骨髓增生异常综合征基因突变特征的临床分析

Clinical analysis of gene mutation characteristic in myelodysplastic syndrome

目的探索骨髓增生异常综合征(MDS)患者的基因突变特征及与临床特征的关系。方法分析43例进行二代测序检测的MDS患者的临床资料,分析基因突变特征、基因关联性及其与患者临床特征的关系。结果43例患者中,40例(93.02%)患者检测到基因突变,涉及突变基因33个,29例(67.44%)患者存在基因间伴随突变。表观遗传基因组患者基因突变个数明显多于非表观遗传基因组,差异有统计学意义(P=0.003)。剪接子相关基因U2小核RNA辅助因子1(U2AF1)为本研究检出率最高的突变基因,U2AF1突变组患者基因突变个数多于非突变组,差异有统计学意义(P=0.022)。不同亚型MDS患者基因突变个数存在差异,MDS-U型基因突变个数最多。高危+极高危组MDS患者基因突变个数和染色体异常数目均多于低危+中危组患者,NRAS突变率高于低危+中危组患者,差异均有统计学意义(P﹤0.05)。SET结合蛋白1(SETBP1)突变均发生在异常核型患者中。年龄≥70岁MDS患者剪接因子3b亚基1(SF3B1)突变率高于﹤70岁患者,差异有统计学意义(P=0.011)。结论MDS相关基因突变特征可能与疾病亚型、国际预后积分系统-修订版(IPSS-R)预后分层、染色体核型和患者年龄等临床特征有关。

Objective To explore the gene mutation characteristics in patients with myelodysplastic syndrome(MDS)and its relationship with clinical characteristics.Method The clinical data of 43 MDS patients who accepted next-generation sequencing(NGS)was retrospectively analyzed,the gene mutation characteristics,gene association and the relationship with clinical characteristics of patients were analyzed.Result A total of 40(93.02%)cases had gene mutations,involving 33 mutant genes,and 29(67.44%)cases had intergenic concomitant mutation in 43 patients.The number of mutations in epigenetic genomes was significantly higher than that in non-epigenetic genomes(P=0.003);the splicing-related gene U2 small nuclear RNA auxiliary factor 1(U2AF1)was the mutant gene with the highest detection rate in this study and the number of mutations in the U2AF1 mutant group was more than that in the non-mutant group(P=0.022).There was difference in the number of gene mutations in patients with different subtypes of MDS,and the subtype of MDS-U had the largest number of gene mutations.The number of gene mutations and chromosome abnormalities in MDS patients in high-risk+extremely high-risk group were higher than those in low-risk+medium-risk group,and the mutation rate of NRAS was higher than that in low-risk+medium-risk group(P<0.05).Compared with the normal karyotype,SET binding protein 1(SETBP1)mutation occurred in patients with abnormal karyotype.The mutation rate of splicing factor 3b subunit 1(SF3B1)in MDS patients≥70 years was higher than that in patients<70 years(P=0.011).Conclusion The mutation characteristics of MDS related genes may be closely related to disease subtype,international prognostic score systemrevision(IPSS-R),chromosome karyotype,and patient age.