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第61巻第5号目次 | Japanese/English |
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─ 委員会報告 ─
METex14 Skipping Testing Guidance for Lung Cancer Patients: The Guidance from the Biomarker Committee, the Japan Lung Cancer Society
Yasushi Yatabe1, Koichi Goto2, Shingo Matsumoto2, Yutaka Hatanaka3, Naoko Arakane4, Sadakatsu Ikeda5, Akira Inoue6, Ichiro Kinoshita7, Hideharu Kimura8, Tomohiro Sakamoto9, Miyako Satouchi10, Junichi Shimizu11, Kuniko Sunami12, Koji Tsuta13, Shinichi Toyooka14, Kazuto Nishio15, Kazumi Nishino16, Masashi Mikubo17, Tomoyuki Yokose18, Hirotoshi Dosaka-Akita191Department of Diagnostic Pathology, National Cancer Center, Japan, 2Department of Thoracic Oncology, National Cancer Center Hospital East, Japan, 3Research Division of Genome Companion Diagnostics, Hokkaido University Hospital, Japan, 4Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Saga University, Japan, 5Center for Innovative Cancer Treatment, Tokyo Medical and Dental University, Japan, 6Department of Palliative Medicine, Tohoku University School of Medicine, Japan, 7Division of Clinical Cancer Genomics, Hokkaido University Hospital, Japan, 8Department of Respiratory Medicine, Kanazawa University, Japan, 9Division of Respiratory Medicine and Rheumatology, Department of Multidisciplinary Internal Medicine, Tottori University, Japan, 10Department of Thoracic Oncology, Hyogo Cancer Center, Japan, 11Department of Thoracic Oncology, Aichi Cancer Center Hospital, Japan, 12Department of Laboratory Medicine, National Cancer Center Hospital, Japan, 13Department of Pathology, Kansai Medical University, Japan, 14Department of General Thoracic Surgery, Breast and Endocrinological Surgery, Okayama University, Japan, 15Department of Genome Biology, Kindai University, Japan, 16Department of Thoracic Oncology, Osaka International Cancer Institute, Japan, 17Department of Thoracic Surgery, Kitasato University School of Medicine, Japan, 18Department of Pathology, Kanagawa Cancer Center, Japan, 19Department of Medical Oncology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Japan
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.
索引用語：Lung cancer, MET exon 14 skipping, Biomarker test, Companion diagnostic test
肺癌 61 (5)：361─370，2021
