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Poster session 01

107P - Systematic characterization of MET activating mutations in non-small cell lung cancer


10 Sep 2022


Poster session 01


Clinical Research;  Targeted Therapy

Tumour Site

Non-Small Cell Lung Cancer


Yao Yu


Annals of Oncology (2022) 33 (suppl_7): S27-S54. 10.1016/annonc/annonc1037


Y. Yu1, Y. Shao2, J. Zhang2, H. Bao2, J. Pang2, R. Guo2, J.C. Yin2, Q. Ou2, X. Wu2

Author affiliations

  • 1 Internal Medicine-oncology, The First Affiliated Hospital of Xi’an Jiaotong University, 710061 - Xi'an/CN
  • 2 Geneseeq Research Institute, Nanjing Geneseeq Technology Inc., 210000 - Nanjing/CN


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Abstract 107P


Alterations in mesenchymal epithelial transition factor (MET) as primary oncogenic drivers or secondary resistance mechanisms to tyrosine kinase inhibitors (TKI) often involve distinct MET mutation subtypes. While MET activating mutations primarily mediates resistance to MET TKIs, increasing evidence suggest that MET activating mutations also exist in the primary tissues. The molecular signatures and clinical relevance of MET activating mutations remain to be elucidated.


We retrospectively reviewed next-generation sequencing data from patients with MET activating mutations (p.H1094, p.L1195, p.Y1230, and p.D1228). Only patients with sufficient clinical data were included. Association analyses of genetic and clinical features were conducted.


Among patients with baseline samples, 24 cases with MET activating mutations were identified, including p.H1094Y/D (45.8%), p.L1195F/V (33.3%), p.D1228N (16.7%), and p.Y1230C (4.2%). A total of 30 MET TKI-treated cases acquired secondary MET activating mutations, including p.D1228N (60.0%), p.D1228H (33.3%), p.Y1230C (10.0%), p.Y1230H (20.0%), p.L1195V (13.3%), p.D1228Y (10.0%), and p.Y1230N (3.3%), which demonstrated significantly different mutational frequencies compared with those of the primary MET activating mutations (P<0.0001). Remarkably, comparing patients with paired baseline and EGFR TKI-treated samples, MET activating mutations, including p.L1195F (36.4%), p.H1094Y (36.4%), p.D1228 (18.2%), and p.D1228N (9.1%) were also detected in 11 post-treatment samples. In addition, the prevalence of different MET activating mutations in the MET TKI- and EGFR TKI-treated cohorts were markedly distinct (P<0.0001). By contrast, no difference was observed in the prevalence of various MET activating mutations at baseline and after EGFR TKI treatment.


Our findings suggest that MET activation might be a spontaneous event in the evolving NSCLC tumor. Selection force imposed by various TKIs may induce subclonal expansion of the pre-existing and/or acquisition of new MET activating mutations. Our findings shed light into the diversity of mechanisms underlying TKI resistance and highlight the potential of sequential use of MET TKI.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.


Has not received any funding.


Y. Shao, J. Zhang, H. Bao, J. Pang, R. Guo, J.C. Yin, Q. Ou, X. Wu: Financial Interests, Personal, Full or part-time Employment: Nanjing Geneseeq Technology Inc. All other authors have declared no conflicts of interest.

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