Comparison of cell-free and small extracellular-vesicle-associated DNA by sequencing plasma of lung cancer patients
Norbert Moldovan,
Sandra Verkuijlen,
Ymke van der Pol,
Leontien Bosch,
Jan R.T. van Weering,
Idris Bahce,
D. Michiel Pegtel,
Florent Mouliere
Affiliations
Norbert Moldovan
Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Pathology, Cancer Center Amsterdam, 1081 HV Amsterdam, the Netherlands
Sandra Verkuijlen
Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Pathology, Cancer Center Amsterdam, 1081 HV Amsterdam, the Netherlands
Ymke van der Pol
Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Pathology, Cancer Center Amsterdam, 1081 HV Amsterdam, the Netherlands
Leontien Bosch
Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Pathology, Cancer Center Amsterdam, 1081 HV Amsterdam, the Netherlands
Jan R.T. van Weering
Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Human Genetics and Functional Genomics, Center for Neurogenomics and Cognitive Research, 1081 HV Amsterdam, the Netherlands
Idris Bahce
Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Pulmonology, Cancer Center Amsterdam, 1081 HV Amsterdam, the Netherlands
D. Michiel Pegtel
Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Pathology, Cancer Center Amsterdam, 1081 HV Amsterdam, the Netherlands; Corresponding author
Florent Mouliere
Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Pathology, Cancer Center Amsterdam, 1081 HV Amsterdam, the Netherlands; Cancer Research UK National Biomarker Centre, University of Manchester, Manchester, UK; Corresponding author
Summary: Blood contains multiple analytes that can be used as liquid biopsy to analyze cancer. Mutations have been detected in DNA associated with small extracellular vesicles (sEVs). The genome-wide composition and structure of sEV DNA remains poorly characterized, and whether sEVs are enriched in tumor signal compared to cell-free DNA (cfDNA) is unclear. Here, using whole-genome sequencing from lung cancer patients we determined that the tumor fraction and heterogeneity are comparable between DNA associated with sEV (1000 bp fragments poor in tumor signal. The structural patterns of sEV DNA are related to plasma cfDNA. Mitochondrial DNA is relatively enriched in the sEV fractions. Our results suggest that DNA associated to sEV (including exosomes) is not preferentially enriched in tumor signal and is less abundant than cfDNA.
