WT1基因在髓系肿瘤中的变异特点分析  

Analysis of the mutation characteristics of WT1 in myeloid neoplasms

作　　者：马强[1] 刘艳[1] 刘聪艳[1] 赵弘[1] 常晓丽 邹东梅 孙婉玲[1] 胡蓉华[1] MA Qiang;LIU Yan;LIU Congyan;ZHAO Hong;CHANG Xiaoli;ZOU Dongmei;SUN Wanling;HU Ronghua(Department of Hematology,Xuanwu Hospital,Capital Medical University,Beijing 100053,China)

机构地区：[1]首都医科大学宣武医院血液内科,北京100053

出　　处：《现代肿瘤医学》2024年第12期2250-2255,共6页Journal of Modern Oncology

基　　金：首都卫生发展科研专项(编号:2022-2-2019)。

摘　　要：目的:探讨Wilms瘤基因1(WT1)在髓系肿瘤中的变异特点。方法:回顾性分析2017年12月至2023年9月间在我院就诊、接受髓系肿瘤相关基因高通量测序且存在WT1基因变异患者的临床资料,包括人口学资料、疾病类型、基因变异类型、位点及变异等位基因频率(VAF)等,并结合数据库分析WT1变异与急性髓系白血病(AML)和骨髓增生异常综合征(MDS)患者预后间的关系。结果:27例携带WT1基因变异的患者中,20例为初诊检出,7例为治疗监测过程中检出;19例患者为AML(70.37%),其中5例急性早幼粒细胞白血病(APL),14例非APL(11例为AML-M2);4例骨髓增殖性肿瘤(MPN)(14.81%),3例MDS(11.11%)和1例慢性粒单核细胞白血病(CMML)(3.70%);27例患者中共检出可报告变异位点33个,其中截断突变16个(48.48%)(含11个移码突变和5个无义突变)、剪接突变4个(12.12%)、错义突变11个(33.33%)、缺失变异1个(3.03%)、起始密码子突变1个(3.03%);27例患者均伴有其他基因异常,以CEBPA bZIP区突变及PML∶∶RARA融合基因最常见;携带WT1变异的AML患者具有更短的总生存期(OS)(中位OS 11.21月vs 19.10月,P=0.003),但WT1是否发生变异与MDS患者总生存期和无白血病生存期无明显相关性(P>0.05),且WT1表达水平高低与AML患者总生存期间无明显相关性(P>0.05)。结论:WT1基因变异在髓系肿瘤中多见于AML,在AML-M2及APL中发生率最高,变异主要发生于exon 7、1和9,以截断突变为主,几乎都存在其他伴随突变或融合基因。携带WT1突变的AML患者可能具有更短的OS。Objective:To explore the mutation characteristics of Wilms'tumor 1(WT1)in myeloid neoplasms.Methods:A retrospective analysis was conducted on clinical data of patients who received next-generation sequencing of myeloid neoplasms related genes and had WT1 mutations from December 2017 to September 2023 in our hospital,including demographic data,disease type,variation information and variant allele frequency(VAF),etc.,and the relationship between WT1 variation and the prognosis of acute myeloid leukemia(AML)and myelodysplastic syndrome(MDS)was analyzed through database analysis.Results:Among the 27 patients carrying the WT1 mutation,20 patients were detected at initial diagnosis and 7 patients were detected during treatment monitoring.19 patients had AML(70.37%),including 5 cases of acute promyelocytic leukemia(APL)and 14 cases of non-APL(11 cases of AML-M2).There were 4 cases of myeloproliferative neoplasm(MPN)(14.81%),3 cases of MDS(11.11%),and 1 case of chronic myelomonocytic leukemia(CMML)(3.70%).A total of 33 reportable mutation sites were detected in 27 patients,including 16 truncation mutations(48.48%)(including 11 frameshift mutations and 5 nonsense mutations),4 splicing mutations(12.12%),11 missense mutations(33.33%),1 deletion mutation(3.03%),and 1 start codon mutation(3.03%).All 27 patients were accompanied by other genetic abnormalities,with CEBPA bZIP region mutations and PML∶∶RARA fusion genes being the most common.AML patients carrying WT1 mutation had a shorter overall survival(OS)(median OS 11.21 months vs 19.10 months,P=0.003),but there was no significant correlation between WT1 mutation and overall survival or leukemia free survival in MDS patients(P>0.05),and the expression level of WT1 was not significantly correlated with the OS of AML(P>0.05).Conclusion:WT1 mutations are more common in AML in myeloid neoplasms,with the highest incidence in AML-M2 and APL.The mutations mainly occur in exon 7,1,and 9,with truncation mutations being the main type,and almost all other accompanying mutations or

关 键 词：WT1基因 髓系肿瘤 截断突变 AML-M2 

分 类 号：R733[医药卫生—肿瘤]