Identification of the transforming EML4–ALK fusion gene in non-small-cell lung cancer
| Autor: | Toshiro Niki, Shoji Ohno, Yukihiko Sugiyama, Hiroyuki Aburatani, Hideki Watanabe, Masashi Bando, Shunpei Ishikawa, Hiroyuki Mano, Munehiro Enomoto, Shuji Takada, Shin-ichiro Fujiwara, Yuichi Ishikawa, Young Lim Choi, Yasunori Sohara, Kentaro Kurashina, Yoshihiro Yamashita, Hisashi Hatanaka, Manabu Soda |
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| Rok vydání: | 2007 |
| Předmět: |
Lung Neoplasms
EML4/ALK Fusion Gene Oncogene Proteins Fusion medicine.drug_class Molecular Sequence Data Cell Cycle Proteins Biology Fusion gene Mice Carcinoma Non-Small-Cell Lung medicine ROS1 Animals Humans Anaplastic lymphoma kinase Anaplastic Lymphoma Kinase Amino Acid Sequence Cell Proliferation Multidisciplinary Crizotinib Serine Endopeptidases ALK Gene Amplification Receptor Protein-Tyrosine Kinases 3T3 Cells Protein-Tyrosine Kinases respiratory tract diseases ALK inhibitor Cell Transformation Neoplastic Fusion transcript Chromosomes Human Pair 2 Chromosome Inversion Mutation Immunology Cancer research Microtubule-Associated Proteins medicine.drug |
| Zdroj: | Nature. 448:561-566 |
| ISSN: | 1476-4687 0028-0836 |
| DOI: | 10.1038/nature05945 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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