骨髓增生异常综合征相关基因突变及临床特征分析

Analysis of Gene Mutation and Clinical Characteristics Related to Myelodysplastic Syndrome

目的:探讨骨髓增生异常综合征(MDS)患者基因突变的特点及其与临床特征之间的关系。方法:回顾性分析蚌埠医科大学第一附属医院2017年1月至2021年12月就诊的MDS患者172例,检测MDS相关14种高频突变基因,分析基因突变与患者的临床特征及修订的国际预后积分系统(IPSS-R)等的关系,探讨基因突变对预后的影响。结果:172例患者中男101例,女71例,中位年龄67(15-89)岁,检测到发生突变患者88例(51.2%)。突变发生率>5%的基因由高到低依次为TET2(16.9%)、RUNX1(12.8%)、ASXL1(12.2%)、CEBPA(8.1%)、TP53(7.0%)、DNMT3A(6.4%)。按照生物学功能分类,突变频率最高的为表观遗传学调控基因(36.6%)。基因突变组的骨髓原始细胞比例高于非突变组(P<0.001)。不同MDS亚型的基因突变发生率不同,且各亚型基因突变发生率差异有统计学意义(P<0.05)。IPSS-R较高危组(IPSS-R>3.5分)的基因突变发生率为65.7%,显著高于较低危组(IPSS-R≤3.5分)的30.0%(P<0.05),且TP53基因在两组间的突变发生率差异有统计学意义(P<0.05)。多因素Cox生存分析显示,伴TP53、NPM1及TET2基因突变均是影响患者预后的独立危险因素。结论:MDS患者易发生基因突变,逐渐增加的突变数目和伴TP53、NPM1及TET2基因突变可能是患者预后的影响因素。

Objective:To explore the characteristics of gene mutation in patients with myelodysplastic syndrome(MDS)and its correlation with clinical features.Methods:From January 2017 to December 2021,172 patients with MDS in The First Affiliated Hospital of Bengbu Medical University were analyzed retrospectively.Fourteen high frequency genes related to MDS were detected,and the relationship between gene mutation and clinical characteristics of patients as well as revised International Prognostic Scoring System(IPSS-R)was analyzed.The impact of gene mutations on prognosis was explored.Results:Among 172 patients,there were 101 males and 71 females,with a median age of 67(15-89)years old,and gene mutations were detected in 88 cases(51.2%).The genes with mutation incidence>5%were arranged in descending order as follows:TET2(16.9%),RUNX1(12.8%),ASXL1(12.2%),CEBPA(8.1%),TP53(7.0%)and DNMT3A(6.4%).According to biological functional classification,the genes with the highest mutation frequency were epigenetic regulatory genes(36.6%).The proportion of primitive bone marrow cells in mutation group was higher than that in non-mutation group(P<0.001).The incidence of gene mutation varied in different MDS subtypes,and the difference was statistically significant(P<0.05).The mutation incidence in IPSS-R higher risk group(IPSS-R score>3.5)was 65.7%,which was significantly higher than 30.0%in IPSS-R lower risk group(IPSS-R score≤3.5)(P<0.05),and there was a statistically significant difference in the incidence of TP53 gene mutation between the two groups(P<0.05).Multivariate Cox survival analysis showed that TP53,NPM1 and TET2 gene mutation were independent risk factors affecting prognosis.Conclusion:MDS patients are prone to gene mutation,and the increasing number of mutations and the presence of TP53,NPM1 and TET2 gene mutation may be factors affecting the prognosis.