Abstract
Physical activity impacts immune homeostasis and leads to rapid and marked increase in cell-free DNA (cfDNA). However, the origin of cfDNA during exercise remains elusive and it is unknown if physical activity could improve or interfere with methylation based liquid biopsy. We analyzed the methylation levels of four validated CpGs representing cfDNA from granulocytes, lymphocytes, monocytes, and non-hematopoietic cells, in healthy individuals in response to exercise, and in patients with hematological malignancies under resting conditions. The analysis revealed that physical activity almost exclusively triggered DNA release from granulocytes, highlighting the relevance as a pre-analytical variable which could compromise diagnostic accuracy.Graphical
Highlights
Circulating cell-free DNA opened up a new horizon for genomic analyses, including absolute quantification, fragmentation profile analysis, detection of mutations and copy number variations, as well as epigenetic profiling [1]
Study collective The study comprised of 10 healthy participants with a mean age of 26.0 ± 5.6 years and 6 patients aged 57.4 ± 11.6 with hematologic malignancies, including low risk myelodysplastic syndrome (LR Low risk myelodysplastic syndrome (MDS)), chronic myelomonocytic leukemia (CMML), myelodysplastic/myeloproliferative neoplasm (MDS/MPN), myelofibrosis, and two patients with polycythemia vera (PV)
Analysis of cell-free DNA (cfDNA) methylation is a promising approach with potential clinical applications in the field of oncology and hemato-oncology [1]
Summary
Circulating cell-free DNA (cfDNA) opened up a new horizon for genomic analyses, including absolute quantification, fragmentation profile analysis, detection of mutations and copy number variations, as well as epigenetic profiling [1]. Exercise-induced cfDNA releases could interfere with, or improve the diagnostic accuracy of methylation specific testing, depending on whether the DNA is derived from the clinically relevant cell type. We used targeted methylation analysis with the pre-validated CpG sites to assess the origin of cfDNA in healthy participants with a longitudinal design—before, after, and 30 min after exercise—to consider the inter-individual variation.
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