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Identification of a Novel HIP1-ALK Fusion Variant in Non–Small-Cell Lung Cancer (NSCLC) and Discovery of ALK I1171 (I1171N/S) Mutations in Two ALK-Rearranged.

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Presentation on theme: "Identification of a Novel HIP1-ALK Fusion Variant in Non–Small-Cell Lung Cancer (NSCLC) and Discovery of ALK I1171 (I1171N/S) Mutations in Two ALK-Rearranged."— Presentation transcript:

1 Identification of a Novel HIP1-ALK Fusion Variant in Non–Small-Cell Lung Cancer (NSCLC) and Discovery of ALK I1171 (I1171N/S) Mutations in Two ALK-Rearranged NSCLC Patients with Resistance to Alectinib  Sai-Hong Ignatius Ou, MD, PhD, Samuel J. Klempner, MD, Joel R. Greenbowe, BS, Michele Azada, MPH, Alexa B. Schrock, PhD, Siraj M. Ali, MD, PhD, Jeffrey S. Ross, MD, Philip J. Stephens, PhD, Vincent A. Miller, MD  Journal of Thoracic Oncology  Volume 9, Issue 12, Pages (December 2014) DOI: /JTO Copyright © 2014 International Association for the Study of Lung Cancer Terms and Conditions

2 FIGURE 1 A, Prealectinib positron emission tomography-computed tomography scan treatment of the patient (case 1) showing disease progression in the mediastinum and lungs but no liver involvement. The red circle indicated the location of metastatic disease upon progression with crizotinib. B, Serial computed tomography of the abdomen of the patient (case 1) showing the appearance of several liver lesions after 12 months of alectinib treatment. The red circle represents where the rebiopsy of the tumor was performed. C, Prealectinib baseline scan and on-treatment scan of patient (case 2) which showed the emergence of a new liver metastasis after 12 months of alectinib treatment. Arrows indicate liver metastasis. Journal of Thoracic Oncology 2014 9, DOI: ( /JTO ) Copyright © 2014 International Association for the Study of Lung Cancer Terms and Conditions

3 FIGURE 2 Diagrammatic representation of the rearrangement involved exons 1 to 30 of Huntingtin-interacting protein 1 (HIP1) and exons 20 to 29 of anaplastic lymphoma kinase (ALK). Two previously identified HIP1-ALK fusion variants were also shown. ANTH, AP180 N-terminal; CC, coiled coil domain of the HIP1 protein; TH, talin-homology. Journal of Thoracic Oncology 2014 9, DOI: ( /JTO ) Copyright © 2014 International Association for the Study of Lung Cancer Terms and Conditions

4 FIGURE 3 A, Diagrammatic representation of the I1171N mutation identified from case 1 indicating approximately 15% of the next generation sequencing run showed the presence of resistant I1171N substitution. B, Diagrammatic representation of the I1171S mutation identified from case 2 indicating approximately 36% of the next-generation sequencing run showed the presence of resistant I1171S substitution. Journal of Thoracic Oncology 2014 9, DOI: ( /JTO ) Copyright © 2014 International Association for the Study of Lung Cancer Terms and Conditions

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