Identification of the transforming EML4–ALK fusion gene in non-small-cell lung cancer
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- 11 July 2007
- journal article
- research article
- Published by Springer Nature in Nature
- Vol. 448 (7153) , 561-566
- https://doi.org/10.1038/nature05945
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.Keywords
This publication has 26 references indexed in Scilit:
- Transforming activity of purinergic receptor P2Y, G-protein coupled, 2 revealed by retroviral expression screeningBiochemical and Biophysical Research Communications, 2007
- Identification of NVP-TAE684, a potent, selective, and efficacious inhibitor of NPM-ALKProceedings of the National Academy of Sciences, 2007
- Human EML4, a novel member of the EMAP family, is essential for microtubule formationExperimental Cell Research, 2006
- Transforming activity of the lymphotoxin-β receptor revealed by expression screeningBiochemical and Biophysical Research Communications, 2005
- Unique Substrate Specificity of Anaplastic Lymphoma Kinase (ALK): Development of Phosphoacceptor Peptides for the Assay of ALK ActivityBiochemistry, 2005
- EGF receptor gene mutations are common in lung cancers from “never smokers” and are associated with sensitivity of tumors to gefitinib and erlotinibProceedings of the National Academy of Sciences, 2004
- EGFR Mutations in Lung Cancer: Correlation with Clinical Response to Gefitinib TherapyScience, 2004
- Activating Mutations in the Epidermal Growth Factor Receptor Underlying Responsiveness of Non–Small-Cell Lung Cancer to GefitinibNew England Journal of Medicine, 2004
- Sak Serine-Threonine Kinase Acts as an Effector of Tec Tyrosine KinasePublished by Elsevier ,2001
- IL3-dependent mouse clones that express B-220 surface antigen, contain ig genes in germ-line configuration, and generate B lymphocytes in vivoCell, 1985