初诊急性髓系白血病患者十种常见突变基因的突变组分析

Mutaome analysis including 10 common mutated genes in newly diagnosed acute myeloid leukemia patients

目的 探讨初诊急性髓系白血病（AML）患者中最常见的10种突变基因的突变组合规律.方法 选取AML患者129例,基因测序法检测初诊时骨髓样本中ASXL1、CEBPA、DNMT3A、FLT3、IDH1/2、KIT、NPM1、PHF6和TET2基因突变.结果 68.99％（89/129）患者上述基因突变阳性,30.23％（39/129）同时有多种基因突变.激酶类基因FLT3和KIT突变互斥,不同时出现.FLT多与其他基因伴随突变,而KIT突变多单独出现.转录因子基因CEBPA、NPM1和PHF6可相互伴随突变.表观遗传调控基因ASXL1、DNMT3A、IDH1/2和TET2的突变多与上述两组基因突变同时出现,但该组基因之间较少伴随突变.结论 首次对初诊AML中的突变组按基因的功能和分类进行谱型分析,显示基因突变的组合具有一定的规律,与基因的功能和分类相关.

Objective To investigate the mutaome profile of the 10 common mutated genes in newly diagnosed acute myeloid leukemia （AML） patients.Methods Gene mutations of ASXL1,CEBPA,DNMT3A,FLT3,IDH1/2,KIT,NPM1,PHF6 and TET2 were analyzed using Sanger sequencing method in bone marrow samples of 129 newly diagnosed AML patients.Results 68.99 % （89/129） patients carried at least one mutation,and 30.23 % （39/129） carried multiple mutations.Mutations of kinase gene FLT3 and KIT were mutually exclusive,and FLT3 mutations occured more often with other mutations,while KIT mutations usually occured alone.Mutations of transcription factor genes CEBPA,NPM1 and PHF6 were accompany with each other.Mutations of epigenetic regulation genes ASXL1,DNMT3A,IDH1/2 and TET2 were mutually exclusive,but were accompany with mutations of kinase or transcription factor genes.Conclusions There are certain rules in the appearance of genetic mutations,and which are related to the function and classification of genes.