生物谷報(bào)道：日本自治醫(yī)科大學(xué)的研究人員１２日通過英國《自然》雜志網(wǎng)站報(bào)告說,，他們發(fā)現(xiàn)由兩個基因融合而成的一個異?；蚩梢l(fā)肺癌。
報(bào)告指出,，這所大學(xué)的研究人員以一名有吸煙史的６２歲男性為研究對象,，從其肺癌細(xì)胞中提取了大量基因,，然后將這些基因分別植入實(shí)驗(yàn)用的正常細(xì)胞，觀察細(xì)胞是否發(fā)生癌變,。結(jié)果,，當(dāng)植入由“ＡＬＫ”基因和“ＥＭＬ４”基因融合而成的一個基因后，正常細(xì)胞就會癌變,。
研究人員又從７５名在同一所醫(yī)院接受治療的肺癌患者肺部提取癌細(xì)胞進(jìn)行分析,，并在５名患者體內(nèi)發(fā)現(xiàn)了這個異常的融合基因，其中４名患者有吸煙史,。
“ＡＬＫ”基因具有促進(jìn)細(xì)胞增殖作用,，“ＥＭＬ４”基因的作用是維持細(xì)胞的形狀。研究人員推斷,，這兩個基因融合后,，源自“ＡＬＫ”基因的片段就會不受限制地發(fā)出增殖指令，導(dǎo)致細(xì)胞不斷增殖,，進(jìn)而癌變,。
參加這項(xiàng)研究的間野博行教授說，研究人員推測某些人體在試圖修復(fù)受損的ＤＮＡ（脫氧核糖核酸）時,，錯誤地融合了上述兩個基因,，而煙草可能逃脫不了導(dǎo)致ＤＮＡ受損的干系。
研究人員認(rèn)為,，檢測與肺癌有關(guān)的異常融合基因的方法一旦成熟,，就有望更早地發(fā)現(xiàn)早期肺癌。如果能安全地抑制這個融合基因的作用,，將對防治肺癌產(chǎn)生重要影響。（新華網(wǎng)）
原始出處:
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: [email protected]).
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.
