TY - JOUR
T1 - Comparison of cell-free and small extracellular-vesicle-associated DNA by sequencing plasma of lung cancer patients
AU - Moldovan, Norbert
AU - Verkuijlen, Sandra
AU - van der Pol, Ymke
AU - Bosch, Leontien
AU - van Weering, Jan R.T.
AU - Bahce, Idris
AU - Pegtel, D. Michiel
AU - Mouliere, Florent
N1 - Publisher Copyright:
© 2024 The Author(s)
PY - 2024/9/20
Y1 - 2024/9/20
N2 - 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.
AB - 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.
KW - Cancer
KW - Cancer systems biology
KW - Molecular genetics
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U2 - 10.1016/j.isci.2024.110742
DO - 10.1016/j.isci.2024.110742
M3 - Article
AN - SCOPUS:85206371324
SN - 2589-0042
VL - 27
SP - 1
EP - 11
JO - iScience
JF - iScience
IS - 9
M1 - 110742
ER -