RET, ROS1 and ALK fusions in lung cancer
Abstract
Through an integrated molecular- and histopathology-based screening system, we performed a screening for fusions of anaplastic lymphoma kinase (ALK) and c-ros oncogene 1, receptor tyrosine kinase (ROS1) in 1,529 lung cancers and identified 44 ALK-fusion-positive and 13 ROS1-fusion-positive adenocarcinomas, including for unidentified fusion partners for ROS1. In addition, we discovered previously unidentified kinase fusions that may be promising for molecular-targeted therapy, kinesin family member 5B (KIF5B)-ret proto-oncogene (RET) and coiled-coil domain containing 6 (CCDC6)-RET, in 14 adenocarcinomas. A multivariate analysis of 1,116 adenocarcinomas containing these 71 kinase-fusion-positive adenocarcinomas identified four independent factors that are indicators of poor prognosis: age ≥ 50 years, male sex, high pathological stage and negative kinase-fusion status.
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The incidence of uncommon EGFR mutations is comparable to rare targetable driver genes such as ROS1 and RET.
“The need for appropriate management of patients with these uncommon mutations is increasing because the incidence of uncommon EGFR mutations is comparable to rare targetable driver genes such as ROS1 and RET.12, 13, 14, 15”
From Not all epidermal growth factor receptor mutations in lung cancer are created equal: Perspectives for individualized treatment strategy (2016) · cites this paper as [12]
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- Authors
- Takeuchi, K., Soda, M., Togashi, Y., Suzuki, R., Sakata, S., Hatano, S., Asaka, R., Hamanaka, W., Ninomiya, H., Uehara, H., Lim Choi, Y., Satoh, Y., Okumura, S., Nakagawa, K., Mano, H., & Ishikawa, Y.
- Affiliations
- Japanese Foundation For Cancer Research (JP)
- Jichi Medical University (JP)
- Nagoya University (JP)
- The Cancer Institute Hospital (JP)
- Corresponding author
- Takeuchi, Kengo
- ORCID
- Venue
- Nature Medicine
- Published
- 2012-02-12
- Volume
- 18
- Issue
- 3
- Pages
- 378-381
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2065799563
- Cited by
- 1,320
- References
- 19
- Citations by year
- 2026: 29 · 2025: 48 · 2024: 55 · 2023: 70 · 2022: 80 · 2021: 80 · 2020: 103 · 2019: 88 · 2018: 97 · 2017: 105 · 2016: 100 · 2015: 118 · 2014: 132 · 2013: 141 · 2012: 73
- FWCI
- 119.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (22300326, 22680063, 21591239)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Keywords
- RET fusion, ROS1 rearrangement, ALK fusion, lung adenocarcinoma, KIF5B-RET fusion, CCDC6-RET fusion, kinase fusions, targeted therapy, prognostic factors
- MeSH terms
- Adenocarcinoma of Lung, Anaplastic Lymphoma Kinase, Proto-Oncogene Mas, Adenocarcinoma, Adult, Age Factors, Aged, Aged, 80 and over, Animals, Cell Transformation, Neoplastic, Cytoskeletal Proteins, Female, Humans, Lung Neoplasms, Male, Middle Aged, Neoplasm Staging, Piperidines, Prognosis, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Quinazolines, Sex Factors, Oncogene Proteins, Fusion, Gene Expression Regulation, Neoplastic, 3T3 Cells, Receptor Protein-Tyrosine Kinases, Cell Line, Tumor, Cell Proliferation, Proto-Oncogene Proteins c-ret, Mice
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