Evidence map›Paper›PMID 30166531›Full record

ArticleCell death & disease2018

Circulating tumor DNA in patients with colorectal adenomas: assessment of detectability and genetic heterogeneity.

Ni Ni Moe Myint, Ajay M Verma, Daniel Fernandez-Garcia, Panchali Sarmah, Patrick S Tarpey, Saif Sattar Al-Aqbi, Hong Cai, Ricky Trigg, Kevin West, Lynne M Howells and 8 more

Open access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 1 pooled it
1.4field-weighted citation impact, top 21% 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.

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

32 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.

  1. Circulating Cell-Free DNA and Colorectal Cancer: A Systematic Review.International journal of molecular sciences · 2018
    Pooled it
  2. Tumor-specificJCEM case reports · 2026
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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

18 authors at 3 institutions in 2 countries.

Ni Ni Moe MyintLeicester Cancer Research Centre, University of Leicester, Leicester, LE2 7LX, UK.
Ajay M VermaUniversity of Leicester, University Hospital of Leicester, Leicester, LE2 7LX, UK.
Daniel Fernandez-GarciaLeicester Cancer Research Centre, University of Leicester, Leicester, LE2 7LX, UK.
Panchali SarmahLeicester Cancer Research Centre, University of Leicester, Leicester, LE2 7LX, UK.
Patrick S TarpeyWellcome Sanger Institute, Hinxton, CB10 1SA, UK.
Saif Sattar Al-AqbiLeicester Cancer Research Centre, University of Leicester, Leicester, LE2 7LX, UK.
Hong CaiLeicester Cancer Research Centre, University of Leicester, Leicester, LE2 7LX, UK.
Ricky TriggLeicester Cancer Research Centre, University of Leicester, Leicester, LE2 7LX, UK.ORCID 0000-0001-9329-9344
Kevin WestKettering General Hospital NHS Foundation Trust, Kettering, NN16 8UZ, UK.
Lynne M HowellsLeicester Cancer Research Centre, University of Leicester, Leicester, LE2 7LX, UK.
Anne ThomasLeicester Cancer Research Centre, University of Leicester, Leicester, LE2 7LX, UK.
Karen BrownLeicester Cancer Research Centre, University of Leicester, Leicester, LE2 7LX, UK.
David S GutteryLeicester Cancer Research Centre, University of Leicester, Leicester, LE2 7LX, UK.ORCID 0000-0003-0418-580X
Baljit SinghUniversity of Leicester, University Hospital of Leicester, Leicester, LE2 7LX, UK.
Howard J PringleLeicester Cancer Research Centre, University of Leicester, Leicester, LE2 7LX, UK.
Ultan McDermottWellcome Sanger Institute, Hinxton, CB10 1SA, UK.
Jacqui A ShawLeicester Cancer Research Centre, University of Leicester, Leicester, LE2 7LX, UK.
Alessandro RufiniLeicester Cancer Research Centre, University of Leicester, Leicester, LE2 7LX, UK. ar230@le.ac.uk.
University of Leicester · GBWellcome Sanger Institute · GBKettering General Hospital · GB

Funding

Cancer Research UK 13101Cancer Research UK 13462Cancer Research UK 20276Cancer Research UK 23464Cancer Research UK C325/A15575Medical Research Council
6 · The paper itself

Abstract

Improving early detection of colorectal cancer (CRC) is a key public health priority as adenomas and stage I cancer can be treated with minimally invasive procedures. Population screening strategies based on detection of occult blood in the feces have contributed to enhance detection rates of localized disease, but new approaches based on genetic analyses able to increase specificity and sensitivity could provide additional advantages compared to current screening methodologies. Recently, circulating cell-free DNA (cfDNA) has received much attention as a cancer biomarker for its ability to monitor the progression of advanced disease, predict tumor recurrence and reflect the complex genetic heterogeneity of cancers. Here, we tested whether analysis of cfDNA is a viable tool to enhance detection of colon adenomas. To address this, we assessed a cohort of patients with adenomas and healthy controls using droplet digital PCR (ddPCR) and mutation-specific assays targeted to trunk mutations. Additionally, we performed multiregional, targeted next-generation sequencing (NGS) of adenomas and unmasked extensive heterogeneity, affecting known drivers such as APC, KRAS and mismatch repair (MMR) genes. However, tumor-related mutations were undetectable in patients' plasma. Finally, we employed a preclinical mouse model of Apc-driven intestinal adenomas and confirmed the inability to identify tumor-related alterations via cfDNA, despite the enhanced disease burden displayed by this experimental cancer model. Therefore, we conclude that benign colon lesions display extensive genetic heterogeneity, that they are not prone to release DNA into the circulation and are unlikely to be reliably detected with liquid biopsies, at least with the current technologies.

Indexed as

AdenomaAdenomatous Polyposis Coli ProteinAgedAged, 80 and overAnimalsBiomarkers, TumorCirculating Tumor DNAColonic NeoplasmsEarly Detection of CancerFemaleHigh-Throughput Nucleotide SequencingHumansLiquid BiopsyMaleMiceMice, KnockoutAdenomatous Polyposis Coli ProteinBiomarkers, TumorBRAF protein, humanCirculating Tumor DNAKRAS protein, humanProto-Oncogene Proteins B-rafProto-Oncogene Proteins p21(ras)

Identifiers

PMID30166531
PMCPMC6117318
OpenAlexW2889089744

What OpenQuestion holds

Textmetadata
LicenceCC BY
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 OpenQuestion graph.