Evidence map›Paper›PMID 30150316›Full record

Trial reportClinical chemistry2018

Ultra-Sensitive Mutation Detection and Genome-Wide DNA Copy Number Reconstruction by Error-Corrected Circulating Tumor DNA Sequencing.

Sonia Mansukhani, Louise J Barber, Dimitrios Kleftogiannis, Sing Yu Moorcraft, Michael Davidson, Andrew Woolston, Paula Zuzanna Proszek, Beatrice Griffiths, Kerry Fenwick, Bram Herman and 20 more

Registry-linked trialOpen access · bronzeAbstract readClinical Trial
In one paragraph

Trial report in Clinical chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02112357 (FOrMAT - Feasibility of a Molecular Characterisation Approach to Treatment), which is not on this map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
3.0field-weighted citation impact, top 8% of its field
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.

NCT02112357 unknown statusnot on this map

FOrMAT - Feasibility of a Molecular Characterisation Approach to Treatment

TypeobservationalSponsorRoyal Marsden NHS Foundation TrustRan2014Enrolled200ConditionsAdvanced Gastrointestinal Cancers
3 · Its place in the literature

Who cites it

32 citing papers in PubMed, 56 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Article
  4. Review of ctDNA in breast cancer - present utility and future perspectives.Reports of practical oncology and radiotherapy : journal of Greatpoland Cancer Center in Poznan and Polish Society of Radiation Oncology · 2026
    Review
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  14. Review
  15. Review
  16. International journal of molecular sciences · 2021
    Article
  17. Article
  18. Feasibility of MethylatedFrontiers in oncology · 2021
    Article
  19. Article
  20. Review
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

30 authors at 6 institutions in 2 countries.

Sonia MansukhaniCentre for Evolution and Cancer, Division of Molecular Pathology, The Institute of Cancer Research, London, UK.
Louise J BarberCentre for Evolution and Cancer, Division of Molecular Pathology, The Institute of Cancer Research, London, UK.
Dimitrios KleftogiannisCentre for Evolution and Cancer, Division of Molecular Pathology, The Institute of Cancer Research, London, UK.
Sing Yu MoorcraftGastrointestinal Cancer Unit, The Royal Marsden NHS Foundation Trust, London and Sutton, UK.
Michael DavidsonGastrointestinal Cancer Unit, The Royal Marsden NHS Foundation Trust, London and Sutton, UK.
Andrew WoolstonCentre for Evolution and Cancer, Division of Molecular Pathology, The Institute of Cancer Research, London, UK.
Paula Zuzanna ProszekCentre for Molecular Pathology, The Royal Marsden NHS Foundation Trust, Sutton, UK.
Beatrice GriffithsCentre for Evolution and Cancer, Division of Molecular Pathology, The Institute of Cancer Research, London, UK.
Kerry FenwickTumour Profiling Unit, The Institute of Cancer Research, London, UK.
Bram HermanDiagnostics and Genomics Group, Agilent Technologies Inc., Santa Clara, CA.
Nik MatthewsTumour Profiling Unit, The Institute of Cancer Research, London, UK.
Ben O'LearyBreast Cancer Now Research Centre, The Institute of Cancer Research, London, UK.
Sanna HulkkiCentre for Molecular Pathology, The Royal Marsden NHS Foundation Trust, Sutton, UK.
David Gonzalez De CastroCentre for Cancer Research and Cell Biology, Belfast, UK.
Anisha PatelDepartment for Radiology, The Royal Marsden NHS Foundation Trust, London and Sutton, UK.
Andrew WotherspoonDepartment of Histopathology, The Royal Marsden NHS Foundation Trust, London and Sutton, UK.
Aleruchi OkachiGastrointestinal Cancer Unit, The Royal Marsden NHS Foundation Trust, London and Sutton, UK.
Isma RanaGastrointestinal Cancer Unit, The Royal Marsden NHS Foundation Trust, London and Sutton, UK.
Ruwaida BegumGastrointestinal Cancer Unit, The Royal Marsden NHS Foundation Trust, London and Sutton, UK.
Matthew N DaviesCentre for Evolution and Cancer, Division of Molecular Pathology, The Institute of Cancer Research, London, UK.
Thomas PowlesBarts Cancer Institute, Queen Mary University of London, London, UK.
Katharina von LogaCentre for Evolution and Cancer, Division of Molecular Pathology, The Institute of Cancer Research, London, UK.
Michael HubankCentre for Molecular Pathology, The Royal Marsden NHS Foundation Trust, Sutton, UK.
Nick TurnerBreast Cancer Now Research Centre, The Institute of Cancer Research, London, UK.
David WatkinsGastrointestinal Cancer Unit, The Royal Marsden NHS Foundation Trust, London and Sutton, UK.
Ian ChauGastrointestinal Cancer Unit, The Royal Marsden NHS Foundation Trust, London and Sutton, UK.
David CunninghamGastrointestinal Cancer Unit, The Royal Marsden NHS Foundation Trust, London and Sutton, UK.
Stefano LiseCentre for Evolution and Cancer, Division of Molecular Pathology, The Institute of Cancer Research, London, UK.
Naureen StarlingGastrointestinal Cancer Unit, The Royal Marsden NHS Foundation Trust, London and Sutton, UK.
Marco GerlingerCentre for Evolution and Cancer, Division of Molecular Pathology, The Institute of Cancer Research, London, UK; marco.gerlinger@icr.ac.uk.
Royal Marsden NHS Foundation Trust · GBInstitute of Cancer Research · GBAgilent Technologies (United States) · USBreast Cancer Now · GBQueen Mary University of London · GBThe Northern Ireland Cancer Centre · GB

