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MET exon 14 splicing mutation and its correlation with clinocopathological features in subjects with non-small cell lung cancer

Background: Driver mutations are genomic alterations important for tumor initiation and growth. They are found in genes that control cellular proliferation and long-term survival. Mesenchymal-to-epithelial transition (MET) exon 14 splicing mutation occurs in about 3% of cases of non-small cell lung cancer (NSCLC). It has been recognized as an important biomarker to predict response to MET tyrosine-kinase inhibitor therapy. The aim of this study was to investigate possible connection among the MET exon 14 mutations and genomic as well as clinicopathological features in patients with NSCLC. Methods: The study was performed among 270 patients (58% males and 42% females ; mean age of 57.14 ± 16.48 years) with histologically confirmed diagnosis of NSCLC. The distribution of MET exon 14 splicing mutation was detected using the quantitative real-time polymerase chain reaction restriction fragment length polymorphism assay. RNA was extracted from formalin-fixed paraffin-embedded samples. The study was conducted according to the Declaration of Helsinki, the protocol was reviewed and approved by the institutional Ethics committee and all patients provided written informed consent. Results: MET exon 14 splicing mutation was detected in 9 patients (3.4%). It was found in 7 adenocarcinomas (18.9%) and in 2 squamous cell carcinomas (5.4%). Most adenocarcinomas occurred in females and non-smokers. Squamous cell carcinoma predominantly occurred in male smoking patients. All subjects with MET exon 14 splicing mutation had earlier pathology stage of disease (IA, IB, IIA, IIB) (31%) and older age (>75 years) (43%). Overall survival (OS) of these patients were statistically longer than in patients with KRAS and EGFR mutations (2.2 vs. 1.3 months and 2.4 vs. 1.8 months). Conclusions: We found that MET exon 14 splicing mutation occurs at a frequency of 3.4%, in older age, and mostly in early stage of NSCLC. OS of patients harboring MET exon 14 splicing mutation has lasted longer than in patients harboring KRAS and EGFR mutations. Patients with MET exon 14 splicing mutation may respond well to MET tyrosine-kinase inhibitor therapy. Further studies are needed to confirm our results.

MET exon 14 splicing mutation, non-small cell lung cancer

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