Abstract 203P
Background
Accumulated evidences have demonstrated that mesenchymal epithelial transition (MET) amplification is one of the main mechanisms of epidermal growth factor receptor–tyrosine kinase inhibitors (EGFR-TKIs) resistance in non-small cell lung cancer (NSCLC). Thus, accurate detection of MET gene copy number (GCN) is essential for the treatment of advanced NSCLC patients resistant to EGFR-TKIs. Herein, we analyzed MET GCN variants including amplification and polysomy in NSCLC patients with resistance to EGFR-TKIs.
Methods
Sixty-nine NSCLC patients resistant to first/second-generation EGFR-TKIs and 63 patients resistant to third-generation EGFR-TKIs were enrolled in this study. MET GCN was detected by FISH using MET and centromere (CEP7) probes in all cases, and by NGS in 38 patients resistant to third-generation EGFR-TKIs.
Results
Compared with NSCLC patients resistant to first/second-generation EGFR-TKIs, both incidences of GCN variants [amplification+polysomy, 11.6% (8/69) vs. 42.9% (27/63), P < 0.001] and amplification [5.8% (4/69) vs. 27.0% (17/63), P = 0.001] were significantly increased in patients resistant to third-generation EGFR-TKIs by FISH. Interestingly, heterogeneity of MET GCN variants, including 7 cases with MET amplification and 1 case with polysomy, was observed only in patients resistant to third-generation EGFR-TKIs, but not in patients resistant to first/second-generation EGFR-TKIs (8/27 vs. 0/8, P = 0.156), although the difference was not statistically significant due to the limited cases. Of 38 cases detected by NGS, 100% (7/7) of patients with FISH homogeneous MET amplification was identified as positivity for MET copy number gain, while only 33.3% (2/6) of heterogeneous amplification and 20.0% (1/5) of polysomy were MET positive.
Conclusions
Higher incidence and heterogeneity of MET GCN variants were demonstrated in NSCLC patients resistant to third-generation EGFR-TKIs than patients resistant to first/second-generation EGFR-TKIs. In technology, FISH showed advantages in detection of MET GCN as compared with NGS. Collectively, these results may provide a guiding role in the accurate detection of MET GCN and subsequent treatments.
Legal entity responsible for the study
The authors.
Funding
Shanghai Rightongene Biotechnology Co., Ltd.
Disclosure
All authors have declared no conflicts of interest.