Funding

Cancer Research UK 18377Department of HealthMedical Research Council MR/N002121/1Wellcome TrustWellcome Trust 105104/Z/14/Z
6 · The paper itself

Abstract

backgroundCirculating free DNA sequencing (cfDNA-Seq) can portray cancer genome landscapes, but highly sensitive and specific technologies are necessary to accurately detect mutations with often low variant frequencies.

methodsWe developed a customizable hybrid-capture cfDNA-Seq technology using off-the-shelf molecular barcodes and a novel duplex DNA molecule identification tool for enhanced error correction.

resultsModeling based on cfDNA yields from 58 patients showed that this technology, requiring 25 ng of cfDNA, could be applied to >95% of patients with metastatic colorectal cancer (mCRC). cfDNA-Seq of a 32-gene, 163.3-kbp target region detected 100% of single-nucleotide variants, with 0.15% variant frequency in spike-in experiments. Molecular barcode error correction reduced false-positive mutation calls by 97.5%. In 28 consecutively analyzed patients with mCRC, 80 out of 91 mutations previously detected by tumor tissue sequencing were called in the cfDNA. Call rates were similar for point mutations and indels. cfDNA-Seq identified typical mCRC driver mutations in patients in whom biopsy sequencing had failed or did not include key mCRC driver genes. Mutations only called in cfDNA but undetectable in matched biopsies included a subclonal resistance driver mutation to anti-EGFR antibodies in

conclusionsThis error-corrected, ultradeep cfDNA-Seq technology with a customizable target region and publicly available bioinformatics tools enables broad insights into cancer genomes and evolution. CLINICALTRIALSGOV IDENTIFIER: NCT02112357.

Indexed as

MutationBiomarkers, TumorCirculating Tumor DNAColorectal NeoplasmsDNA Copy Number VariationsDNA Mutational AnalysisGenome-Wide Association StudyHigh-Throughput Nucleotide SequencingHumansNeoplasm MetastasisSensitivity and SpecificityBiomarkers, TumorCirculating Tumor DNA

Identifiers

PMID30150316
PMCPMC6214522
OpenAlexW2766307464

What OpenQuestion holds

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Read underepoch 390

Registered trials

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 OpenQuestion graph.