靶向测序在疑诊髓系肿瘤患者中的临床应用  

Significance of Targeted Sequencing Assay for Patients with Suspected Myeloid Malignancies

作　　者：张丽娟[1] 史玉叶[1] 陈月[1] 邓媛[1] 丁亦含 李赞[1] 陈侃侃[1] 丁邦和[1] 王春玲[1] 于亮[1] 何正梅[1] ZHANG Li-Juan;SHI Yu-Ye;CHEN Yue;DENG Yuan;DING Yi-Han;LI Zan;CHEN Kan-Kan;DING Bang-He;WANG Chun-Ling;YU Liang;HE Zheng-Mei(Department of Hematology,The Affiliated Huai′an No.1 People′s Hospital of Nanjing Medical University,Key Laboratory of Hematology of Nanjing Medical University,Huai′an 223300,Jiangsu Province,China)

机构地区：[1]南京医科大学附属淮安第一医院血液科,南京医科大学血液研究重点实验室,江苏淮安223300

出　　处：《中国实验血液学杂志》2020年第6期1985-1990,共6页Journal of Experimental Hematology

基　　金：2017年度淮安市第二期“533英才工程”科研资助立项项目(HAA201739);江苏省卫生健康委科研课题(H2018085)。

摘　　要：目的:探讨靶向基因测序在疑似髓系肿瘤患者中的临床意义。方法:对南京医科大学附属淮安第一医院血液科自2018年1月至2019年4月收治的39例疑似髓系肿瘤的血细胞减少患者进行骨髓增生异常综合征(MDS)常见的20个热点基因测序。结果:39例患者包括7例意义未明特发性血细胞减少症(ICUS),8例意义未明克隆性血细胞减少症(CCUS)和24例髓系肿瘤患者(MDS 18例,MDS/MPN 4例,急性髓系白血病2例)。70.8%(17/24)髓系肿瘤患者基因突变阳性;72.7%(16/22)MDS及MDS/MPN患者突变阳性。突变类型以ASXL1、TET2和RUNX1为主,与基因阴性组对比,两组之间的性别、年龄(<60岁或≥60岁)、骨髓原始细胞比例(<5%或≥5%)、细胞遗传学(好、中、差)均无显著统计学差异(P>0.05)。8例CCUS患者均为基因突变阳性,然而双突变或多突变的发生率较MDS及MDS/MPN患者显著降低(37.5%vs 54.5%)(P=0.002)。两组的基因突变类型相似,变异等位基因频率无统计学差异(P>0.05)。结论:靶向测序提示髓系肿瘤患者基因双突变或多突变的比例较高,尤其是MDS及MDS/MPN患者。靶向测序可以提高髓系肿瘤的诊断水平,指导临床治疗。Objective:To investigate the clinical significance of the targeted next-generation sequencing assay for patients with suspected myeloid malignancies.Methods:A total of 39 hematopenia patients with suspected myeloid malignamies in Department of Hematology of The Affiliated Huai′an No.1 People′s Hospital of Nanjing Medical University from January 2018 to April 2019 were treated,20 hot spot genes of myelodysplastic syndrome(MDS)were detected.Results:Regarding the diagnostic type,there were 7 cases of idiopathic cytopenia of undetermined significance(ICUS),8 cases of clonal cytopenias of undetermined significance(CCUS)and 24 cases of myeloid myeloid malignancies which included 18 cases of MDS,4 cases of myelodysplastic/myeloproliferative neoplasms(MDS/MPN)and 2 cases of acute myeloid leukemia.Positive mutation was detected in 70.8%(17/24)of myeloid malignancy patients,and 72.7%(16/22)in MDS and MDS/MPN patients.The main mutation types were ASXL1,TET2 and RUNX1.Compared with gene negative group,there were no significant differences in sex,age(<60 years old or≥60 years old),proportion of bone marrow blast cells(<5%or≥5%)and cytogenetics(good,medium and poor)(P>0.05).Furthermore,all 8 CCUS patients showed positive mutation,and the incidence of double or multiple mutation in CCUS group was significantly lower than that of the MDS and MDS/MPN group(37.5%vs 54.5%)(P=0.002).The mutation types between the two groups were similar,and there was no significant difference in variant allele frequency(P>0.05).Conclusion:Our results suggest that there are high rates of double or multiple mutations in myeloid malignancies,especially in patients with MDS and MDS/MPN.Targeted sequencing assay can improve the diagnosis of myeloid malignancies,and guide clinical treatment.

关 键 词：髓系肿瘤 骨髓增生异常综合征 意义未明克隆性血细胞减少症 靶向测序 突变率 

分 类 号：R733[医药卫生—肿瘤]