Druggable Oncogene Fusions in Invasive Mucinous Lung Adenocarcinoma
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- Takashi Nakaoku
- Authors' Affiliations: Divisions of 1Genome Biology, 2Genetics, and 3Refractory Cancer Research, National Cancer Center Research Institute, Divisions of 4Pathology and Clinical Laboratories, 5Thoracic Surgery, and 6Thoracic Oncology, National Cancer Center Hospital, Chuo-ku; 7Department of Metabolic Disorder, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo; 8Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, Japan; 9Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland; and 10The Institute of Predictive and Personalized Medicine of Cancer (IMPPC), Barcelona, Spain
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- Koji Tsuta
- Authors' Affiliations: Divisions of 1Genome Biology, 2Genetics, and 3Refractory Cancer Research, National Cancer Center Research Institute, Divisions of 4Pathology and Clinical Laboratories, 5Thoracic Surgery, and 6Thoracic Oncology, National Cancer Center Hospital, Chuo-ku; 7Department of Metabolic Disorder, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo; 8Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, Japan; 9Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland; and 10The Institute of Predictive and Personalized Medicine of Cancer (IMPPC), Barcelona, Spain
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- Hitoshi Ichikawa
- Authors' Affiliations: Divisions of 1Genome Biology, 2Genetics, and 3Refractory Cancer Research, National Cancer Center Research Institute, Divisions of 4Pathology and Clinical Laboratories, 5Thoracic Surgery, and 6Thoracic Oncology, National Cancer Center Hospital, Chuo-ku; 7Department of Metabolic Disorder, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo; 8Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, Japan; 9Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland; and 10The Institute of Predictive and Personalized Medicine of Cancer (IMPPC), Barcelona, Spain
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- Kouya Shiraishi
- Authors' Affiliations: Divisions of 1Genome Biology, 2Genetics, and 3Refractory Cancer Research, National Cancer Center Research Institute, Divisions of 4Pathology and Clinical Laboratories, 5Thoracic Surgery, and 6Thoracic Oncology, National Cancer Center Hospital, Chuo-ku; 7Department of Metabolic Disorder, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo; 8Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, Japan; 9Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland; and 10The Institute of Predictive and Personalized Medicine of Cancer (IMPPC), Barcelona, Spain
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- Hiromi Sakamoto
- Authors' Affiliations: Divisions of 1Genome Biology, 2Genetics, and 3Refractory Cancer Research, National Cancer Center Research Institute, Divisions of 4Pathology and Clinical Laboratories, 5Thoracic Surgery, and 6Thoracic Oncology, National Cancer Center Hospital, Chuo-ku; 7Department of Metabolic Disorder, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo; 8Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, Japan; 9Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland; and 10The Institute of Predictive and Personalized Medicine of Cancer (IMPPC), Barcelona, Spain
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- Masato Enari
- Authors' Affiliations: Divisions of 1Genome Biology, 2Genetics, and 3Refractory Cancer Research, National Cancer Center Research Institute, Divisions of 4Pathology and Clinical Laboratories, 5Thoracic Surgery, and 6Thoracic Oncology, National Cancer Center Hospital, Chuo-ku; 7Department of Metabolic Disorder, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo; 8Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, Japan; 9Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland; and 10The Institute of Predictive and Personalized Medicine of Cancer (IMPPC), Barcelona, Spain
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- Koh Furuta
- Authors' Affiliations: Divisions of 1Genome Biology, 2Genetics, and 3Refractory Cancer Research, National Cancer Center Research Institute, Divisions of 4Pathology and Clinical Laboratories, 5Thoracic Surgery, and 6Thoracic Oncology, National Cancer Center Hospital, Chuo-ku; 7Department of Metabolic Disorder, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo; 8Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, Japan; 9Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland; and 10The Institute of Predictive and Personalized Medicine of Cancer (IMPPC), Barcelona, Spain
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- Yoko Shimada
- Authors' Affiliations: Divisions of 1Genome Biology, 2Genetics, and 3Refractory Cancer Research, National Cancer Center Research Institute, Divisions of 4Pathology and Clinical Laboratories, 5Thoracic Surgery, and 6Thoracic Oncology, National Cancer Center Hospital, Chuo-ku; 7Department of Metabolic Disorder, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo; 8Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, Japan; 9Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland; and 10The Institute of Predictive and Personalized Medicine of Cancer (IMPPC), Barcelona, Spain
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- Hideaki Ogiwara
- Authors' Affiliations: Divisions of 1Genome Biology, 2Genetics, and 3Refractory Cancer Research, National Cancer Center Research Institute, Divisions of 4Pathology and Clinical Laboratories, 5Thoracic Surgery, and 6Thoracic Oncology, National Cancer Center Hospital, Chuo-ku; 7Department of Metabolic Disorder, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo; 8Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, Japan; 9Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland; and 10The Institute of Predictive and Personalized Medicine of Cancer (IMPPC), Barcelona, Spain
