Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer
Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer
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DOI：
10.1038/nature05945
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发表时间：
2007-08-02
期刊：
影响因子：
64.8
通讯作者：
Mano, Hiroyuki
中科院分区：
文献类型：
--
作者：
Soda, Manabu;Choi, Young Lim;Mano, Hiroyuki
肺癌临床结果的改善可能是通过确定其发病机制的分子事件来实现的。本研究表明，在非小细胞肺癌（NSCLC）细胞中，染色体2p内的一个小反转导致了一个融合基因的形成，融合基因包括棘皮微管相关蛋白样4 （EML4）基因和间变性淋巴瘤激酶（ALK）基因的一部分。小鼠3T3成纤维细胞被迫表达这种人融合酪氨酸激酶，在培养物和裸鼠皮下肿瘤中产生转化灶。在接受检查的非小细胞肺癌患者中，6.7%（75例中有5例）检测到EML4-ALK融合转录物；这些个体不同于表皮生长因子受体基因突变的个体。我们的数据表明，一部分非小细胞肺癌患者可能表达一种转化融合激酶，这是一种有希望的治疗靶点和非小细胞肺癌诊断分子标志物。
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.