Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies
Open accessAbstract
Applying a next-generation sequencing assay targeting 145 cancer-relevant genes in 40 colorectal cancer and 24 non-small cell lung cancer formalin-fixed paraffin-embedded tissue specimens identified at least one clinically relevant genomic alteration in 59% of the samples and revealed two gene fusions, C2orf44-ALK in a colorectal cancer sample and KIF5B-RET in a lung adenocarcinoma. Further screening of 561 lung adenocarcinomas identified 11 additional tumors with KIF5B-RET gene fusions (2.0%; 95% CI 0.8-3.1%). Cells expressing oncogenic KIF5B-RET are sensitive to multi-kinase inhibitors that inhibit RET.
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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 [14]
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- Authors
- Lipson, D., Capelletti, M., Yelensky, R., Otto, G., Parker, A., Jarosz, M., Curran, J. A., Balasubramanian, S., Bloom, T., Brennan, K. W., Donahue, A., Downing, S. R., Frampton, G. M., Garcia, L., Juhn, F., Mitchell, K. C., White, E., White, J., Zwirko, Z., Peretz, T., Nechushtan, H., Soussan-Gutman, L., Kim, J., Sasaki, H., Kim, H. R., Park, S.-I., Ercan, D., Sheehan, C. E., Ross, J. S., Cronin, M. T., Jänne, P. A., & Stephens, P. J.
- Affiliations
- Foundation Medicine (United States) (US)
- Dana-Farber Cancer Institute (US)
- Hadassah Medical Center (IL)
- Samsung Medical Center (KR)
- Nagoya City University (JP)
- Asan Medical Center (KR)
- Albany Medical Center Hospital (US)
- Corresponding author
- Cronin, Maureen T
- Stephens, Philip J
- ORCID
- Venue
- Nature Medicine
- Published
- 2012-02-12
- Volume
- 18
- Issue
- 3
- Pages
- 382-384
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC3916180
- OpenAlex
- W2018336040
- Cited by
- 869
- References
- 20
- Citations by year
- 2026: 17 · 2025: 27 · 2024: 37 · 2023: 46 · 2022: 42 · 2021: 46 · 2020: 54 · 2019: 37 · 2018: 53 · 2017: 56 · 2016: 73 · 2015: 87 · 2014: 108 · 2013: 126 · 2012: 58
- FWCI
- 97.68
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Japan Society for the Promotion of Science (21591820)
- National Cancer Institute (R01CA136851, P50CA090578)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- ALK fusion, RET fusion, KIF5B-RET fusion, JAK2 mutation, colorectal cancer, non-small cell lung cancer, lung adenocarcinoma, druggable targets, multikinase inhibitor, RET inhibition, targeted next-generation sequencing, formalin-fixed paraffin-embedded tissue
- MeSH terms
- Anaplastic Lymphoma Kinase, Animals, Biopsy, Carcinoma, Non-Small-Cell Lung, Cell Transformation, Neoplastic, Humans, Lung Neoplasms, Colorectal Neoplasms, Oncogene Proteins, Fusion, Gene Expression Regulation, Neoplastic, Kinesins, Receptor Protein-Tyrosine Kinases, NIH 3T3 Cells, Protein Kinase Inhibitors, Proto-Oncogene Proteins c-ret, Mice, High-Throughput Nucleotide Sequencing
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