METex14 Skipping Testing Guidance for Lung Cancer Patients: The Guidance from the Biomarker Committee, the Japan Lung Cancer Society

  • Yatabe Yasushi
    Department of Diagnostic Pathology, National Cancer Center
  • Goto Koichi
    Department of Thoracic Oncology, National Cancer Center Hospital East
  • Matsumoto Shingo
    Department of Thoracic Oncology, National Cancer Center Hospital East
  • Hatanaka Yutaka
    Research Division of Genome Companion Diagnostics, Hokkaido University Hospital
  • Arakane Naoko
    Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Saga University
  • Ikeda Sadakatsu
    Center for Innovative Cancer Treatment, Tokyo Medical and Dental University
  • Inoue Akira
    Department of Palliative Medicine, Tohoku University School of Medicine
  • Kinoshita Ichiro
    Division of Clinical Cancer Genomics, Hokkaido University Hospital
  • Kimura Hideharu
    Department of Respiratory Medicine, Kanazawa University
  • Sakamoto Tomohiro
    Division of Respiratory Medicine and Rheumatology, Department of Multidisciplinary Internal Medicine, Tottori University
  • Satouchi Miyako
    Department of Thoracic Oncology, Hyogo Cancer Center
  • Shimizu Junichi
    Department of Thoracic Oncology, Aichi Cancer Center Hospital
  • Sunami Kuniko
    Department of Laboratory Medicine, National Cancer Center Hospital
  • Tsuta Koji
    Department of Pathology, Kansai Medical University
  • Toyooka Shinichi
    Department of General Thoracic Surgery, Breast and Endocrinological Surgery, Okayama University
  • Nishio Kazuto
    Department of Genome Biology, Kindai University
  • Nishino Kazumi
    Department of Thoracic Oncology, Osaka International Cancer Institute
  • Mikubo Masashi
    Department of Thoracic Surgery, Kitasato University School of Medicine
  • Yokose Tomoyuki
    Department of Pathology, Kanagawa Cancer Center
  • Dosaka-Akita Hirotoshi
    Department of Medical Oncology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University

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抄録

<p>MET, a proto-oncogene located in 7q21-q31, encodes a receptor tyrosine kinase, of which mutations, amplification, fusions and overexpression are reported to be associated with oncogenesis. MET exon 14 (METex14) skipping is one of such MET alterations, and this abnormality is caused by genetic deletions or mutations in the intron/exon boundary sites as splice-site abnormalities, resulting in the generation of a deleted transcript in exon 14. This exon encodes juxtamembrane domain, which contains the binding site of c-Cbl E3 ubiquitin ligase. Therefore, lack of METex14 suppresses ubiquitination and degradation, which lead to functional MET activation. In 2020, tepotinib and capmatinib were approved for the treatment of advanced recurrent lung cancer with this alteration. To implement the molecular testing to detect METex14 skipping in clinical practice, a practical guidance was released from the Biomarker Committee of the Japan Lung Cancer Society, and the content is introduced in this article.</p>

収録刊行物

  • 肺癌

    肺癌 61 (5), 361-370, 2021-10-20

    特定非営利活動法人 日本肺癌学会

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