305例髓系肿瘤的基因突变图谱比较分析

苟阳; 唐永杰; 杨程; 彭贤贵

doi:10.16016/j.1000-5404.201906075

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305例髓系肿瘤的基因突变图谱比较分析

基础医学 | 更新时间：2026-01-09

- 305例髓系肿瘤的基因突变图谱比较分析
- Landscape of genetic alterations of myeloid neoplasms in 305 Chinese cases
- 第三军医大学学报 2019年第21期页码：2069-2073
- 作者机构：
  
  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
- 作者简介：
  
  [ 彭贤贵，E-mail:pxg1964@sina.com PENG Xiangui, E-mail:pxg1964@sina.com
- 基金信息：
  
  重庆市社会事业与民生保障科技创新专项(CSTC2017shmsA130003)
- DOI：10.16016/j.1000-5404.201906075
  中图分类号： Q755;R195.4;R733.7
- 收稿：2019-06-13，
  
  修回：2019-07-26，
  
  纸质出版：2019-11-15
- 稿件说明：
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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,(21):2069-2073.

Yang GOU, Yongjie TANG, Cheng YANG, et al. Landscape of genetic alterations of myeloid neoplasms in 305 Chinese cases[J]. Journal of Third Military Medical University, 2019, (21): 2069-2073.
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,(21):2069-2073. DOI： 10.16016/j.1000-5404.201906075.

Yang GOU, Yongjie TANG, Cheng YANG, et al. Landscape of genetic alterations of myeloid neoplasms in 305 Chinese cases[J]. Journal of Third Military Medical University, 2019, (21): 2069-2073. DOI： 10.16016/j.1000-5404.201906075.

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

Objective

To analyze the landscape of genetic alterations of acute myeloid leukemia (AML)

myelodysplastic syndrome (MDS)

myeloproliferative neoplasms (MPN)

and myelodysplastic/myeloproliferative neoplasms (MDS/MPN).

Methods

Second-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.

Results

There 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.

Conclusion

The 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.

关键词

Keywords

references

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