1. Division of Functional Genomics,
2. Division of Pulmonary Medicine,
3. Department of Pathology, and,
4. Division of General Thoracic Surgery, Jichi Medical University, Tochigi 329-0498, Japan
5. Research Center for Advanced Science and Technology, University of Tokyo, Tokyo 153-8904, Japan
6. Department of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan
7. Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency, Saitama 332-0012, Japan

Correspondence to: Hiroyuki Mano^1,7 Correspondence and requests for materials should be addressed to H.M. (Email: hmano@jichi.ac.jp).

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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