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中华普通外科学文献(电子版) ›› 2018, Vol. 12 ›› Issue (05) : 301 -305. doi: 10.3877/cma.j.issn.1674-0793.2018.05.004

所属专题: 文献

论著

循环肿瘤DNA监测转移性乳腺癌治疗过程中肿瘤负荷量动态变化的探索性研究
李舜颖1, 方奕超1, 赖宏娜1, 李玉东1, 刘玉洁1,()   
  1. 1. 510120 广州,中山大学孙逸仙纪念医院乳腺肿瘤中心
  • 收稿日期:2018-08-03 出版日期:2018-10-01
  • 通信作者: 刘玉洁
  • 基金资助:
    国家自然科学基金面上项目(81672622); 国家自然科学基金青年项目(81702630)

Circulating tumor DNA in monitoring the dynamic changes of tumor burden during treatment of metastatic breast cancer

Shunying Li1, Yichao Fang1, Hongna Lai1, Yudong Li1, Yujie Liu1,()   

  1. 1. Department of Breast Cancer, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China
  • Received:2018-08-03 Published:2018-10-01
  • Corresponding author: Yujie Liu
  • About author:
    Corresponding author: Liu Yujie, Email:
引用本文:

李舜颖, 方奕超, 赖宏娜, 李玉东, 刘玉洁. 循环肿瘤DNA监测转移性乳腺癌治疗过程中肿瘤负荷量动态变化的探索性研究[J/OL]. 中华普通外科学文献(电子版), 2018, 12(05): 301-305.

Shunying Li, Yichao Fang, Hongna Lai, Yudong Li, Yujie Liu. Circulating tumor DNA in monitoring the dynamic changes of tumor burden during treatment of metastatic breast cancer[J/OL]. Chinese Archives of General Surgery(Electronic Edition), 2018, 12(05): 301-305.

目的

探讨转移性乳腺癌患者在接受治疗过程中利用高通量测序技术进行循环肿瘤DNA(ctDNA)检测的价值。

方法

通过目标区域捕获结合第二代高通量测序技术,对转移性乳腺癌患者在进行治疗期间不同治疗节点的ctDNA进行测序,并与临床影像学指标进行对比。

结果

本研究共纳入5例转移性乳腺癌患者不同时间点的13份血液样本。利用二代高通量测序技术成功在12份(92.3%)样本中检测出ctDNA,联合生物信息学分析出ctDNA在治疗过程中的各个突变克隆的变化趋势。

结论

二代测序技术对检测转移性乳腺癌的突变谱有应用价值,ctDNA的动态变化能有效反映转移性乳腺癌患者在治疗过程中不同时期的肿瘤负荷量变化。

Objective

To explore the utility of circulating tumor DNA (ctDNA) in evaluating tumor burden and tracking the changes of tumor clones in metastatic breast cancer patients.

Methods

High-throughput sequencing and target region capture was applied in our study to analyze ctDNA sequence in different time points from metastatic breast cancer patients and was compared with the imaging indexes.

Results

The study included thirteen blood samples collected from 5 advanced breast cancer patients at different time points. Next generation sequencing detected ctDNA in 12 out of the 13 samples. Bioinformatics revealed the dynamic changes of ctDNA subclones in metastatic breast cancer patients during treatment.

Conclusion

ctDNA assay is applicable in advanced breast cancer patients and ctDNA can effectively reflect the changes of tumor burden.

表1 5例转移性乳腺癌患者的临床病理特征
表2 各个节点的血液样本中检测到的肿瘤特异体突变列表
样本编号 基因 cHGV pHGV 变异频率(%) 是否驱动突变
P001-1 STK11 c.869T>C p.L290P 1.50
P001-1 TP53 c.273G>A p.W91* 1.70
P002-1 MED12 c.2887G>A p.D963N 0.46
P002-1 EPHA2 c.1987G>A p.E663K 0.75
P002-1 KRAS c.35G>T p.G12V 0.85
P002-1 ALK c.1907T>A p.L636H 1.56
P002-1 PIK3CA c.3140A>G p.H1047R 2.01
P002-2 MED12 c.2887G>A p.D963N 0.38
P002-2 ACIN1 c.16C>T p.R6C 0.47
P002-2 EPHA2 c.1987G>A p.E663K 0.55
P002-2 DNMT3A c.1828C>G p.P610A 1.06
P002-2 HIST1H3B c.7C>G p.R3G 1.09
P002-3 EPHA2 c.1987G>A p.E663K 0.31
P002-4 BRD3 c.1515G>C p.E505D 0.26
P002-4 DNMT3A c.1828C>G p.P610A 0.46
P002-4 ACIN1 c.16C>T p.R6C 0.52
P002-4 EPHA2 c.1987G>A p.E663K 0.66
P002-5 EPHA2 c.1987G>A p.E663K 0.37
P002-5 FAT1 c.1750G>A p.V584M 0.54
P003-1 ERBB4 c.50C>T p.A17V 0.60
P003-1 RICTOR c.2353C>T p.H785Y 3.20
P003-1 ESR1 c.1138G>C p.E380Q 3.30
P003-1 RPS6KB1 c.138G>C p.E46D 4.50
P003-2 RPS6KB1 c.138G>C p.E46D 0.60
P004-1 DNMT3A c.2403G>A p.M801I 0.90
P004-1 NOTCH2 c.3554-3561delAGTATGAA p.E1185Gfs*3 1.30
P004-1 TBX3 c.1852G>A p.A618T 1.50
P004-1 DPYD c.1708T>G p.F570V 3.30
P004-1 TP53 c.817C>T p.R273C 11.40
P004-2 KDM5C c.3826G>A p.E1276K 0.90
P005-1 ESR1 c.728G>A p.R243H 0.50
P005-1 ABCC11 c.403C>T p.R135C 0.70
P005-1 CDH18 c.2317G>A p.E773K 0.70
P005-1 PIK3CA c.1035T>A p.N345K 0.90
P005-2 ESR1 c.1609T>A p.Y537N 0.50
P005-2 NF1 c.1819A>G p.R607G 0.50
P005-2 PIK3CA c.1035T>A p.N345K 3.00
图1 5例患者ctDNA中各个突变克隆在治疗过程中的变异频率变化 A、B、C、D、E为患者P001-P005各个治疗节点ctDNA突变基因变异频率的变化
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