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Updated: May 16, 2026
Lung Tumor Cell Recruitment Assay
Published on: February 26, 2019
Identification of CCDC6-RET fusion in the human lung adenocarcinoma cell line, LC-2/ad
Daisuke Matsubara1, Yoshihiko Kanai2, Shumpei Ishikawa3
1Department 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.
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.
Insights
Researchers identified a Rearranged during transfection (RET) fusion in a lung cancer cell line. This cell line demonstrated sensitivity to the RET inhibitor vandetanib, offering a new model for studying RET-driven lung tumors.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Rearranged during transfection (RET) fusions are emerging oncogenic drivers in a subset of lung cancers.
- Lack of patient-derived cell lines with endogenous RET fusions has hindered the study of RET inhibitor efficacy.
- Understanding RET fusion-positive lung adenocarcinoma is critical for targeted therapy development.
Purpose of the Study:
- To identify and characterize a novel human lung cancer cell line harboring a RET fusion.
- To evaluate the sensitivity of this cell line to RET inhibitors.
- To establish a preclinical model for investigating RET-driven lung adenocarcinoma.
Main Methods:
- Screening of 39 non-small cell lung cancer cell lines for RET fusions.
- Identification of CCDC6-RET fusion in the LC-2/ad cell line.
- Assessment of vandetanib sensitivity in vitro and in vivo using xenograft models.
Main Results:
- The human lung adenocarcinoma cell line LC-2/ad was identified to harbor a CCDC6-RET fusion.
- LC-2/ad cells exhibited significant sensitivity to the RET inhibitor vandetanib.
- LC-2/ad xenograft tumors displayed cribriform acinar structures, mimicking primary RET fusion-positive lung adenocarcinomas.
Conclusions:
- The LC-2/ad cell line represents the first patient-derived model of lung adenocarcinoma with an endogenous RET fusion.
- This model demonstrates the therapeutic potential of RET inhibitors like vandetanib in RET fusion-driven lung cancers.
- LC-2/ad cells provide a valuable resource for further research into RET fusion molecular mechanisms and targeted therapies.
