PMID- 33626444
OWN - NLM
STAT- MEDLINE
DCOM- 20210617
LR  - 20220531
IS  - 1873-264X (Electronic)
IS  - 0731-7085 (Linking)
VI  - 197
DP  - 2021 Apr 15
TI  - Sensitive quantitation of ESR1 mutations in cell-free DNA from breast cancer 
      patients using base-specific invasive reaction assisted qPCR.
PG  - 113959
LID - S0731-7085(21)00071-6 [pii]
LID - 10.1016/j.jpba.2021.113959 [doi]
AB  - Acquired estrogen receptor 1 (ESR1) mutation is being promoted as a key mechanism 
      of resistance to endocrine therapies in breast cancers. It is significative to 
      monitor ESR1 mutations in real time, which provide an opportunity to alter 
      therapy as these mutations emerge. Previous assays based on next-generation 
      sequencing (NGS) and digital PCR (dPCR) usually due to high costs and complicated 
      workflows hampered their clinical adoption in general medical institutions. Here, 
      we proposed a new strategy using base-specific invasive reaction assisted qPCR 
      measure for ESR1 mutations in cfDNA. Two pivotal steps involved in this strategy 
      are target-specific signal generation and the quantification without adding any 
      internal reference or making standard calibration curves. The strategy enabled a 
      high specificity of 0.1% (better than traditional NGS-based method) and a minimum 
      sensitivity of 0.1 copies muL(-1). As validation, with the strategy, cfDNA from 
      endocrine therapy-resistant breast cancers and untreated ones were successfully 
      analyzed (20% mutation rate (2/10) with mutation abundance of 0.54-1.65% vs. 0% 
      mutation rate (0/5)). By virtue of cost-effective, highly flexible and precise, 
      the strategy could be readily implemented in general laboratory, showing 
      promising application perspectives in analysis of other types of mutations.
CI  - Copyright (c) 2021 Elsevier B.V. All rights reserved.
FAU - Wang, Chen
AU  - Wang C
AD  - Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of 
      Education, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, 
      China.
FAU - Zeng, Huijuan
AU  - Zeng H
AD  - Breast Disease Center, The First Affiliated Hospital of SunYat-sen University, 
      Guangzhou 510080, China; Laboratory of Surgery, The First Affiliated Hospital of 
      SunYat-Sen University, Guangzhou 510080, China.
FAU - Zhang, Luning
AU  - Zhang L
AD  - Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of 
      Education, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, 
      China.
FAU - Shen, Yiyun
AU  - Shen Y
AD  - Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of 
      Education, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, 
      China.
FAU - Zou, Bingjie
AU  - Zou B
AD  - Department of Clinical Pharmacy, Jinling Hospital, State Key Laboratory of 
      Analytical Chemistry for Life Science & Jiangsu Key Laboratory of Molecular 
      Medicine, Medical School of Nanjing University, Nanjing 210002, China.
FAU - Wang, Shaohua
AU  - Wang S
AD  - Department of General Surgery, Jinling Hospital, Medical School of Nanjing 
      University, Nanjing 210002, China. Electronic address: wanglaifu2@126.com.
FAU - Song, Qinxin
AU  - Song Q
AD  - Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of 
      Education, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, 
      China. Electronic address: songqinxin@cpu.edu.cn.
FAU - Zhou, Guohua
AU  - Zhou G
AD  - Department of Clinical Pharmacy, Jinling Hospital, State Key Laboratory of 
      Analytical Chemistry for Life Science & Jiangsu Key Laboratory of Molecular 
      Medicine, Medical School of Nanjing University, Nanjing 210002, China; The First 
      School of Clinical Medicine, Southern Medical University, Guangzhou 510515, 
      China.
LA  - eng
PT  - Journal Article
DEP - 20210211
PL  - England
TA  - J Pharm Biomed Anal
JT  - Journal of pharmaceutical and biomedical analysis
JID - 8309336
RN  - 0 (Cell-Free Nucleic Acids)
RN  - 0 (ESR1 protein, human)
RN  - 0 (Estrogen Receptor alpha)
SB  - IM
MH  - *Breast Neoplasms/drug therapy/genetics
MH  - *Cell-Free Nucleic Acids/genetics
MH  - Estrogen Receptor alpha/genetics
MH  - Female
MH  - Humans
MH  - Mutation
MH  - Real-Time Polymerase Chain Reaction
OTO - NOTNLM
OT  - Breast cancer
OT  - ESR1 mutation
OT  - Endocrine therapy
OT  - Resistance
OT  - cfDNA
COIS- Declaration of Competing Interest The authors report no declarations of interest.
EDAT- 2021/02/25 06:00
MHDA- 2021/06/22 06:00
CRDT- 2021/02/24 20:07
PHST- 2020/06/14 00:00 [received]
PHST- 2020/12/30 00:00 [revised]
PHST- 2021/02/04 00:00 [accepted]
PHST- 2021/02/25 06:00 [pubmed]
PHST- 2021/06/22 06:00 [medline]
PHST- 2021/02/24 20:07 [entrez]
AID - S0731-7085(21)00071-6 [pii]
AID - 10.1016/j.jpba.2021.113959 [doi]
PST - ppublish
SO  - J Pharm Biomed Anal. 2021 Apr 15;197:113959. doi: 10.1016/j.jpba.2021.113959. 
      Epub 2021 Feb 11.