Identification of CCDC6-RET fusion in the human lung adenocarcinoma cell line, LC-2/ad

Daisuke Matsubara; Yoshihiko Kanai; Shumpei Ishikawa; Shiori Ohara; Taichiro Yoshimoto; Takashi Sakatani; Sachiko Oguni; Tomoko Tamura; Hiroaki Kataoka; Shunsuke Endo; Yoshinori Murakami; Hiroyuki Aburatani; Masashi Fukayama; Toshiro Niki

doi:10.1097/JTO.0b013e3182721ed1

Identification of CCDC6-RET fusion in the human lung adenocarcinoma cell line, LC-2/ad

J Thorac Oncol. 2012 Dec;7(12):1872-1876. doi: 10.1097/JTO.0b013e3182721ed1.

Authors

Affiliations

¹ 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.
² Department of Surgery, Division of General Thoracic Surgery, Jichi Medical University, Tochigi, Japan.
³ Department of Human Pathology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku Tokyo.
⁴ Department of Pathology, Division of Integrative Pathology, Jichi Medical University, Shimotsuke, Tochigi, Japan.
⁵ Department of Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
⁶ Department of Cancer Biology, Division of Molecular Pathology, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo.
⁷ 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.
⁸ Department of Pathology, Division of Integrative Pathology, Jichi Medical University, Shimotsuke, Tochigi, Japan. Electronic address: tniki@jichi.ac.jp.

PMID: 23154560
DOI: 10.1097/JTO.0b013e3182721ed1

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma / drug therapy
Adenocarcinoma / genetics*
Adenocarcinoma / pathology
Animals
Antineoplastic Combined Chemotherapy Protocols / pharmacology
Blotting, Western
Carcinoma, Non-Small-Cell Lung / drug therapy
Carcinoma, Non-Small-Cell Lung / genetics*
Carcinoma, Non-Small-Cell Lung / pathology
Cell Proliferation / drug effects
Cytoskeletal Proteins / genetics*
Female
Gefitinib
Humans
Immunoenzyme Techniques
Lung Neoplasms / drug therapy
Lung Neoplasms / genetics*
Lung Neoplasms / pathology
Mice
Mice, Inbred NOD
Mice, SCID
Oncogene Proteins, Fusion / genetics*
Phosphorylation / drug effects
Piperidines / administration & dosage
Proto-Oncogene Proteins c-ret / genetics*
Quinazolines / administration & dosage
RNA, Messenger / genetics
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Transplantation, Heterologous
Tumor Cells, Cultured

Substances

CCDC6 protein, human
Cytoskeletal Proteins
Oncogene Proteins, Fusion
Piperidines
Quinazolines
RNA, Messenger
Proto-Oncogene Proteins c-ret
RET protein, human
Gefitinib
vandetanib