肺癌中致病融合基因的研究进展

Research progress on pathogenic fusion gene in lung cancer

肺癌具有高发病率和高死亡率两个特征,是当今世界范围内危害性最大的疾病之一。致病融合基因是一类特殊的驱动基因,是肺癌发生的一种常见机制。大多数融合基因编码受体酪氨酸激酶,一般由染色体重排所致,是肺癌治疗的潜在靶标。继2007年肺癌中ALK融合基因被发现以来,随着荧光原位杂交技术(FISH)、免疫组化(IHC)、逆转录聚合酶链反应(RT-PCR)和下一代测序(NGS)等方法的广泛应用,在随后的15年中其他的一些致病融合基因也陆续被鉴定,包括ROS1、RET、FGFR、NTRK1、NRG1、DNAH5和LTK。这些发现进一步完善了肺癌的致病基因突变谱,为临床患者的个体化治疗提供了重要的理论依据。目前,针对部分融合基因已开发出相应的激酶抑制剂并且表现出良好的治疗效果,但仍然存在耐药性等问题,因此相应患者的治疗仍旧面临着重重挑战。本文结合近年来相关的文献报道,对肺癌中致病融合基因的研究进展作一综述。

Lung cancer is one of the most harmful global diseases with high morbidity and mortality rate.As a unique kind of driver gene,the pathogenic fusion gene is a common mechanism of lung cancer.Most fusion genes are produced by chromosome rearrangement and encoding receptor tyrosine kinases,which could be potential lung cancer therapeutic targets.Since ALK was first identified in 2007,methods like FISH,IHC,RT-PCR and NGS have been intensively applied,leading to identification of multiple other lung cancer fusion genes including ROS1,RET,FGFR,NTRK1,NRG1,DNAH5 and LTK.These works broaden the spectrum of lung cancer related gene mutations,and support the customized treatment for clinical patients.For some fusion genes,corresponding kinase inhibitors have been developed with good efficacy,however,the treatment is still being challenged by several problems like drug resistance.Based on recent studies,the research development of lung cancer fusion genes will be discussed.