Alexa B. Schrock, PhD, Garrett M

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Comprehensive genomic profiling of 298 lung cancers of varying

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Characterization of 298 Patients with Lung Cancer Harboring MET Exon 14 Skipping Alterations Alexa B. Schrock, PhD, Garrett M. Frampton, PhD, James Suh, MD, Zachary R. Chalmers, BSc, Mark Rosenzweig, PhD, Rachel L. Erlich, PhD, Balazs Halmos, MD, Jonathan Goldman, MD, Patrick Forde, MD, Kurt Leuenberger, MD, Nir Peled, MD, PhD, Gregory P. Kalemkerian, MD, Jeffrey S. Ross, MD, Philip J. Stephens, PhD, Vincent A. Miller, MD, Siraj M. Ali, MD, PhD, Sai-Hong Ignatius Ou, MD, PhD Journal of Thoracic Oncology Volume 11, Issue 9, Pages 1493-1502 (September 2016) DOI: 10.1016/j.jtho.2016.06.004 Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

Figure 1 Schematic of all the genomic positions of hepatocyte growth factor receptor gene (MET) exon 14 skipping alterations. Alterations included base substitutions and insertions/deletions at the splice donor and acceptor sites, whole exon 14 deletion, and Y1003 mutation. Genomic positions with alterations occurring in more than one case are indicated with an asterisk (*) for two and the number of cases is greater than two. An octothorp (#) indicates samples with whole exon deletion of exon 14. Journal of Thoracic Oncology 2016 11, 1493-1502DOI: (10.1016/j.jtho.2016.06.004) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

Figure 2 Complete response to crizotinib in patient (case 3) with hepatocyte growth factor receptor gene (MET) exon 14 skipping alteration. Fludeoxyglucose F 18 positron emission tomography scan images (A) before crizotinib treatment image and with obvious metastatic disease (B) after 6 weeks of crizotinib treatment, at which time fludeoxyglucose F 18 uptake has been diminished significantly. Journal of Thoracic Oncology 2016 11, 1493-1502DOI: (10.1016/j.jtho.2016.06.004) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

Figure 3 Pre–crizotinib treatment and post–crizotinib treatment hematoxylin and eosin stain from a mediastinal lymph node from an adenocarcinoma harboring hepatocyte growth factor receptor gene (MET) exon 14 skipping alteration. (A and B) Before crizotinib low-(40X) (A) and high-magnification (200X) (B) hematoxylin and eosin–stained images of a metastatic lesion in a mediastinal lymph node showing retraction artifact seen in tumors with micropapillary features. (C and D) After 2 months of neoadjuvant crizotinib low-(40X) (C) and high-magnification (100X) (D) images showing extensive fibrosis in the resected primary lung tumor. Journal of Thoracic Oncology 2016 11, 1493-1502DOI: (10.1016/j.jtho.2016.06.004) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

Supplementary Figure 1 Journal of Thoracic Oncology 2016 11, 1493-1502DOI: (10.1016/j.jtho.2016.06.004) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

Supplementary Figure 2 Journal of Thoracic Oncology 2016 11, 1493-1502DOI: (10.1016/j.jtho.2016.06.004) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions