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    Comparison of cell-free and small extracellular-vesicle-associated DNA by sequencing plasma of lung cancer patients

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    Authors
    Moldovan, N.
    Verkuijlen, S.
    van der Pol, Y.
    Bosch, L.
    van Weering, J. R. T.
    Bahce, I.
    Pegtel, D. M.
    Mouliere, Florent
    Affiliation
    Cancer Research UK National Biomarker Centre, University of Manchester, Manchester, UK.
    Issue Date
    2024
    
    Metadata
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    Abstract
    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 (<200 nm) and matched plasma cfDNA. sEV DNA, obtained with size-exclusion chromatography, is composed of short ∼150-180 bp fragments and long >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.
    Citation
    Moldovan N, Verkuijlen S, van der Pol Y, Bosch L, van Weering JRT, Bahce I, et al. Comparison of cell-free and small extracellular-vesicle-associated DNA by sequencing plasma of lung cancer patients. iScience. 2024 Sep 20;27(9):110742. PubMed PMID: 39262778. Pubmed Central PMCID: PMC11389540. Epub 2024/09/12. eng.
    Journal
    iScience
    URI
    http://hdl.handle.net/10541/627229
    DOI
    10.1016/j.isci.2024.110742
    PubMed ID
    39262778
    Additional Links
    https://dx.doi.org/10.1016/j.isci.2024.110742
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.isci.2024.110742
    Scopus Count
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    All Paterson Institute for Cancer Research

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