e14543 Background: Somatic mutations in MET are diverse and include MET amplification, exon 14 skipping and also some functional point mutations (H1094Y, Y1230H, D1228N, etc). Generally, amplification and ex14 skipping are the two main mutation types. Methods: MET mutation profiles were analyzed using hybridization capture based next-generation sequencing (NGS), which enables the simultaneous detection of multi-mutation types of at least 59 genes (range 59-1021 genes). Results: Screening tens of thousands treatment naive patients, we found 319 patients with MET mutations, 56 patients (18%) with MET amplification, 55 patients (17%) with MET ex14 skipping, and 214 patients with other unknown functional point mutations. 39 cases with MET amplification and 52 cases with MET ex14 skipping in lung cancer. Patients with MET amplification or ex14 skipping had fewer mutations compared with patients with other MET mutations ( P < 0.0001), while there were no differences in ctDNA abundance between two groups ( P = 0.58). Further compared the MET amplification and ex14 skipping groups, we found mutation numbers and ctDNA abundance were both significant lower in ex14 skipping group (mutation numbers: P = 0.0134; ctDNA abundance: P < 0.0001). MET amplification range from 2 to 7 copies in these 39 patients, and patients with more than 3 copies had a higher ctDNA abundance than = < 3 copies patients ( P < 0.0005). Six patients with both amplification and ex 14 skipping, all of them with advanced age ( > 70 years). Of the MET amplification group, 11 patients (28%) developed EGFR driver mutation concurrently, four patients with L858R, three with ex19 del, one with G719A, one with both L858R and EGFR amplification, one with both ex19 del and amplification and one with only amplification, while no patients were found to have any EGFR driver mutation in MET ex14 skipping group. Conclusions: The cfDNA from patients with EGFR amplification or ex14 skipping was only 18% or 17% in MET mutations. Both of these two mutation types were mainly found in lung cancer. Furthermore, MET amplification group patients had fewer mutations and lower ctDNA abundance. In treatment naïve patients, MET amplification concurrent with other EGFR drive mutations, rather than ex14 skipping.
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