日前,，韓國的研究人員在新一期Genome Research期刊上發(fā)表論文"Fusion of KIF5B and RET transforming gene in lung adenocarcinoma revealed from whole-genome and transcriptome sequencing",，稱發(fā)現(xiàn)了未知的基因融合用于解釋非吸煙者占到肺癌患者的很大比重，這一發(fā)現(xiàn)提供了新療法的靶點(diǎn),。
利用基因組測序和RNA測序,，研究小組特征化地描述了之前未知的基因融合事件，研究的案例是,， 33歲大的韓國男性患有肺癌卻沒有吸煙史和家族遺傳史,。參與研究的科學(xué)家分別來自Macrogen公司,、醫(yī)用基因組研究所-首爾國立大學(xué)、首爾圣母醫(yī)院,、首爾國立大學(xué)醫(yī)學(xué)院和Psoma Therapeutics公司,。
Jeong-Sun Seo 博士是醫(yī)用基因組研究所-首爾國立大學(xué)的負(fù)責(zé)人、Macrogen公司的主席以及該研究的資深作者,，他說：“基因組測序技術(shù)能夠解釋之前隱藏的人類癌癥的病因,，個(gè)性化的癌癥治療可依此作為醫(yī)用靶點(diǎn)。”
測序后,，研究小組比較了病人血液中癌細(xì)胞和正常細(xì)胞的基因組,，在已知的癌癥相關(guān)基因（如，EGFR,、KRAS和EML4-ALK）中沒有發(fā)現(xiàn)突變,，通常這些基因的突變可解釋這一病例。進(jìn)一步研究發(fā)現(xiàn),，癌細(xì)胞中提取的RNA測序后能揭示基因重排事件,，這一現(xiàn)象很可能是腫瘤發(fā)生的誘導(dǎo)因子，而在基因組測序時(shí)很難被發(fā)現(xiàn),。
從RNA序列分析中,，研究人員建立了一系列的候補(bǔ)基因融合事件，并把誘癌因子歸結(jié)為單一事件,，即KIF5B 和RET融合,，10號染色體上出現(xiàn)該基因的反轉(zhuǎn)。這一融合事件之所以令人感興趣,，是因?yàn)橹暗难芯刻岬搅薘ET基因與其它基因的融合是甲狀腺癌癥的誘因,，盡管它在肺中表達(dá)水平低，但是在病人身上高表達(dá),。此外,，KIF5B的蛋白結(jié)構(gòu)域在啟動基因融合事件中不可或缺。
作者提到KIF5B-RET融合出現(xiàn)在大約6%的肺癌患者身上,，這一概率值需要進(jìn)一步驗(yàn)證,，研究人員希望該融合基因能成為醫(yī)療的分子靶點(diǎn)。（生物谷Bioon.com）
doi:10.1101/gr.133645.111
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Fusion of KIF5B and RET transforming gene in lung adenocarcinoma revealed from whole-genome and transcriptome sequencing
Young Seok Ju,Won-Chul Lee,Jong-Yeon Shin,Seungbok Lee,Jeong-Sun Seo
Identification of the molecular events which drive cancer transformation is essential to the development of targeted agents which improve the clinical outcome of lung cancer. Many studies have reported genomic driver mutations in non-small cell lung cancers (NSCLC) over the past decade, however, the molecular pathogenesis of more than 40% of NSCLC is still unknown. To identify new molecular targets in NSCLC, we performed the combined analysis of massively parallel whole-genome and transcriptome sequencing for cancer and paired normal tissue of a 33-year-old lung adenocarcinoma patient, who is a never-smoker and has no familial cancer history. The cancer showed no known driver mutation in EGFR or KRAS and no EML4-ALK fusion. Here we report a novel fusion gene between KIF5B and RET proto-oncogene caused by a pericentric inversion of 10p11.22-q11.21. This fusion gene overexpresses chimeric RET receptor tyrosine kinase, which could spontaneously induce cellular transformation. We identified the KIF5B-RET fusion in two more cases out of twenty primary lung adenocarcinomas in the replication study. Our data demonstrate that a subset of NSCLC could be caused by a fusion of KIF5B and RET, and suggest the chimeric oncogene as a promising molecular target for the personalized diagnosis and treatment of lung cancer.
