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, Kim E. Nichols, Jo Anson, Wendy Kohlmann, Haifan Gong, Jodi Lees, Noa Alon, Ledia Brunga, Anita Villani, Kelvin C. Andrade, Payal P. Khincha, Sharon A. Savage, Joshua D. Schiffman, Trevor J. Pugh, David Malkin () and Anna Goldenberg ()
Additional contact information
Vallijah Subasri: The Hospital for Sick Children
Benjamin Brew: The Hospital for Sick Children
Brianne Laverty: The Hospital for Sick Children
Lauren Erdman: The Hospital for Sick Children
Tanya Guha: The Hospital for Sick Children
Jordan R. Hansford: Royal Children’s Hospital
Elizabeth Cairney: Children’s Hospital at London Health Sciences Centre
Carol Portwine: McMaster University
Christine Elser: University of Toronto
Jonathan L. Finlay: The Ohio State University College of Medicine
Kim E. Nichols: St Jude Children’s Research Hospital
Jo Anson: University of Utah
Wendy Kohlmann: University of Utah
Haifan Gong: The Hospital for Sick Children
Jodi Lees: The Hospital for Sick Children
Noa Alon: The Hospital for Sick Children
Ledia Brunga: The Hospital for Sick Children
Anita Villani: The Hospital for Sick Children
Kelvin C. Andrade: National Institutes of Health
Payal P. Khincha: National Institutes of Health
Sharon A. Savage: National Institutes of Health
Joshua D. Schiffman: University of Utah
Trevor J. Pugh: University of Toronto
David Malkin: The Hospital for Sick Children
Anna Goldenberg: The Hospital for Sick Children

Nature Communications, 2025, vol. 16, issue 1, 1-12

Abstract: 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

Date: 2025
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DOI: 10.1038/s41467-025-62894-5

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