Secondary Mutations at I1171 in the ALK Gene Confer Resistance to Both Crizotinib and Alectinib Gouji Toyokawa, MD, PhD, Fumihiko Hirai, MD, PhD, Eiko.

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Secondary Mutations at I1171 in the ALK Gene Confer Resistance to Both Crizotinib and Alectinib Gouji Toyokawa, MD, PhD, Fumihiko Hirai, MD, PhD, Eiko Inamasu, MD, Tsukihisa Yoshida, MD, Kaname Nosaki, MD, Tomoyoshi Takenaka, MD, PhD, Masafumi Yamaguchi, MD, PhD, Takashi Seto, MD, PhD, Mitsuhiro Takenoyama, MD, PhD, Yukito Ichinose, MD, PhD Journal of Thoracic Oncology Volume 9, Issue 12, Pages e86-e87 (December 2014) DOI: 10.1097/JTO.0000000000000358 Copyright © 2014 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 1 Direct sequencing by capillary electrophoresis of a biopsy sample obtained from the left clavicle before crizotinib treatment using an ABI PRISM 310 Genetic Analyzer (A). Computed tomography scans showed metastatic mediastinal lymph nodes before (B) and approximately 7 months after the administration of crizotinib (C). There was expansion of the pleural effusion with no relapse of the mediastinal lymph nodes (D). Direct sequencing of a biopsy sample of pleural effusion after a relapse on crizotinib identified a secondary mutation of the ALK gene at codon 1171 (I1171T) (E). Journal of Thoracic Oncology 2014 9, e86-e87DOI: (10.1097/JTO.0000000000000358) Copyright © 2014 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 2 Direct sequencing by capillary electrophoresis of a biopsy sample obtained from the skin metastasis before the administration of alectinib using an ABI PRISM 310 Genetic Analyzer (A). Computed tomography scans showing the primary lesion in the right lower lobe and hepatic metastases before (B) and approximately 4 months after (C) the administration of alectinib. A computed tomography scan indicating the relapse of the primary lesion and hepatic metastases approximately 7 months after the administration of alectinib (D). Direct sequencing of a biopsy sample obtained from the hepatic metastasis after a relapse on alectinib showing a secondary mutation of the ALK gene at codon 1171 (I1171N) (E). Journal of Thoracic Oncology 2014 9, e86-e87DOI: (10.1097/JTO.0000000000000358) Copyright © 2014 International Association for the Study of Lung Cancer Terms and Conditions