[1]苟阳,唐永杰,杨程,等.305例髓系肿瘤的基因突变图谱比较分析[J].第三军医大学学报,2019,41(21):2069-2073.
 GOU Yang,TANG Yongjie,YANG Cheng,et al.Landscape of genetic alterations of myeloid neoplasms in 305 Chinese cases[J].J Third Mil Med Univ,2019,41(21):2069-2073.
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305例髓系肿瘤的基因突变图谱比较分析(/HTML )
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《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
41卷
期数:
2019年第21期
页码:
2069-2073
栏目:
基础医学
出版日期:
2019-11-15

文章信息/Info

Title:
Landscape of genetic alterations of myeloid neoplasms in 305 Chinese cases
作者:
苟阳唐永杰杨程彭贤贵
400037 重庆,陆军军医大学(第三军医大学)第二附属医院血液病医学中心,全军血液病中心,创伤、烧伤与复合伤研究国家重点实验室
Author(s):
GOU Yang TANG Yongjie YANG Cheng PENG Xiangui

State Key Laboratory of Trauma, Burns and Combined Injury, Medical Center of Hematology, PLA Center for Hematology, Second Affiliated Hospital, Army Medical University (Third Military Medical University), Chongqing, 400037, China

关键词:
急性髓系白血病骨髓增生异常综合征骨髓增殖性肿瘤骨髓增生异常综合征/骨髓增殖性肿瘤基因突变二代测序信号通路
Keywords:
acute myeloid leukemia myelodysplastic syndromes myeloproliferative neoplasms myelodysplastic/myeloproliferative neoplasms gene mutation second-generation sequencing signaling pathway
分类号:
Q755; R195.4; R733.7
文献标志码:
A
摘要:

目的比较分析急性髓系白血病(acute myeloid leukemia,AML)、骨髓增生异常综合征(myelodysplastic syndromes,MDS)、骨髓增殖性肿瘤(myeloproliferative neoplasms,MPN)、骨髓增生异常综合征/骨髓增殖性肿瘤(myelodysplastic/myeloproliferative neoplasms,MDS/MPN)患者的基因突变图谱。方法对本院2017年1月至2019年1月就诊的305例髓系肿瘤患者(186例AML,64例MDS,27例MPN,28例MDS/MPN)的骨髓细胞进行髓系肿瘤常见突变基因二代测序检测,绘制基因突变图谱,分析比较各髓系肿瘤基因和基因通路突变比例的差异,及各突变基因突变率的差异。结果305例髓系肿瘤患者共检测到30个基因的606个突变,15.4%未检测到基因突变,58.0%检测到2个及以上基因突变,1人最多有7个基因突变,TET2、DNMT3A、NRAS、CEBPA、JAK2、C-KIT、U2AF1、NPM1等基因的突变比例在多个髓系肿瘤中均较高。信号通路相关基因在AML、MPN和MDS/MPN中的突变比例均>50%,在MDS中<10%;转录因子相关基因在AML中的突变比例>50%,在MPN中<5%;表观遗传学相关基因在4个髓系肿瘤中突变比例均>50%;RNA剪接相关基因在MDS和MDS/MPN中突变比例均>30%,在AML中的突变比例<5%。NRAS、C-KIT等信号通路相关基因突变更倾向于低突变率,TET2、DNMT3A等表观遗传学相关基因突变更倾向于高突变率。结论4个髓系肿瘤的基因突变图谱具有差异性:信号通路相关基因在MDS中突变比例低,转录因子相关基因在MPN中突变比例低,RNA剪接相关基因在MDS相关疾病中突变比例高,表观遗传学相关基因在4个髓系肿瘤中突变比例均高。

Abstract:

ObjectiveTo analyze the landscape of genetic alterations of acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), myeloproliferative neoplasms (MPN), and myelodysplastic/myeloproliferative neoplasms (MDS/MPN). MethodsSecond-generation sequencing for common mutant genes was performed in the bone marrow cells derived from 305 myeloid leukemia patients (including 186 cases of AML, 64 cases of MDS, 27 cases of MPN, and 28 cases of MDS/MPN) treated in our hospital from January 2017 to January 2019. The gene mutation map was drawn. The mutation ratios of the genes and gene pathways of each myeloid tumor and the mutation rate of each mutant gene were compared among the different myeloid neoplasms. ResultsThere were 606 mutations detected among 30 genes in the 305 cases. There were 15.4% cases with 0 mutation and 58.0% with more than 1 mutation. And up to 7 mutations were found in 1 case. Mutations of TET2, DNMT3A, NRAS, CEBPA, JAK2, C-KIT, U2AF1, and NPM1 were most common in the myeloid neoplasms. Mutations of signaling pathway-related genes accounted for over 50% in AML, MPN and MDS/MPN, and less than 10% in MDS. Mutations of transcription factors-related genes covered over 50% in AML, and less than 5% in MPN. Mutations of epigenetics-related gene were over 50% in all myeloid neoplasms. RNA splicing factors were mutated for over 30% in MDS and MDS/MPN, and less than 5% in AML. Mutations in signaling pathway-related genes such as NRAS and C-KIT were more prone to low mutation rates, and those of epigenetics-related genes such as TET2 and DNMT3A were more prone to high mutation rates. ConclusionThe genetic landscapes are different among AML, MDS, MPN, and MDS/MPN. The mutation ratios of signaling pathway-related genes are quite low in MDS, so are the ratios of transcription factors-related genes in MPN. Meanwhile, the ratios of RNA splicing factors- and epigenetics-related genes are quite high in MDS and MDS/MPN, respectively.
 

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更新日期/Last Update: 2019-11-12