Evidence map›Paper›PMID 40858599›Full record

ArticleNature communications2025

Peripheral blood DNA methylation predicts the early onset of primary tumor in TP53 mutation carriers.

Vallijah Subasri, Benjamin Brew, Brianne Laverty, Lauren Erdman, Tanya Guha, Jordan R Hansford, Elizabeth Cairney, Carol Portwine, Christine Elser, Jonathan L Finlay and 15 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

25 authors.

Vallijah Subasri *Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.ORCID http://orcid.org/0000-0002-6584-877X
Benjamin Brew *Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
Brianne LavertyGenetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.ORCID http://orcid.org/0000-0002-7245-0831
Lauren ErdmanGenetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
Tanya GuhaGenetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
Jordan R HansfordChildren's Cancer Centre, Royal Children's Hospital, Melbourne, VIC, Australia.ORCID http://orcid.org/0000-0001-7733-383X
Elizabeth CairneyDepartment of Pediatrics, Children's Hospital at London Health Sciences Centre, London, ON, Canada.
Carol PortwineDepartment of Pediatrics, McMaster University, Hamilton, ON, Canada.
Christine ElserFaculty of Medicine, University of Toronto, Toronto, ON, Canada.
Jonathan L FinlayPediatrics and Radiation Oncology, The Ohio State University College of Medicine, Columbus, OH, USA.
Kim E NicholsDepartment of Oncology, St Jude Children's Research Hospital, Memphis, TN, USA.ORCID http://orcid.org/0000-0002-5581-6555
Jo AnsonHuntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
Wendy KohlmannHuntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
Haifan GongGenetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
Jodi LeesGenetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
Noa AlonGenetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
Ledia BrungaGenetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
Anita VillaniDivision of Hematology/Oncology, The Hospital for Sick Children, Toronto, ON, Canada.
Kelvin C de AndradeClinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Payal P KhinchaClinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Sharon A SavageClinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0001-6006-0740
Joshua D SchiffmanDepartment of Pediatrics, University of Utah, Salt Lake City, UT, USA.ORCID http://orcid.org/0000-0002-6968-7694
Trevor J PughDepartment of Medical Biophysics, University of Toronto, Toronto, ON, Canada.ORCID http://orcid.org/0000-0002-8073-5888
David MalkinGenetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON, Canada. david.malkin@sickkids.ca.ORCID http://orcid.org/0000-0001-5752-9763
Anna GoldenbergGenetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON, Canada. anna.goldenberg@sickkids.ca.

Funding

Gouvernement du Canada | Instituts de Recherche en Santé du Canada | CIHR Skin Research Training Centre (Skin Research Training Centre) #FDN-143234Terry Fox Research Institute (Institut de Recherche Terry Fox) #1081
6 · The paper itself

Abstract

Li-Fraumeni syndrome (LFS) confers high lifetime cancer risk due to germline TP53 pathogenic variants (PV). A comprehensive surveillance regimen termed the 'Toronto Protocol', has been adopted for early tumor detection, demonstrating improved survival among TP53 PV carriers. However, the protocol's "one-size-fits-all" approach fails to consider individual cancer risk. To personalize screening, we developed a support vector machine model to predict early onset of primary tumors (age < 6) using peripheral blood methylation data of TP53 PV carriers (n = 237). Validation (n = 64) and external testing (n = 79) showed AUROC = 0.928 [0.835-1.000], F1-score = 0.692 [0.435-0.867], and NPV = 0.984 [0.946-1.000]. The model achieved 91% accuracy, correctly classifying 90% of patients with cancer before the age of six and 87% of cancer-free individuals in the external test set. Our tool enables risk stratification for early-onset malignancies, to optimize clinical surveillance and improve patient outcomes.

Indexed as

DNA MethylationLi-Fraumeni SyndromeNeoplasmsTumor Suppressor Protein p53AdolescentAdultAge of OnsetChildChild, PreschoolEarly Detection of CancerFemaleGerm-Line MutationHeterozygoteHumansMaleMiddle AgedTP53 protein, humanTumor Suppressor Protein p53

Identifiers

PMID40858599
PMCPMC12381258

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.