Identification of the transforming EML4–ALK fusion gene in non-small-cell lung cancer
Abstract
Improvement in the clinical outcome of lung cancer is likely to be achieved by identification of the molecular events that underlie its pathogenesis. Here we show that a small inversion within chromosome 2p results in the formation of a fusion gene comprising portions of the echinoderm microtubule-associated protein-like 4 (EML4) gene and the anaplastic lymphoma kinase (ALK) gene in non-small-cell lung cancer (NSCLC) cells. Mouse 3T3 fibroblasts forced to express this human fusion tyrosine kinase generated transformed foci in culture and subcutaneous tumours in nude mice. The EML4-ALK fusion transcript was detected in 6.7% (5 out of 75) of NSCLC patients examined; these individuals were distinct from those harbouring mutations in the epidermal growth factor receptor gene. Our data demonstrate that a subset of NSCLC patients may express a transforming fusion kinase that is a promising candidate for a therapeutic target as well as for a diagnostic molecular marker in NSCLC.
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In that afatinib study, survival was not significantly longer (16.6 v 14.8 months).
“Survival was not significantly longer (16.6 v 14.8 months).”
From Systemic Therapy for Stage IV Non–Small-Cell Lung Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update (2015) · cites this paper as [86]
One study with PFS as primary outcome compared first-line afatinib with cisplatin plus pemetrexed and showed improvement with afatinib (11.1 v 6.9 months; HR, 0.58; 95% CI, 0.43 to 0.78; P = .001).
“One study, with PFS as primary outcome, compared first-line afatinib with cisplatin plus pemetrexed. The results showed improvement with afatinib (11.1 v 6.9 months; HR, 0.58; 95% CI, 0.43 to 0.78; P = .001).”
From Systemic Therapy for Stage IV Non–Small-Cell Lung Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update (2015) · cites this paper as [86]
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- Authors
- Soda, M., Choi, Y. L., Enomoto, M., Takada, S., Yamashita, Y., Ishikawa, S., Fujiwara, S.-I., Watanabe, H., Kurashina, K., Hatanaka, H., Bando, M., Ohno, S., Ishikawa, Y., Aburatani, H., Niki, T., Sohara, Y., Sugiyama, Y., & Mano, H.
- Affiliations
- Jichi Medical University (JP)
- Research Center for Advanced Science and Technology, The University of Tokyo (JP)
- Japanese Foundation For Cancer Research (JP)
- Japan Science and Technology Agency (JP)
- Corresponding author
- Mano, Hiroyuki
- ORCID
- Venue
- Nature
- Published
- 2007-07-11
- Volume
- 448
- Issue
- 7153
- Pages
- 561-566
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2055402151
- Cited by
- 5,439
- References
- 28
- Citations by year
- 2026: 118 · 2025: 185 · 2024: 189 · 2023: 239 · 2022: 257 · 2021: 297 · 2020: 333 · 2019: 340 · 2018: 368 · 2017: 393 · 2016: 409 · 2015: 449 · 2014: 436 · 2013: 403 · 2012: 375
- FWCI
- 106.68
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- 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
- EML4-ALK fusion, non-small cell lung cancer, anaplastic lymphoma kinase, EML4, oncogenic translocation, oncogenes, therapeutic target, EGFR mutation
- MeSH terms
- Anaplastic Lymphoma Kinase, Amino Acid Sequence, Animals, Carcinoma, Non-Small-Cell Lung, Cell Transformation, Neoplastic, Chromosomes, Human, Pair 2, Humans, Chromosome Inversion, Lung Neoplasms, Microtubule-Associated Proteins, Molecular Sequence Data, Mutation, Protein-Tyrosine Kinases, Serine Endopeptidases, Oncogene Proteins, Fusion, 3T3 Cells, Cell Cycle Proteins, Receptor Protein-Tyrosine Kinases, Cell Proliferation, Mice
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