DNA terminal structure-mediated enzymatic reaction for ultra-sensitive discrimination of single nucleotide variations in circulating cell-free DNA.

Tongbo Wu, Wei Chen, Ziyu Yang, Haocheng Tan, Jiayu Wang, Xianjin Xiao, Mengyuan Li, Meiping Zhao

Abstract read

In one paragraph

Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it

0cells of the map it votes in

9citing papers in PubMed

–field-weighted citation impact

1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed.

Epigenomic modifications define chromatin states to regulate cell-free DNA fragmentomics.Nature communications · 2026
Article
Cancer-Like Fragmentomic Characteristics of Somatic Variants in Cell-Free DNA.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
Article
Bacteriophage λ exonuclease and a 5'-phosphorylated DNA guide allow PAM-independent targeting of double-stranded nucleic acids.Nature biotechnology · 2025
Article
A signal transmission strategy driven by gap-regulated exonuclease hydrolysis for hierarchical molecular networks.Communications biology · 2024
Article
Detection of low-frequency mutations in clinical samples by increasing mutation abundance via the excision of wild-type sequences.Nature biomedical engineering · 2023
Article
PAM-independent ultra-specific activation of CRISPR-Cas12a via sticky-end dsDNA.Nucleic acids research · 2022
Article
SLAM-MS: Mutation scanning of stem-loop amplicons with TaqMan probes by quantitative DNA melting analysis.Scientific reports · 2020
Article
Thermodynamics and kinetics guided probe design for uniformly sensitive and specific DNA hybridization without optimization.Nature communications · 2019
Article
Allele-Specific Isothermal Amplification Method Using Unmodified Self-Stabilizing Competitive Primers.Analytical chemistry · 2018
Article

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Tongbo WuBeijing National Laboratory for Molecular Sciences and MOE Key Laboratory of Bioorganic Chemistry and Molecular Engineering, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.

Wei ChenBeijing National Laboratory for Molecular Sciences and MOE Key Laboratory of Bioorganic Chemistry and Molecular Engineering, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.

Ziyu YangBeijing National Laboratory for Molecular Sciences and MOE Key Laboratory of Bioorganic Chemistry and Molecular Engineering, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.

Haocheng TanBeijing National Laboratory for Molecular Sciences and MOE Key Laboratory of Bioorganic Chemistry and Molecular Engineering, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.

Jiayu WangBeijing National Laboratory for Molecular Sciences and MOE Key Laboratory of Bioorganic Chemistry and Molecular Engineering, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.

Xianjin XiaoFamily Planning Research Institute/Center of Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Mengyuan LiBeijing National Laboratory for Molecular Sciences and MOE Key Laboratory of Bioorganic Chemistry and Molecular Engineering, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.

Meiping ZhaoBeijing National Laboratory for Molecular Sciences and MOE Key Laboratory of Bioorganic Chemistry and Molecular Engineering, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Sensitive detection of the single nucleotide variants in cell-free DNA (cfDNA) may provide great opportunity for minimally invasive diagnosis and prognosis of cancer and other related diseases. Here, we demonstrate a facile new strategy for quantitative measurement of cfDNA mutations at low abundance in the cancer patients' plasma samples. The method takes advantage of a novel property of lambda exonuclease which effectively digests a 5'-fluorophore modified dsDNA with a 2-nt overhang structure and sensitively responds to the presence of mismatched base pairs in the duplex. It achieves a limit of detection as low as 0.02% (percentage of the mutant type) for BRAFV600E mutation, NRASQ61R mutation and three types of EGFR mutations (G719S, T790M and L858R). The method enabled identification of BRAFV600E and EGFRL858R mutations in the plasma of different cancer patients within only 3.5 h. Moreover, the terminal structure-dependent reaction greatly simplifies the probe design and reduces the cost, and the assay only requires a regular real-time PCR machine. This new method may serve as a practical tool for quantitative measurement of low-abundance mutations in clinical samples for providing genetic mutation information with prognostic or therapeutic implications.

Indexed as

ExodeoxyribonucleasesViral ProteinsCirculating Tumor DNADNADNA Mutational AnalysisErbB ReceptorsHumansNeoplasmsProto-Oncogene Proteins B-rafBRAF protein, humanCirculating Tumor DNADNAEGFR protein, humanErbB ReceptorsExodeoxyribonucleasesexo protein, Bacteriophage lambdaProto-Oncogene Proteins B-rafViral Proteins

Identifiers

PMID29190359

DOI10.1093/nar/gkx1218

PMCPMC5829738

What Socratic holds

Textmetadata

LicenceCC BY-NC

Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.