Clinical and molecular Characterization of NSCLCs with MET exon 14 skipping mutation coexist MET amplification.

Abstract

e20506 Background: MET exon 14 skipping mutation (METex14) and MET amplification are the most prevalent molecular alterations associated with MET carcinogenesis in non-small cell lung cancer, with respective frequencies of 3-4% and 1-5%. Recent research indicates that patients with METex14 may also carry MET amplification, and that MET-TKI therapy has a higher response rate in this patient population. We evaluated the clinical and molecular characteristics of patients with altered or co-altered MET using NGS data of non-small cell lung cancer cases from Jiangsu Simcere diagnostic Co., ltd. Methods: During 2019-2021, samples from 33074 NSCLC patients underwent comprehensive genomic profiling (CGP) using hybrid-capture technology at the Simcere diagnostic laboratory (Nanjing, China). To detect gene mutations in tumor tissue or blood samples of patients, next-generation sequencing (NGS) was performed. MET amplification was defined as MET copy number greater than 2.25. Results: MET exon 14 skipping was found in 325 pts (0.98%), MET amplification was found in 136 pts (0.41%), and the co-alter population consisted of only 36 pts (0.11%). Receptor, Donor, D1010, Y1003, and other METex14 subtypes represented 12.0%, 36.6%, 24.6%, 0.2%, and 26.2%, respectively, of the population. Then, we divided MET-altered NSCLC patients into three groups: MET14 (carrying only METex14), AMP (carrying only MET amplification), and MET14&AMP (MET14 concomitant MET amplification). The differences in age, gender, TMB copy number, and MET copy number were then compared between these groups. Patients with AMP were considerably younger than those with METex14&AMP or AMP. (MET14&AMP: 69.0±9.27 vs AMP: 63.5±10.6, P = 0.032; MET14: 70.0±10.9, P < 0.001). The AMP group contained significantly more male patients than the MET14 group (68.0% vs. 54.5%, P = 0.019), but there were no significant differences between the remaining groups. In contrast to tissue-based TMB, the AMP group was significantly higher than the other two (AMP:17.059.5 vs MET 14: 2.945.79; P0.001; MET14&AMP: 3.650.63, P = 0.005). In spite of this, there was no statistically significant difference between the AMP and MET14 & AMP groups in terms of MET copy number or percentage of MET CN > = 10. Conclusions: In general, AMP pts are younger and have a higher TMB than co-alteration pts; however, there is no significant difference in MET CN between AMP and co-alteration pts; whether the coexisting group is sensitive to MET-TKI is unknown, and future research should focus on the treatment of co-alteration and AMP pts.