ArticleJCI insight2022
Cell-free DNA topology depends on its subcellular and cellular origins in cancer.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 19 citations in OpenAlex.
- Reappraising the topology of cell-free fetal DNA in maternal blood toward improved prenatal genetic diagnostics.Science advances · 2026Review
- Liquid Biopsy in Primary CNS Tumors: Bridging Biology, Technology, and Clinical Care.Molecular diagnosis & therapy · 2026Review
- Cell-free DNA in precision medicine: overcoming biological barriers through integrated nanoparticle platforms for simultaneous diagnosis and therapy.Journal of nanobiotechnology · 2026Review
- DNASE1L3 surveils mitochondrial DNA on the surface of distinct mammalian cells.bioRxiv : the preprint server for biology · 2025Article
- Mitogenomic Alterations in Breast Cancer: Identification of Potential Biomarkers of Risk and Prognosis.International journal of molecular sciences · 2025Article
- Modulating cell-free DNA biology as the next frontier in liquid biopsies.Trends in cell biology · 2025Review
- Methylated Reprimo Cell-Free DNA as a Non-Invasive Biomarker for Gastric Cancer.International journal of molecular sciences · 2025Article
- Minimal residual disease as a target for liquid biopsy in patients with solid tumours.Nature reviews. Clinical oncology · 2025Review
- Melanoma's New Frontier: Exploring the Latest Advances in Blood-Based Biomarkers for Melanoma.Cancers · 2024Review
- Analyzing Extracellular Vesicle-associated DNA Using Transmission Electron Microscopy at the Single EV-level.Current protocols · 2024Article
- Extracellular vesicle-associated DNA: ten years since its discovery in human blood.Cell death & disease · 2024Review
- Genomic approaches to cancer and minimal residual disease detection using circulating tumor DNA.Journal for immunotherapy of cancer · 2023Review
- Extracellular vesicles as a potential source of tumor-derived DNA in advanced pancreatic cancer.PloS one · 2023Article
- Comparison of the structures and topologies of plasma extracted circulating nuclear and mitochondrial cell-free DNA.Frontiers in genetics · 2023Article
- Isolation of salivary cell-free DNA for cancer detection.PloS one · 2023Article
- Cell-Free DNA Fragmentomics: A Promising Biomarker for Diagnosis, Prognosis and Prediction of Response in Breast Cancer.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Cancer cells release large quantities of cell-free DNA (cfDNA) into the surrounding tissue and circulation. As cfDNA is a common source of biomarkers for liquid biopsy and has been implicated as a functional mediator for intercellular communication, fundamental characterization of cfDNA topology has widespread biological and clinical ramifications. Whether the topology of cfDNA is such that it exists predominantly in membrane-bound extracellular vesicles (EVs) or in nonvesicular DNA-protein complexes remains poorly understood. Here, we employed a DNA-targeted approach to comprehensively assess total cfDNA topology in cancer. Using preclinical models and patient samples, we demonstrate that nuclear cfDNA is predominantly associated with nucleosomal particles and not EVs, while a substantial subset of mitochondrial cfDNA is membrane protected and disproportionately derived from nontumor cells. In addition, discrimination between membrane-protected and accessible mitochondrial cfDNA added diagnostic and prognostic value in a cohort of head and neck cancer patients. Our results support a revised model for cfDNA topology in cancer. Due to its abundance, nuclear cfDNA within nucleosomal particles is the most compelling liquid biopsy substrate, while EV-bound and accessible mitochondrial cfDNA represent distinct reservoirs of potential cancer biomarkers whose structural conformations may also influence their extracellular stability and propensity for uptake by recipient cells.
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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.