Evidence map›Paper›PMID 30172241›Full record

ArticleTranslational oncology2018

Somatic TP53 Mutations Are Detectable in Circulating Tumor DNA from Children with Anaplastic Wilms Tumors.

Taryn D Treger, Tasnim Chagtai, Robert Butcher, George D Cresswell, Reem Al-Saadi, Jesper Brok, Richard D Williams, Chrissy Roberts, Nicholas M Luscombe, Kathy Pritchard Jones and 1 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Translational oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.3field-weighted citation impact, top 20% 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

16 citing papers in PubMed, 31 citations in OpenAlex.

  1. Trial
  2. 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
    Trial
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  15. The genetic changes of Wilms tumour.Nature reviews. Nephrology · 2019
    Review
  16. Wilms Tumor With Raised Serum Alpha-Fetoprotein: Highlighting the Need for Novel Circulating Biomarkers.Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society
    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

11 authors at 3 institutions in 2 countries.

Taryn D TregerUCL Great Ormond Street Institute of Child Health, London, UK; Francis Crick Institute, London, UK. Electronic address: t.treger@ucl.ac.uk.
Tasnim ChagtaiUCL Great Ormond Street Institute of Child Health, London, UK.
Robert ButcherClinical Research Department, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK.
George D CresswellFrancis Crick Institute, London, UK.
Reem Al-SaadiUCL Great Ormond Street Institute of Child Health, London, UK.
Jesper BrokUCL Great Ormond Street Institute of Child Health, London, UK; Department of Paediatric Haematology and Oncology, Rigshospitalet, Copenhagen University Hospital, Denmark.
Richard D WilliamsUCL Great Ormond Street Institute of Child Health, London, UK.
Chrissy RobertsClinical Research Department, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK.
Nicholas M LuscombeFrancis Crick Institute, London, UK; UCL Genetics Institute, Department of Genetics, Evolution & Environment, University College London, UK.
Kathy Pritchard JonesUCL Great Ormond Street Institute of Child Health, London, UK; Department of Paediatric Haematology and Oncology, Great Ormond Street Hospital, London, UK.
William MifsudUCL Great Ormond Street Institute of Child Health, London, UK; Department of Histopathology, Great Ormond Street Hospital, London, UK. Electronic address: wmifsud@sidra.org.
Great Ormond Street Hospital · GBLondon School of Hygiene & Tropical Medicine · GBThe Francis Crick Institute · GB

Funding

Cancer Research UK 17297Wellcome Trust
6 · The paper itself

Abstract

backgroundDiffuse anaplastic Wilms tumor (DAWT) is a rare, high-risk subtype that is often missed on diagnostic needle biopsy. Somatic mutations in TP53 are associated with the development of anaplasia and with poorer survival, particularly in advanced-stage disease. Early identification of DAWT harboring TP53 abnormalities could improve risk stratification of initial therapy and monitoring for recurrence.

methodsDroplet digital polymerase chain reaction (ddPCR) was used to evaluate 21 samples from 4 patients with DAWT. For each patient, we assessed TP53 status in frozen tumor, matched germline DNA, and circulating tumor DNA (ctDNA) from plasma, serum, and urine collected throughout treatment.

resultsMutant TP53 was detectable in ctDNA from plasma and serum in all patients. We did not detect variant TP53 in the same volume (200 μl) of urine. One patient displayed heterogeneity of TP53 in the tumor despite both histological sections displaying anaplasia. Concentration of ctDNA from plasma/serum taken prenephrectomy varied significantly between patients, ranging from 0.44 (0.05-0.90) to 125.25 (109.75-140.25) copies/μl. We observed variation in ctDNA throughout treatment, and in all but one patient, ctDNA levels fell significantly following nephrectomy.

conclusionWe demonstrate for the first time that ddPCR is an effective method for detection of mutant TP53 in ctDNA from children with DAWT even when there is intratumoral somatic heterogeneity. This should be further explored in a larger cohort of patients, as early detection of circulating variant TP53 may have significant clinical impact on future risk stratification and surveillance.

Identifiers

PMID30172241
PMCPMC6121832
OpenAlexW2889081079

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.