ArticleScientific reports2021
Serial profiling of cell-free DNA and nucleosome histone modifications in cell cultures.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 46 citations in OpenAlex.
- NINJ1: implications for plasma membrane rupture and disease.Biochemical Society transactions · 2026Review
- The emerging clinical relevance of cell-free DNA in lupus: from mechanistic insights to therapeutic opportunities.Frontiers in immunology · 2026Review
- The Clinical Utility of Cell-Free DNA in Brain Tumor Management: A Comprehensive Review.Journal of molecular neuroscience : MN · 2025Review
- Simulating cell-free chromatin using preclinical cancer models for liquid biopsy applications.iScience · 2025Article
- Myeloperoxidase, extracellular DNA and neutrophil extracellular trap formation in the animal models of metabolic dysfunction-associated steatotic liver disease.World journal of gastroenterology · 2025Article
- Pre-Amplification of Cell-Free DNA: Balancing Amplification Errors with Enhanced Sensitivity.Biomolecules · 2025Article
- Cell-Free DNA: Features and Attributes Shaping the Next Frontier in Liquid Biopsy.Molecular diagnosis & therapy · 2025Review
- Molecular characterization of cell decay in inflammation and topological assignment of released cfDNA for integrative laboratory and radiological outcome assessment.Frontiers in cellular and infection microbiology · 2025Article
- Review
- The Correlation between Plasma Circulating Tumor DNA and Radiographic Tumor Burden.The Journal of molecular diagnostics : JMD · 2024Review
- Circulating Nucleosomes as a Novel Biomarker for Sepsis: A Scoping Review.Biomedicines · 2024Article
- An in vitro CRISPR screen of cell-free DNA identifies apoptosis as the primary mediator of cell-free DNA release.Communications biology · 2024Article
- Designing Epigenome Editors: Considerations of Biochemical and Locus Specificities.Methods in molecular biology (Clifton, N.J.) · 2024Article
- The Challenge to Stabilize, Extract and Analyze Urinary Cell-Free DNA (ucfDNA) during Clinical Routine.Diagnostics (Basel, Switzerland) · 2023Article
- The changing face of circulating tumor DNA (ctDNA) profiling: Factors that shape the landscape of methodologies, technologies, and commercialization.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2023Article
- Multidimensional fragmentomic profiling of cell-free DNA released from patient-derived organoids.Human genomics · 2023Article
- The Origin of Highly Elevated Cell-Free DNA in Healthy Individuals and Patients with Pancreatic, Colorectal, Lung, or Ovarian Cancer.Cancer discovery · 2023Article
- The role of circulating cell-free DNA as an inflammatory mediator after stroke.Seminars in immunopathology · 2023Review
- Application of PCR-based approaches for evaluation of cell-free DNA fragmentation in colorectal cancer.Frontiers in molecular biosciences · 2023Article
- Profiling of cell-free DNA methylation and histone signatures in pediatric NAFLD: A pilot study.Hepatology communications · 2022Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent advances in basic research have unveiled several strategies for improving the sensitivity and specificity of cell-free DNA (cfDNA) based assays, which is a prerequisite for broadening its clinical use. Included among these strategies is leveraging knowledge of both the biogenesis and physico-chemical properties of cfDNA towards the identification of better disease-defining features and optimization of methods. While good progress has been made on this front, much of cfDNA biology remains uncharted. Here, we correlated serial measurements of cfDNA size, concentration and nucleosome histone modifications with various cellular parameters, including cell growth rate, viability, apoptosis, necrosis, and cell cycle phase in three different cell lines. Collectively, the picture emerged that temporal changes in cfDNA levels are rather irregular and not the result of constitutive release from live cells. Instead, changes in cfDNA levels correlated with intermittent cell death events, wherein apoptosis contributed more to cfDNA release in non-cancer cells and necrosis more in cancer cells. Interestingly, the presence of a ~ 3 kbp cfDNA population, which is often deemed to originate from accidental cell lysis or active release, was found to originate from necrosis. High-resolution analysis of this cfDNA population revealed an underlying DNA laddering pattern consisting of several oligo-nucleosomes, identical to those generated by apoptosis. This suggests that necrosis may contribute significantly to the pool of mono-nucleosomal cfDNA fragments that are generally interrogated for cancer mutational profiling. Furthermore, since active steps are often taken to exclude longer oligo-nucleosomes from clinical biospecimens and subsequent assays this raises the question of whether important pathological information is lost.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.