ArticleBMC medical genomics2020
Absolute measurement of the tissue origins of cell-free DNA in the healthy state and following paracetamol overdose.
Article in BMC medical genomics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 15 citations in OpenAlex.
- Biological basis and clinical translation prospects of circulating cell-free DNA in precision management of breast cancer (Review).Oncology letters · 2026Review
- Cell-free DNA release following psychosocial and physical stress in women and men.Translational psychiatry · 2025Article
- Cell-free nucleic acid fragmentomics: A non-invasive window into cellular epigenomes.Translational oncology · 2024Review
- The Role of Mechanistic Biomarkers in Understanding Acetaminophen Hepatotoxicity in Humans.Drug metabolism and disposition: the biological fate of chemicals · 2024Review
- Integrated, Longitudinal Analysis of Cell-free DNA in Uveal Melanoma.Cancer research communications · 2023Article
- PINK1 drives production of mtDNA-containing extracellular vesicles to promote invasiveness.The Journal of cell biology · 2021Article
- Leveraging the Fragment Length of Circulating Tumour DNA to Improve Molecular Profiling of Solid Tumour Malignancies with Next-Generation Sequencing: A Pathway to Advanced Non-invasive Diagnostics in Precision Oncology?Molecular diagnosis & therapy · 2021Review
- Comprehensive cell type decomposition of circulating cell-free DNA with CelFiE.Nature communications · 2021Article
- Circulating cell-free DNA, peripheral lymphocyte subsets alterations and neutrophil lymphocyte ratio in assessment of COVID-19 severity.Innate immunity · 2021Article
- DNA Methylation in Nonalcoholic Fatty Liver Disease.International journal of molecular sciences · 2020Review
- Cell-free DNA for genomic profiling and minimal residual disease monitoring in Myeloma- are we there yet?American journal of blood research · 2020Review
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundDespite the emergence of cell-free DNA (cfDNA) as a clinical biomarker in cancer, the tissue origins of cfDNA in healthy individuals have to date been inferred only by indirect and relative measurement methods, such as tissue-specific methylation and nucleosomal profiling.
methodsWe performed the first direct, absolute measurement of the tissue origins of cfDNA, using tissue-specific knockout mouse strains, in both healthy mice and following paracetamol (APAP) overdose. We then investigated the utility of total cfDNA and the percentage of liver-specific cfDNA as clinical biomarkers in patients presenting with APAP overdose.
resultsAnalysis of cfDNA from healthy tissue-specific knockout mice showed that cfDNA originates predominantly from white and red blood cell lineages, with minor contribution from hepatocytes, and no detectable contribution from skeletal and cardiac muscle. Following APAP overdose in mice, total plasma cfDNA and the percentage fraction originating from hepatocytes increased by ~ 100 and ~ 19-fold respectively. Total cfDNA increased by an average of more than 236-fold in clinical samples from APAP overdose patients with biochemical evidence of liver injury, and 18-fold in patients without biochemically apparent liver injury. Measurement of liver-specific cfDNA, using droplet digital PCR and methylation analysis, revealed that the contribution of liver to cfDNA was increased by an average of 175-fold in APAP overdose patients with biochemically apparent liver injury compared to healthy subjects, but was not increased in overdose patients with normal liver function tests.
conclusionsWe present a novel method for measurement of the tissue origins of cfDNA in healthy and disease states and demonstrate the potential of cfDNA as a clinical biomarker in APAP overdose.
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