Jamie A. Saxon, PhD, Lynette M. Sholl, MD, Pasi A. Jänne, MD, PhD

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EGFR L858M/L861Q cis Mutations Confer Selective Sensitivity to Afatinib Jamie A. Saxon, PhD, Lynette M. Sholl, MD, Pasi A. Jänne, MD, PhD Journal of Thoracic Oncology Volume 12, Issue 5, Pages 884-889 (May 2017) DOI: 10.1016/j.jtho.2017.01.006 Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions

Figure 1 Identification of EGFR L858M and L861Q mutations in cis from lung cancer tumor biopsy. Alignment of next-generation sequencing reads from the patient’s tumor reveals the 2572C → A and 2582T → A nucleotide substitutions resulting in L858M and L861Q missense mutations in exon 21 of EGFR. These substitutions co-occurred in the same reads, indicating that the mutations are in cis. Abbreviation: bp, base pair. Journal of Thoracic Oncology 2017 12, 884-889DOI: (10.1016/j.jtho.2017.01.006) Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions

Figure 2 Computed tomography scans of a patient with NSCLC exhibiting primary resistance to erlotinib and subsequent response to afatinib. Coronal and transverse computed tomography scan images at baseline before treatment, after 2 months of erlotinib treatment, and after 2 months of afatinib treatment. Journal of Thoracic Oncology 2017 12, 884-889DOI: (10.1016/j.jtho.2017.01.006) Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions

Figure 3 In vitro studies demonstrate reduced sensitivity of EGFR L858M/L861Q to gefitinib and osimertinib compared with EGFR L858R. Viability of EGFR L858R (A) and EGFR L858M/L861Q Ba/F3 (B) cells after 72 hours of treatment with gefinitib, osimertinib, and afatinib detected by MTS assay. Error bars represent standard error of the mean. (C) Immunoblotting of lysates from EGFR L858R and EGFR L858M/L861Q NIH-3T3 cells treated with the indicated concentrations of gefitinib, osimertinib, or afatinib. The ratio of phospho-EGFR in treated versus untreated samples was quantified by densitometry for each cell line. Journal of Thoracic Oncology 2017 12, 884-889DOI: (10.1016/j.jtho.2017.01.006) Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions