驱动基因作为肺癌预防和治疗的靶标(英文)

Driver Genes as Targets for Lung Cancer Prevention and Treatment

下一代测序(next generation sequencing,NGS)已经被广泛用于鉴定导致肺癌最重要的驱动基因。与Sanger测序等传统测序策略相比,NGS具有若干突出优势,包括能测定全基因组、全外显子组或转录组中几乎所有基因的序列,能同时检测如碱基替换(突变)、插入、缺失、拷贝数变种、结构变种、基因融合等等。近几年来,科学家们成功地对肺腺癌、鳞癌和小细胞癌等三种肺癌进行了若干综合性的NGS研究,一方面验证了此前已发现的肺癌驱动基因的重要性,另一方面揭示了一些此前在肺癌中未被深入研究的重要驱动基因。在所研究的大多数肺癌样本中存在这些基因的功能性体细胞基因变异,导致了对肺癌发展具有直接影响的关键信号通路的异常。可以预期,不断被发现了解的新肺癌驱动基因将为发现肺癌预防和治疗最佳靶标提供前所未有的机遇。

Next generation sequencing （NGS） has been widely used in identifying the most important driver genes to lung carcinogenesis. Compared to the traditional sequencing approaches such as Sanger sequencing, NGS has several distinct advantages including the capacity to fully sequence almost all of the genes in the whole genome, whole exome or whole transcriptome, and the ability to simultaneously detect all types of genetic variants such as base substitutions （mutations）, insertions, deletions, copy number variants, structural variants, gene fusions, etc. In the past few years, several comprehensive NGS studies on three major types of lung cancer （lung adenocarcinoma, squamous cell lung cancer, and small-cell lung cancer） have been successfully conducted which both confirmed the significance of the previously identified lung cancer driver genes and revealed the ＇novel＇ significant driver genes that were not well known in the lung cancer context before. Functional somatic genetic alterations in these genes exist in the majority of the lung cancer samples studied and altered the critical pathways whose aberrations have a direct impact on lung cancer development. It is anticipated that the expanding list of lung cancer driver genes will provide unprecedented opportunities to identify the best targets for lung cancer prevention and treatment.