Platelets sequester extracellular DNA, capturing tumor-derived and free fetal DNA
Platelets are anucleate blood cells vital for hemostasis and immunity. During cell death and aberrant mitosis, nucleated cells release DNA, resulting in "cell-free" DNA in plasma (cfDNA). An excess of cfDNA is deleterious. Given their ability to internalize pathogen-derived nucleic acids, we hypothesized that platelets may also clear endogenous cfDNA. We found that, despite lacking a nucleus, platelets contained a repertoire of DNA fragments mapping across the nuclear genome. We detected fetal DNA in maternal platelets and cancer-derived DNA in platelets from patients with premalignant and cancerous lesions. As current liquid biopsy approaches utilize platelet-depleted plasma, important genetic information contained within platelets is being missed. This study establishes a physiological role for platelets that has not previously been highlighted, with broad translational relevance.
Authors
- Camélia Benlabiod (ORCID: https://orcid.org/0000-0001-7119-9326)
- Jennifer O’Sullivan (ORCID: https://orcid.org/0000-0003-0502-7133)
- Nikolaos Sousos (ORCID: https://orcid.org/0000-0002-9100-2954)
- Sujata Biswas (ORCID: https://orcid.org/0000-0002-0700-7286)
- Jeanne Inchauspé (ORCID: https://orcid.org/0000-0003-4489-423X)
- Adam J. Mead (ORCID: https://orcid.org/0000-0001-8522-1002)
- Milka Koupenova (ORCID: https://orcid.org/0000-0001-5934-8990)
- Benjamin Schuster‐Böckler (ORCID: https://orcid.org/0000-0002-8892-5133)
- Natalie J. Jooss (ORCID: https://orcid.org/0000-0002-2314-4993)
- Abdullah O. Khan (ORCID: https://orcid.org/0000-0003-0825-3179)
- Michael Desborough (ORCID: https://orcid.org/0000-0002-1951-5616)
- Eric O’Neill (ORCID: https://orcid.org/0000-0002-0060-6278)
- Michael P. Rimmer (ORCID: https://orcid.org/0000-0002-3295-8753)
- Jim R. Hughes (ORCID: https://orcid.org/0000-0002-8955-7256)
- Bethan Psaila (ORCID: https://orcid.org/0000-0001-8198-9663)
- Lucy Denly (ORCID: https://orcid.org/0000-0001-9915-4760)
- Manu Vatish (ORCID: https://orcid.org/0000-0002-6012-2574)
- Skirmantas Kriaučionis (ORCID: https://orcid.org/0000-0002-2273-5994)
- Nadia Nasreddin (ORCID: https://orcid.org/0000-0002-3025-6213)
- Ian S. Hitchcock (ORCID: https://orcid.org/0000-0001-7170-6703)
- Hayley L. Belnoue-Davis (ORCID: https://orcid.org/0000-0003-2914-4932)
- Eleanor Murphy (ORCID: https://orcid.org/0000-0002-3600-1158)
- Lauren C. Murphy (ORCID: https://orcid.org/0000-0001-9506-2762)
- Christopher D. Gregory (ORCID: https://orcid.org/0000-0002-7553-0132)
- Christina Simoglou Karali (ORCID: https://orcid.org/0000-0003-2169-6580)
- Simon J. Leedham (ORCID: https://orcid.org/0000-0003-1476-6982)
- Paul Rees (ORCID: https://orcid.org/0000-0002-7715-6914)
- Giampiero Valenzano (ORCID: https://orcid.org/0009-0000-4882-4066)
- Rong Li (ORCID: https://orcid.org/0000-0002-1805-810X)
- Lin Chen (ORCID: https://orcid.org/0000-0002-2958-6012)
- Pamela J. Holland
- Emelie Shepherd
- Zohar Etzioni
Institutions
- Broad Institute (US)
- Centre for Human Genetics (GB)
- University of Massachusetts Chan Medical School (US)
- John Radcliffe Hospital (GB)
- Swansea University (GB)
- University of Oxford (GB)
- CRUK/MRC Oxford Institute for Radiation Oncology (GB)
- Ludwig Cancer Research (GB)
- MRC Centre for Regenerative Medicine (GB)
- MRC Weatherall Institute of Molecular Medicine (GB)
- MRC Human Immunology Unit (GB)
- Oxford BioMedica (United Kingdom) (GB)
- Oxford University Hospitals NHS Trust (GB)
- Centre for Inflammation Research (GB)
- University of York (GB)
Publication Details
- Journal
- Science
- Published
- 2025-08-14
- DOI
- https://doi.org/10.1126/science.adp3971
- Citations
- 22
- Primary Topic
- Cancer Genomics and Diagnostics
- Type
- article
- Field-Weighted Citation Impact
- 20.60