Background: Mesenchymal-to-epithelial transition (MET) gene mutations, found in 3% of patients with non- small cell lung cancer (NSCLC), have been recognized as a potentially important therapeutic target with the recent approval of MET inhibitor Capmatinib. New technology RNA-Seq has made it possible to directly detect and quantify splice mutation. We set up this study to investigate the clinical significance of this variable RNA expression level of MET with exon 14 splice mutations in patients with NSCLC.

Design: This is a single-center retrospective study of patients with tissue biopsy diagnosed with NSCLC who have undergone genetic tests via RNA-Seq in AdventHealth Orlando from 01/01/2019 and 01/30/2020. Demographic information and clinical data on staging, metastasis, co-existing mutation and treatment were collected. MET14 splice copy number >1000 and MET14/Control gene ratio of 0.05 was used to differentiate between low and high expression.

Results: There were 18 and 17 patients in the low and high expression groups, respectively. The low expression group were notably younger, with history of smoking, higher chance of brain metastasis and harboring lower programmed-death ligand 1 (PD-L1) than its counterpart. All 18 patients within the low expression group were noted to be adenocarcinoma with frequent co-existing gene mutation, as compared with the high expression group with zero co-existing gene mutation. More patients in the high expression group received MET inhibitor treatment.

Conclusions: With the advancements of using RNA-Seq, more MET Exon 14 splicing mutations are able to be detected and quantified. With this new information our data has shown that different RNA levels of expression display different statistical and clinical outcomes. The novelty of this information may be useful when considering the new class of MET 14 exon inhibitors that are available and how they may have different efficacy dependent upon low versus high expressivity.

Table 1