title: Identification of CCDC6-RET fusion in the human lung adenocarcinoma cell line, LC-2/ad.
abstract: Rearranged during transfection (RET) fusions have been newly identified in approximately 1% of patients with primary lung tumors. However, patient-derived lung cancer cell lines harboring RET fusions have not yet been established or identified, and therefore, the effectiveness of an RET inhibitor on lung tumors with endogenous RET fusion has not yet been studied. In this study, we report identification of CCDC6-RET fusion in the human lung adenocarcinoma cell line LC-2/ad. LC-2/ad showed distinctive sensitivity to the RET inhibitor, vandetanib, among 39 non-small lung cancer cell lines. The xenograft tumor of LC-2/ad showed cribriform acinar structures, a morphologic feature of primary RET fusion-positive lung adenocarcinomas. LC-2/ad cells could provide useful resources to analyze molecular functions of RET-fusion protein and its response to RET inhibitors.
authors.affiliation: Department of Pathology, Division of Integrative Pathology, Jichi Medical University, Shimotsuke, Tochigi, Japan; Department of Cancer Biology, Division of Molecular Pathology, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Matsubara
authors.affiliation: Department of Surgery, Division of General Thoracic Surgery, Jichi Medical University, Tochigi, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Kanai
authors.affiliation: Department of Human Pathology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku Tokyo.
authors.forename: Shumpei
authors.initials: S
authors.lastname: Ishikawa
authors.affiliation: Department of Pathology, Division of Integrative Pathology, Jichi Medical University, Shimotsuke, Tochigi, Japan.
authors.forename: Shiori
authors.initials: S
authors.lastname: Ohara
authors.affiliation: Department of Pathology, Division of Integrative Pathology, Jichi Medical University, Shimotsuke, Tochigi, Japan.
authors.forename: Taichiro
authors.initials: T
authors.lastname: Yoshimoto
authors.affiliation: Department of Pathology, Division of Integrative Pathology, Jichi Medical University, Shimotsuke, Tochigi, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sakatani
authors.affiliation: Department of Pathology, Division of Integrative Pathology, Jichi Medical University, Shimotsuke, Tochigi, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Oguni
authors.affiliation: Department of Pathology, Division of Integrative Pathology, Jichi Medical University, Shimotsuke, Tochigi, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Tamura
authors.affiliation: Department of Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kataoka
authors.affiliation: Department of Surgery, Division of General Thoracic Surgery, Jichi Medical University, Tochigi, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Endo
authors.affiliation: Department of Cancer Biology, Division of Molecular Pathology, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Murakami
authors.affiliation: Laboratory for Systems Biology and Medicine, Division of Genome Science, Research Center for Advanced Science and Technology, The University of Tokyo, Meguro-ku, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Aburatani
authors.affiliation: Department of Human Pathology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku Tokyo.
authors.forename: Masashi
authors.initials: M
authors.lastname: Fukayama
authors.affiliation: Department of Pathology, Division of Integrative Pathology, Jichi Medical University, Shimotsuke, Tochigi, Japan. Electronic address: tniki@jichi.ac.jp.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Niki
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D003598:Cytoskeletal Proteins / Q000235:genetics*; D005260:Female; D000077156:Gefitinib; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D010766:Phosphorylation / Q000187:drug effects; D010880:Piperidines / Q000008:administration & dosage; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D011799:Quinazolines / Q000008:administration & dosage; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
chemical_list: C088832:CCDC6 protein, human; D003598:Cytoskeletal Proteins; D015514:Oncogene Proteins, Fusion; D010880:Piperidines; D011799:Quinazolines; D012333:RNA, Messenger; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; D000077156:Gefitinib; C452423:vandetanib