Response to Crizotinib Observed in Lung Adenocarcinoma with MET Copy Number Gain but without a High-Level MET/CEP7 Ratio, MET Overexpression, or Exon 14 Splicing Mutations

Abstract

MMNG HOS Transforming gene (MET) is an important driver gene in non-small cell lung cancer. Yet, MET-relevant biomarkers predictive of clinical response to MET inhibitors remain elusive. Limited studies have indicated some possibly effective biomarkers, including amplification with a high-level MET/centromere probe of chromosome 7 (CEP7) ratio, MET exon 14 (METex14) splicing mutations, and MET overexpression. MET copy number gain (MCNG) is an independent negative prognostic factor in non-small cell lung cancer. Therefore, there remains a lack of clinical evidence regarding whether MCNG is a biomarker predictive of response to MET inhibitors. Here we report a patient with lung adenocarcinoma with MCNG but without a high-level MET/CEP7 ratio or METex14 splicing mutations who achieved a rapid response to crizotinib, indicating that MCNG may be an independent predictive biomarker for response to MET inhibitors.

Keywords: Copy number gain; Crizotinib; Lung cancer; MET/CEP7 ratio; Mesenchymal-epithelial transition.