生物谷报道：日本自治医科大学的研究人员１２日通过英国《自然》杂志网站报告说，他们发现由两个基因融合而成的一个异常基因可引发肺癌。
报告指出，这所大学的研究人员以一名有吸烟史的６２岁男性为研究对象，从其肺癌细胞中提取了大量基因，然后将这些基因分别植入实验用的正常细胞，观察细胞是否发生癌变。结果，当植入由“ＡＬＫ”基因和“ＥＭＬ４”基因融合而成的一个基因后，正常细胞就会癌变。
研究人员又从７５名在同一所医院接受治疗的肺癌患者肺部提取癌细胞进行分析，并在５名患者体内发现了这个异常的融合基因，其中４名患者有吸烟史。
“ＡＬＫ”基因具有促进细胞增殖作用，“ＥＭＬ４”基因的作用是维持细胞的形状。研究人员推断，这两个基因融合后，源自“ＡＬＫ”基因的片段就会不受限制地发出增殖指令，导致细胞不断增殖，进而癌变。
参加这项研究的间野博行教授说，研究人员推测某些人体在试图修复受损的ＤＮＡ（脱氧核糖核酸）时，错误地融合了上述两个基因，而烟草可能逃脱不了导致ＤＮＡ受损的干系。
研究人员认为，检测与肺癌有关的异常融合基因的方法一旦成熟，就有望更早地发现早期肺癌。如果能安全地抑制这个融合基因的作用，将对防治肺癌产生重要影响。（新华网）
原始出处:
Nature advance online publication 11 July 2007 | doi:10.1038/nature05945; Received 15 February 2007; Accepted 17 May 2007; Published online 11 July 2007
Identification of the transforming EML4–ALK fusion gene in non-small-cell lung cancer
Manabu Soda1,2, Young Lim Choi1, Munehiro Enomoto1,2, Shuji Takada1, Yoshihiro Yamashita1, Shunpei Ishikawa5, Shin-ichiro Fujiwara1, Hideki Watanabe1, Kentaro Kurashina1, Hisashi Hatanaka1, Masashi Bando2, Shoji Ohno2, Yuichi Ishikawa6, Hiroyuki Aburatani5,7, Toshiro Niki3, Yasunori Sohara4, Yukihiko Sugiyama2 & Hiroyuki Mano1,7
Division of Functional Genomics,
Division of Pulmonary Medicine,
Department of Pathology, and,
Division of General Thoracic Surgery, Jichi Medical University, Tochigi 329-0498, Japan
Research Center for Advanced Science and Technology, University of Tokyo, Tokyo 153-8904, Japan
Department of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan
Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency, Saitama 332-0012, Japan
Correspondence to: Hiroyuki Mano1,7 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.
