Platelets sequester extracellular DNA, capturing tumor-derived and free fetal DNA
Lauren C. Murphy, Jeanne Inchauspé, Giampiero Valenzano, Pamela J. Holland, Nikolaos Sousos, Hayley L. Belnoue-Davis, Rong Li, Natalie J. Jooss, Camélia Benlabiod, Eleanor Murphy, Zohar Etzioni, Emelie Shepherd, Lucy Denly, Sujata Biswas, Lin Chen, Jennifer O’Sullivan, Michael P. Rimmer, Abdullah O. Khan, Christina Simoglou Karali, Nadia Nasreddin, Ian S. Hitchcock, Milka Koupenova, Skirmantas Kriaučionis, Jim R. Hughes, Eric O’Neill, Manu Vatish, Paul Rees, Simon J. Leedham, Michael Desborough, Adam J. Mead, Benjamin Schuster‐Böckler, Christopher D. Gregory, Bethan Psaila
Abstract
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.