Expanded Circulating Tumor Cells from a Patient with ALK-Positive Lung Cancer Present with EML4-ALK Rearrangement Along with Resistance Mutation and Enable.

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Expanded Circulating Tumor Cells from a Patient with ALK-Positive Lung Cancer Present with EML4-ALK Rearrangement Along with Resistance Mutation and Enable Drug Sensitivity Testing: A Case Study Zhuo Zhang, PhD, Hiroe Shiratsuchi, PhD, Nallasivam Palanisamy, PhD, Sunitha Nagrath, PhD, Nithya Ramnath, M.B.B.S. Journal of Thoracic Oncology Volume 12, Issue 2, Pages 397-402 (February 2017) DOI: 10.1016/j.jtho.2016.07.027 Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

Figure 1 Tumor status of the patient. (A) Computed tomography scan at initial diagnosis and when the patient was resistant to crizotinib. (B) EML4-ALK rearrangement is detected in the tumor biopsy specimen (indicated by the arrowheads) at the initial visit by fluorescence in situ hybridization (original magnification, ×1000). Journal of Thoracic Oncology 2017 12, 397-402DOI: (10.1016/j.jtho.2016.07.027) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

Figure 2 Mutation analysis of expanded circulating tumor cells (CTCs). Expanded CTCs, during the three clinical visits, are positive for EML4-ALK rearrangement by fluorescence in situ hybridization (original magnification, ×1000). Arrows point toward the CTCs harboring EML4-ALK. DNA sequencing revealed a L1196M mutation in expanded CTCs when the patient developed resistance to crizotinib (on the second visit) and an absence of the mutation when brain metastasis occurred (on the third visit). Journal of Thoracic Oncology 2017 12, 397-402DOI: (10.1016/j.jtho.2016.07.027) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

Figure 3 Half maximal inhibitory concentrations of cells treated with crizotinib and ceritinib. Expanded circulating tumor cells (CTCs) are compared with pure cancer-associated fibroblasts (CAFs), a resistant cell line (i.e., A549), and a sensitive cell line (i.e., H3122). Journal of Thoracic Oncology 2017 12, 397-402DOI: (10.1016/j.jtho.2016.07.027) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions