tested and compared with the  MET  gene CN and  MET/CEN-7  ratio determined by SNP 6.0 and FISH, respectively.    Results  In cell lines, the linear association of the  MET  CN detected by ddPCR and SNP 6.0 is strong (Pearson correlation = 0.867). In tumor models, the  MET  CN detected by ddPCR was significantly different between the  MET  gene amplification and non-amplification groups according to FISH (mean: 15.4 vs 2.1;  P  = 0.044). Given that  MET  gene amplification is defined as  MET  CN >5.5 by ddPCR, the concordance rate between ddPCR and FISH was 98.0%, and Cohen's kappa coefficient was 0.760 (95% CI, 0.498–1.000;  P  <0.001).    Conclusions  The results demonstrated that the ddPCR method has the potential to quantify the  MET  gene copy number with high precision and accuracy as compared with the results from SNP 6.0 and FISH in cancer cell lines and tumor samples, respectively.

Detection of MET Gene Copy Number in Cancer Samples Using the Droplet Digital PCR Method