Evidence map›Paper›PMID 25134821›Full record

ArticleGenome biology2014

Methylome analysis identifies a Wilms tumor epigenetic biomarker detectable in blood.

Jocelyn Charlton, Richard D Williams, Mark Weeks, Neil J Sebire, Sergey Popov, Gordan Vujanic, William Mifsud, Marisa Alcaide-German, Lee M Butcher, Stephan Beck and 1 more

Abstract read
In one paragraph

Article in Genome biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing 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

26 citing papers in PubMed.

  1. Circulating Tumor DNA as a Biomarker in Patients With Stage III and IV Wilms Tumor: Analysis From a Children's Oncology Group Trial, AREN0533.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2022
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  9. Circulating Tumor DNA in Pediatric Cancer.Frontiers in molecular biosciences · 2022
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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

11 authors.

Jocelyn Charlton
Richard D Williams
Mark Weeks
Neil J Sebire
Sergey Popov
Gordan Vujanic
William Mifsud
Marisa Alcaide-German
Lee M Butcher
Stephan Beck
Kathy Pritchard-Jones

Funding

Cancer Research UK 17297
6 · The paper itself

Abstract

backgroundWilms tumor is the most common pediatric renal malignancy and there is a clinical need for a molecular biomarker to assess treatment response and predict relapse. The known mutated genes in this tumor type show low mutation frequencies, whereas aberrant methylation at 11p15 is by far the most common aberration. We therefore analyzed the epigenome, rather than the genome, to identify ubiquitous tumor-specific biomarkers.

resultsMethylome analysis of matched normal kidney and Wilms tumor identifies 309 preliminary methylation variable positions which we translate into three differentially methylated regions (DMR) for use as tumor-specific biomarkers. Using two novel algorithms we show that these three DMRs are not confounded by cell type composition. We further show that these DMRs are not methylated in embryonic blastema but are intermediately methylated in Wilms tumor precursor lesions. We validate the biomarker DMRs using two independent sample sets of normal kidney and Wilms tumor and seven Wilms tumor histological subtypes, achieving 100% and 98% correct classification, respectively. As proof-of-principle for clinical utility, we successfully use biomarker DMR-2 in a pilot analysis of cell-free circulating DNA to monitor tumor response during treatment in ten patients.

conclusionsThese findings define the most common methylated regions in Wilms tumor known to date which are not associated with their embryonic origin or precursor stage. We show that this tumor-specific methylated DNA is released into the blood circulation where it can be detected non-invasively showing potential for clinical utility.

Indexed as

DNA MethylationAlgorithmsBiomarkers, TumorCell-Free SystemEpigenesis, GeneticGenome, HumanHumansKidney NeoplasmsPilot ProjectsWilms TumorBiomarkers, Tumor

Identifiers

PMID25134821
PMCPMC4310621

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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.