中国人群中16个已知肺癌基因突变的综合性分析

Comprehensive Mutation Analysis of 16 Known Lung Cancer Genes in Chinese Patients

目的:对过去已知的肺癌基因在中国人群中的突变分布进行综合性的分析,指导肺癌的临床治疗。方法:通过文献查阅,挑选出16个已知的肺癌基因。在112例肺癌样本中,对这16个基因进行大样本的靶基因测序并用Sanger测序来验证。同时,对突变在不同亚组中的分布差异进行分析。结果:16个已知肺癌基因突变可评价60.4%肺癌样本。同时,这些基因的在不同的样本亚组中表现出不同的突变特点;通过功能域的分析及蛋白空间结构的模拟,发现9个可能的突变热点既位于蛋白的功能域内又能导致蛋白空间结构或者表面电荷分布的异常。结论:通过靶基因深度测序,全面分析了16个已知肺癌基因在肺癌不同亚组中的突变分布差异,发现并初步验证了9个可能的肺癌突变热点。

Objective： To direct clinical targeted therapies effectively, comprehensive analysis of mutation profiles for known lung cancer genes were performed in Chinese patients. Methods： 16 known lung cancer genes previously reported were selected., then were examined by targeted gene sequencing and verified by Sanger sequencing in 112 lung cancer samples. In addition, somatic alterations in different subgroups was investigated. Results： Aberrations in 16 known lung cancer genes occurred in 60.4 % of cases. Mutation profiles of 16 known lung cancer genes are distinct in different subgroups; Through the analysis of protein structure domains and crystal structure modeling, 9 putative mutation hotspots were found to be located in protein structure domains and can cause abnormal alterations of electrostatic-charge distribution and crystal structure. Conclusions： By targeted genes deep sequencing, we performed comprehensive analysis for distinct mutation features of 16 known lung cancer genetic alterations in different subgroups. Meanwhile, 9 putative mutation hotspots were discovered and preliminarily validated.