摘要
目的 探讨较低危组和较高危组骨髓增生异常综合征(MDS)患者基因突变及基因突变功能组的差异.方法 回顾性病例系列研究.回顾性分析2018年1月至2023年8月就诊于东南大学附属中大医院227例MDS患者的临床资料.根据修订版国际预后积分系统(IPSS-R),将MDS患者分为较低危组(IPSS-R评分≤3.5分)96例与较高危组(IPSS-R评分＞3.5分)131例.采用二代测序检测骨髓标本中58个MDS常见基因突变,取基因突变结果中突变率较高的24个基因纳入研究,并根据基因功能将24个突变基因分为8类.比较较低危组与较高危组临床资料、基因突变及基因突变功能组的差异.结果 227例MDS患者中至少检测出1种基因突变的患者为177例(78.0％),其中突变率较高的5种基因依次为 ASXL1[21.6％(49/227)]、TET2[18.5％(42/227)]、TP53[15.4％(35/227)]、DNMT3A[13.2％(30/227)]、U2AF1[10.1％(23/227)].按基因功能分类,最常见突变组为甲基化相关基因[31.3％(71/227)],其次为剪接体相关基因[24.7％(56/227)].较低危组血小板计数、中性粒细胞计数均高于较高危组,骨髓原始细胞比例、基因突变率及存在≥3种基因突变率均低于较高危组(均P＜0.05).较低危组中突变率较高的 5 种基因依次为 TET2[21.9％(21/96)]、DNMT3A[14.6％(14/96)]、ASXL1[13.5％(13/96)]、SF3B1[12.5％(12/96)]、U2AF1[8.3％(8/96)],较高危组中突变率较高的5种基因依次为 ASXL1[27.5％(36/131)]、TP53[23.7％(31/131)]、TET2[16.0％(21/131)]、DNMT3A[12.2％(16/131)]、U2AF1[11.5％(15/131)],较低危组 ASXL1、TP53、ETV6、NRAS基因突变率均低于较高危组(均P＜0.05).较低危组及较高危组中甲基化相关基因突变比例均最高,但两组比较差异无统计学意义[32.3％(31/96)比30.5％(40/131),x2=0.08,P＞0.05];两组肿瘤因子抑制物相关基因突变、转录因子相关基因突变、染色质修饰相关基因与RAS途径相关基因突变比例比较,差异均有统计学意义(均P＜0.05).结论 较高危组较较低危组MDS患者常见基因突变率高,且基因突变数量多.
Abstract
Objective To investigate the differences in gene mutations and functional clusters of gene mutations in patients with myelodysplastic syndromes(MDS)in the lower-risk and higher-risk groups.Methods A retrospective case series study was conducted.Clinical data of 227 patients with MDS in Zhongda Hospital of Southeast University from January 2018 to August 2023 were retrospectively analyzed.According to the Revised International Prognostic Scoring System(IPSS-R),MDS patients were categorized into the lower-risk group(IPSS-R score ≤3.5 points,96 cases)and the higher-risk group(IPSS-R score＞3.5 points,131 cases).Bone marrow specimens were tested for mutations of 58 common MDS genes using next-generation sequencing,and the 24 genes with the high mutation rates were included in the study,and the 24 mutated genes were categorized into 8 clusters according to gene function.The differences in clinical data,gene mutations and gene mutation functional clusters were compared between the lower-risk group and the higher-risk group.Results At least 1 gene mutation was detected in 177(78.0％)of 227 MDS patients,of which the 5 genes with high mutation rates were ASXL1[21.6％(49/227)],TET2[18.5％(42/227)],TP53[15.4％(35/227)],DNMT3A[13.2％(30/227)],and U2AF1[10.1％(23/227)]in turn.By gene function analysis,the most common mutation cluster was methylation-related genes[31.3％(71/227)],followed by spliceosome-related genes[24.7％(56/227)].Platelet count and neutrophil count in the lower-risk group were higher than those in the higher-risk group,and the proportion of bone marrow primitive cells,the mutation rate and the presence of ≥3 mutations were lower than those in the higher-risk group(all P＜0.05).The 5 genes with high mutation rates in the lower-risk group were TET2[21.9％(21/96)],DNMT3A[14.6％(14/96)],ASXL1[13.5％(13/96)],SF3B1[12.5％(12/96)],and U2AF1[8.3％(8/96)]in turn.The 5 genes with high mutation rates in the higher-risk group were ASXL1[27.5％(36/131)],TP53[23.7％(31/131)],TET2[16.0％(21/131)],DNMT3A[12.2％(16/131)],and U2AF1[11.5％(15/131)]in turn,and the mutation rates of ASXL1,TP53,ETV6,and NRAS genes in the lower-risk group were lower than those in the higher-risk group(all P＜0.05).The mutation rate of methylation-related genes was the highest in both the lower-risk group and the higher-risk group,but the difference between the two groups was not statistically significant[32.3％(31/96)vs.30.5％(40/131),x2=0.08,P＞0.05].The differences in the proportions of tumor factor suppressor-related genes,transcription factor-related genes,chromatin-modification-related genes and RAS pathway-related genes mutations between the two groups were all statistically significant(all P＜0.05).Conclusions The higher-risk group has a higher rate of common gene mutations and a greater number of gene mutations than the lower-risk group in MDS patients.
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