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- Shun-ichi Watanabe
- Authors' Affiliations: Divisions of 1Genome Biology, 2Genetics, and 3Refractory Cancer Research, National Cancer Center Research Institute, Divisions of 4Pathology and Clinical Laboratories, 5Thoracic Surgery, and 6Thoracic Oncology, National Cancer Center Hospital, Chuo-ku; 7Department of Metabolic Disorder, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo; 8Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, Japan; 9Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland; and 10The Institute of Predictive and Personalized Medicine of Cancer (IMPPC), Barcelona, Spain
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- Hiroshi Nokihara
- Authors' Affiliations: Divisions of 1Genome Biology, 2Genetics, and 3Refractory Cancer Research, National Cancer Center Research Institute, Divisions of 4Pathology and Clinical Laboratories, 5Thoracic Surgery, and 6Thoracic Oncology, National Cancer Center Hospital, Chuo-ku; 7Department of Metabolic Disorder, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo; 8Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, Japan; 9Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland; and 10The Institute of Predictive and Personalized Medicine of Cancer (IMPPC), Barcelona, Spain
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- Kazuki Yasuda
- Authors' Affiliations: Divisions of 1Genome Biology, 2Genetics, and 3Refractory Cancer Research, National Cancer Center Research Institute, Divisions of 4Pathology and Clinical Laboratories, 5Thoracic Surgery, and 6Thoracic Oncology, National Cancer Center Hospital, Chuo-ku; 7Department of Metabolic Disorder, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo; 8Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, Japan; 9Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland; and 10The Institute of Predictive and Personalized Medicine of Cancer (IMPPC), Barcelona, Spain
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- Masaki Hiramoto
- Authors' Affiliations: Divisions of 1Genome Biology, 2Genetics, and 3Refractory Cancer Research, National Cancer Center Research Institute, Divisions of 4Pathology and Clinical Laboratories, 5Thoracic Surgery, and 6Thoracic Oncology, National Cancer Center Hospital, Chuo-ku; 7Department of Metabolic Disorder, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo; 8Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, Japan; 9Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland; and 10The Institute of Predictive and Personalized Medicine of Cancer (IMPPC), Barcelona, Spain
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- Takao Nammo
- Authors' Affiliations: Divisions of 1Genome Biology, 2Genetics, and 3Refractory Cancer Research, National Cancer Center Research Institute, Divisions of 4Pathology and Clinical Laboratories, 5Thoracic Surgery, and 6Thoracic Oncology, National Cancer Center Hospital, Chuo-ku; 7Department of Metabolic Disorder, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo; 8Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, Japan; 9Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland; and 10The Institute of Predictive and Personalized Medicine of Cancer (IMPPC), Barcelona, Spain
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- Teruhide Ishigame
- Authors' Affiliations: Divisions of 1Genome Biology, 2Genetics, and 3Refractory Cancer Research, National Cancer Center Research Institute, Divisions of 4Pathology and Clinical Laboratories, 5Thoracic Surgery, and 6Thoracic Oncology, National Cancer Center Hospital, Chuo-ku; 7Department of Metabolic Disorder, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo; 8Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, Japan; 9Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland; and 10The Institute of Predictive and Personalized Medicine of Cancer (IMPPC), Barcelona, Spain
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- Aaron J. Schetter
- Authors' Affiliations: Divisions of 1Genome Biology, 2Genetics, and 3Refractory Cancer Research, National Cancer Center Research Institute, Divisions of 4Pathology and Clinical Laboratories, 5Thoracic Surgery, and 6Thoracic Oncology, National Cancer Center Hospital, Chuo-ku; 7Department of Metabolic Disorder, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo; 8Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, Japan; 9Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland; and 10The Institute of Predictive and Personalized Medicine of Cancer (IMPPC), Barcelona, Spain
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- Hirokazu Okayama
- Authors' Affiliations: Divisions of 1Genome Biology, 2Genetics, and 3Refractory Cancer Research, National Cancer Center Research Institute, Divisions of 4Pathology and Clinical Laboratories, 5Thoracic Surgery, and 6Thoracic Oncology, National Cancer Center Hospital, Chuo-ku; 7Department of Metabolic Disorder, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo; 8Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, Japan; 9Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland; and 10The Institute of Predictive and Personalized Medicine of Cancer (IMPPC), Barcelona, Spain
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- Curtis C. Harris
