Discordant HER2 Exon 20 Mutation Status Determines a Differential Sensitivity to Afatinib Chien-Hung Gow, MD, PhD, Wei-Yu Liao, MD, PhD, Yi-Nan Liu,

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Discordant HER2 Exon 20 Mutation Status Determines a Differential Sensitivity to Afatinib Chien-Hung Gow, MD, PhD, Wei-Yu Liao, MD, PhD, Yi-Nan Liu, PhD, Jin-Yuan Shih, MD, PhD Journal of Thoracic Oncology Volume 10, Issue 7, Pages e58-e60 (July 2015) DOI: 10.1097/JTO.0000000000000518 Copyright © 2015 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 1 A, B, Sequencing of exon 20 of HER2 reveals GGCTCCCCA insertion (P780_Y781insGSP; red font) in the primary lung tumor, although exon 20 in the metastatic brain tumor is wild-type. C, D, Computed tomography images show the patient’s lungs and brain after the failure of several chemotherapy agents, and before afatinib treatment. E, F, Computed tomography images of the patient’s lungs and brain show a significant response to afatinib treatment after 3 months in the primary right lower lung tumor, and disease progression in the right metastatic cerebellar tumor. Journal of Thoracic Oncology 2015 10, e58-e60DOI: (10.1097/JTO.0000000000000518) Copyright © 2015 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 2 A, Enhancing HER2 phosphorylation in Ba/F3 cells expressed the HER2 mutants. Whole cell lysates from H1299 (expressing wild-type HER2, as a control) and Ba/F3 cells expressing different HER2 mutants were collected for the detection of ErbB2, phospho-ErbB2 (p-ErbB2), and α-tubulin was used as loading controls. Data shown are representative of three independent experiments that yielded similar results. The p-ErbB2/ErbB2 ratio was similar in both HER2 mutants expressing cells, but was very low in wild-type HER2 expressing cells. B, Afatinib-dependent growth inhibition in Ba/F3 cells expressed the HER2 mutant. Ba/F3 cells expressing mutant P780_Y781insGSP or A775_G776insYVMA growing in the absence of interleukin-3, or expressing vector in the presence of interleukin-3 (as a control) were incubated with the indicated concentrations of afatinib for 72 hours. Cell viability was measured using the 3-(4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Points Average of two experiments (each performed in triplicate); bars standard deviation. Journal of Thoracic Oncology 2015 10, e58-e60DOI: (10.1097/JTO.0000000000000518) Copyright © 2015 International Association for the Study of Lung Cancer Terms and Conditions