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      Novel NLRC4‐ALK and EML4‐ALK double fusion mutations in a lung adenocarcinoma patient: A case report

      case-report

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          Abstract

          Anaplastic lymphoma kinase ( ALK) rearrangements have been reported in 5% to 6% of non‐small cell lung cancer (NSCLC) patients. However, the concurrent existence of two ALK fusions within the same patient have rarely previously been reported. Moreover, considering the diversities of ALK mutations, it is necessary to evaluate the response of both double and new types of ALK fusions to ALK‐tyrosine kinase inhibitors (ALK‐TKIs). Here, we report a case of a 64‐year‐old Chinese woman who was diagnosed with lung adenocarcinoma (ADC) who concurrently harbored two types of ALK‐rearrangements, including an unreported NLRC4‐ALK fusion and EML4‐ALK fusion. After surgery, the patient had a progression‐free survival (PFS) of over 10 months with continuous crizotinib treatment after surgery. Our findings provide a better understanding of ALK‐TKI in patients with two novel ALK concomitant fusions.

          Key points

          A lung adenocarcinoma patient harboring concurrent NLRC4‐ALK and EML4‐ALK fusion mutations benefited from crizotinib after surgery. Our findings provide important information for future treatment decision‐making in patients with double ALK fusions.

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          Most cited references8

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          Lorlatinib in patients with ALK-positive non-small-cell lung cancer: results from a global phase 2 study

          Lorlatinib is a potent, brain-penetrant, third-generation inhibitor of ALK and ROS1 tyrosine kinases with broad coverage of ALK mutations. In a phase 1 study, activity was seen in patients with ALK-positive non-small-cell lung cancer, most of whom had CNS metastases and progression after ALK-directed therapy. We aimed to analyse the overall and intracranial antitumour activity of lorlatinib in patients with ALK-positive, advanced non-small-cell lung cancer.
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            Genomic alterations in lung adenocarcinoma.

            Treatment for non-small-cell lung cancer is evolving from the use of cytotoxic chemotherapy to personalised treatment based on molecular alterations. This past decade has witnessed substantial progress in the treatment of patients with EGFR mutations and ALK rearrangements, and it is now possible to study complex genomic alterations in cancer using next-generation sequencing. Sequencing data from large-scale consortia, such as The Cancer Genome Atlas, as well as several independent groups, have helped identify novel drivers and potentially targetable alterations in lung adenocarcinomas. These data clearly suggest that lung adenocarcinoma is associated with distinct genomic alterations compared with other lung cancer subtypes, and highlight the widespread molecular heterogeneity that underlies the disease. In this Review, we discuss some of the key findings from genomic studies of lung adenocarcinoma.
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              ALK‐ rearrangement in non‐small‐cell lung cancer (NSCLC)

              The ALK gene encodes a transmembrane tyrosine kinase receptor. ALK is physiologically expressed in the nervous system during embryogenesis, but its expression decreases postnatally. ALK first emerged in the field of oncology in 1994 when it was identified to fuse to NPM1 in anaplastic large‐cell lymphoma. Since then, ALK has been associated with other types of cancers, including non‐small‐cell lung cancer (NSCLC). More than 19 different ALK fusion partners have been discovered in NSCLC, including EML4, KIF5B, KLC1, and TPR. Most of these ALK fusions in NSCLC patients respond well to the ALK inhibitor, crizotinib. In this paper, we reviewed fusion partner genes with ALK, detection methods for ALK‐rearrangement (ALK‐R), and the ALK‐tyrosine kinase inhibitor, crizotinib, used in NSCLC patients.
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                Author and article information

                Contributors
                wuxueqian94@gmail.com
                lidan@wchscu.cn
                Journal
                Thorac Cancer
                Thorac Cancer
                10.1111/(ISSN)1759-7714
                TCA
                Thoracic Cancer
                John Wiley & Sons Australia, Ltd (Melbourne )
                1759-7706
                1759-7714
                24 March 2020
                June 2020
                : 11
                : 6 ( doiID: 10.1111/tca.v11.6 )
                : 1695-1698
                Affiliations
                [ 1 ] Department of Thoracic Oncology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital Sichuan University and Collaborative Innovation Center Chengdu China
                [ 2 ] Department of Pathology, West China Hospital Sichuan University Chengdu China
                [ 3 ] Department of Oncology The Second Affiliated Hospital of Chongqing Medical University Chongqing China
                [ 4 ] Institute of Drug Clinical Trial, West China Hospital Sichuan University Chengdu China
                [ 5 ] Precision Medicine Center, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital Sichuan University Chengdu China
                Author notes
                [*] [* ] Correspondence

                Dan Li, Precision Medicine Center, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu 610041, China.

                Tel: +86 28 8516 4165

                Fax: +86 28 8516 4165

                Email: lidan@ 123456wchscu.cn

                Author information
                https://orcid.org/0000-0001-6375-3753
                https://orcid.org/0000-0001-7450-0006
                https://orcid.org/0000-0002-9507-9844
                Article
                TCA13389
                10.1111/1759-7714.13389
                7262889
                32212216
                46477c58-b49c-468e-b260-656d5c075ff4
                © 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 21 December 2019
                : 19 February 2020
                : 20 February 2020
                Page count
                Figures: 3, Tables: 0, Pages: 4, Words: 1679
                Funding
                Funded by: National Science and Technology Major Project
                Award ID: 2017ZX09304023
                Categories
                Case Report
                Case Reports
                Custom metadata
                2.0
                June, 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.3 mode:remove_FC converted:01.06.2020

                crizotinib,double alk fusions,eml4‐alk,lung adenocarcinoma,nlrc4‐alk

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