- Authors' Affiliations: Divisions of 1Genome Biology, 2Genetics, and 3Refractory Cancer Research, National Cancer Center Research Institute, Divisions of 4Pathology and Clinical Laboratories, 5Thoracic Surgery, and 6Thoracic Oncology, National Cancer Center Hospital, Chuo-ku; 7Department of Metabolic Disorder, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo; 8Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, Japan; 9Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland; and 10The Institute of Predictive and Personalized Medicine of Cancer (IMPPC), Barcelona, Spain
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- Young Hak Kim
- Authors' Affiliations: Divisions of 1Genome Biology, 2Genetics, and 3Refractory Cancer Research, National Cancer Center Research Institute, Divisions of 4Pathology and Clinical Laboratories, 5Thoracic Surgery, and 6Thoracic Oncology, National Cancer Center Hospital, Chuo-ku; 7Department of Metabolic Disorder, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo; 8Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, Japan; 9Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland; and 10The Institute of Predictive and Personalized Medicine of Cancer (IMPPC), Barcelona, Spain
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- Michiaki Mishima
- Authors' Affiliations: Divisions of 1Genome Biology, 2Genetics, and 3Refractory Cancer Research, National Cancer Center Research Institute, Divisions of 4Pathology and Clinical Laboratories, 5Thoracic Surgery, and 6Thoracic Oncology, National Cancer Center Hospital, Chuo-ku; 7Department of Metabolic Disorder, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo; 8Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, Japan; 9Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland; and 10The Institute of Predictive and Personalized Medicine of Cancer (IMPPC), Barcelona, Spain
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- Jun Yokota
- Authors' Affiliations: Divisions of 1Genome Biology, 2Genetics, and 3Refractory Cancer Research, National Cancer Center Research Institute, Divisions of 4Pathology and Clinical Laboratories, 5Thoracic Surgery, and 6Thoracic Oncology, National Cancer Center Hospital, Chuo-ku; 7Department of Metabolic Disorder, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo; 8Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, Japan; 9Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland; and 10The Institute of Predictive and Personalized Medicine of Cancer (IMPPC), Barcelona, Spain
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- Teruhiko Yoshida
- Authors' Affiliations: Divisions of 1Genome Biology, 2Genetics, and 3Refractory Cancer Research, National Cancer Center Research Institute, Divisions of 4Pathology and Clinical Laboratories, 5Thoracic Surgery, and 6Thoracic Oncology, National Cancer Center Hospital, Chuo-ku; 7Department of Metabolic Disorder, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo; 8Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, Japan; 9Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland; and 10The Institute of Predictive and Personalized Medicine of Cancer (IMPPC), Barcelona, Spain
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- Takashi Kohno
- Authors' Affiliations: Divisions of 1Genome Biology, 2Genetics, and 3Refractory Cancer Research, National Cancer Center Research Institute, Divisions of 4Pathology and Clinical Laboratories, 5Thoracic Surgery, and 6Thoracic Oncology, National Cancer Center Hospital, Chuo-ku; 7Department of Metabolic Disorder, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo; 8Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, Japan; 9Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland; and 10The Institute of Predictive and Personalized Medicine of Cancer (IMPPC), Barcelona, Spain
Description
<jats:title>Abstract</jats:title> <jats:p>Purpose: To identify druggable oncogenic fusions in invasive mucinous adenocarcinoma (IMA) of the lung, a malignant type of lung adenocarcinoma in which KRAS mutations frequently occur.</jats:p> <jats:p>Experimental Design: From an IMA cohort of 90 cases, consisting of 56 cases (62%) with KRAS mutations and 34 cases without (38%), we conducted whole-transcriptome sequencing of 32 IMAs, including 27 cases without KRAS mutations. We used the sequencing data to identify gene fusions, and then performed functional analyses of the fusion gene products.</jats:p> <jats:p>Results: We identified oncogenic fusions that occurred mutually exclusively with KRAS mutations: CD74-NRG1, SLC3A2-NRG1, EZR-ERBB4, TRIM24-BRAF, and KIAA1468-RET. NRG1 fusions were present in 17.6% (6/34) of KRAS-negative IMAs. The CD74-NRG1 fusion activated HER2:HER3 signaling, whereas the EZR-ERBB4 and TRIM24-BRAF fusions constitutively activated the ERBB4 and BRAF kinases, respectively. Signaling pathway activation and fusion-induced anchorage-independent growth/tumorigenicity of NIH3T3 cells expressing these fusions were suppressed by tyrosine kinase inhibitors approved for clinical use.</jats:p> <jats:p>Conclusions: Oncogenic fusions act as driver mutations in IMAs without KRAS mutations, and thus represent promising therapeutic targets for the treatment of such IMAs. Clin Cancer Res; 20(12); 3087–93. ©2014 AACR.</jats:p>
Journal
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- Clinical Cancer Research
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Clinical Cancer Research 20 (12), 3087-3093, 2014-06-12
American Association for Cancer Research (AACR)
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Details 詳細情報について
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- CRID
- 1360283693661675520
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- ISSN
- 15573265
- 10780432
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- Data Source
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- Crossref
- KAKEN