The Unique Characteristics of MET Exon 14 Mutation in Chinese Patients with NSCLC Si-Yang Liu, MD, Lan-Ying Gou, MD, An-Na Li, MD, Na-Na Lou, MMed, Hong-Fei.

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The Unique Characteristics of MET Exon 14 Mutation in Chinese Patients with NSCLC Si-Yang Liu, MD, Lan-Ying Gou, MD, An-Na Li, MD, Na-Na Lou, MMed, Hong-Fei Gao, MD, Jian Su, MMed, Jin-Ji Yang, MD, Xu-Chao Zhang, PhD, Yang Shao, MD, Zhong-Yi Dong, MD, Qing Zhou, PhD, Wen-Zhao Zhong, MD, Yi-Long Wu, MD Journal of Thoracic Oncology Volume 11, Issue 9, Pages 1503-1510 (September 2016) DOI: 10.1016/j.jtho.2016.05.016 Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

Figure 1 Distribution of genotypes among 968 patients receiving next-generation sequencing. FGFR, fibroblast growth factor receptor gene; MET, MNNG HOS Transforming gene; PIK3CA, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha gene; ALK, anaplastic lymphoma receptor tyrosine kinase gene. Journal of Thoracic Oncology 2016 11, 1503-1510DOI: (10.1016/j.jtho.2016.05.016) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

Figure 2 The immunohistochemical (IHC) and fluorescence in situ hybridization (FISH) results for patients with MNNG HOS Transforming gene (MET) exon 14 mutation. del, deletion; NA, not applicable; ORR, objective response rate; PFS, progression-free survival; ADC, adenocarcinoma; SCC, squamous cell carcinoma; ASC, adenosquamous carcinoma. Journal of Thoracic Oncology 2016 11, 1503-1510DOI: (10.1016/j.jtho.2016.05.016) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

Figure 3 Response to crizotinib in a patient with MNNG HOS Transforming gene (MET) exon 14 mutation and concurrent KRAS G12D mutation. A 45-year-old female heavy smoker with a moderately differentiated stage IV adenocarcinoma was found by Sanger sequencing to have (A) a MET exon 14 c.2888_3028 deletion (arrow), (B) moderate mesenchymal-to-transition factor (MET) overexpression (100%++), but no MET amplification (the MET-to–centromere 7 ratio was 1.0) (C). A chest computed tomography scan (axial view) is shown before (D) and after (E) treatment with the cellular mesenchymal-to-epithelial transition factor inhibitor crizotinib (arrow indicates increased tumor in one month). Journal of Thoracic Oncology 2016 11, 1503-1510DOI: (10.1016/j.jtho.2016.05.016) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

Figure 4 Response to crizotinib in a patient with concomitant MNNG HOS Transforming gene (MET) exon 14 mutation and MET amplification. Stage IV lung adenocarcinoma was diagnosed in a 76-year-old male never-smoker. A c.2888_2919 deletion, TCTTTCTCTCTGTTTTAA, was identified by next-generation sequencing in MET exon 14 in 38.4% of 333 reads (A) in association with moderate mesenchymal-to-epithelial transition factor overexpression (80%++) (B) and MET amplification (mean copy number >5.0 per tumor cell (C). A chest computed tomography scan (axial view) is shown before (arrow indicates primary tumor before treatment) (D) and 4 weeks after (E) treatment with the mesenchymal-to-epithelial transition factor inhibitor crizotinib (arrow indicates decreased tumor after treatment). Journal of Thoracic Oncology 2016 11, 1503-1510DOI: (10.1016/j.jtho.2016.05.016) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions