ArticleCancer discovery2023
The Origin of Highly Elevated Cell-Free DNA in Healthy Individuals and Patients with Pancreatic, Colorectal, Lung, or Ovarian Cancer.
Article in Cancer discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers, 2 of them syntheses that pooled it.
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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.
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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
109 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Circulating proteins associated with histological subtypes of lung cancer from genetic and population-based perspectives.PLoS genetics · 2025Pooled it
- Innovative technologies and their clinical prospects for early lung cancer screening.Clinical and experimental medicine · 2025Pooled it
- A multi-analyte blood test for acute spinal cord injury.The Journal of clinical investigation · 2025Trial
- Pancreatic Cancer Early Detection Biomarkers for High-Risk Individuals: Insights From the PRECEDE Consortium.International journal of cancer · 2026Review
- Reappraising the topology of cell-free fetal DNA in maternal blood toward improved prenatal genetic diagnostics.Science advances · 2026Review
- Towards liquid biopsy-based analysis of antitumour immunity.Nature reviews. Clinical oncology · 2026Review
- Immunosuppression-free Nonvascularized Rectus Fascia Allotransplantation for Complex Hernia Repair.Transplantation direct · 2026Article
- Clinical validation of a multi-model blood cfDNA methylation assay for early-stage gastrointestinal cancer screening.Journal of advanced research · 2026Article
- Plasma proteomics improves thrombosis prediction in patients with cancer and identifies targetable IL-17-driven endothelial activation.Science translational medicine · 2026Article
- Circulating DNA reveals nucleosome occupancy patterns that are associated with nucleosome-DNA affinity and are affected in cancer.Genome medicine · 2026Article
- Assessing the exercise-related kinetics of circulating cell-free DNA, circulating tumour DNA, DNase I activity and cytokines in patients with solid tumours: A pilot study.Experimental physiology · 2026Article
- Multimodal analysis of cell-free DNA identifies epigenetic biomarkers for amyotrophic lateral sclerosis diagnosis and progression.The Journal of clinical investigation · 2026Article
- Translational Perspectives on Cell-Free Mitochondrial DNA as a Biomarker in Gynecological Cancers: Current Limitations and Future Research Directions.Biomolecules · 2026Review
- Post-surgery level of circulating DNA in stage III colon cancer patients: Impact on the reliability of minimal residual disease detection.International journal of cancer · 2026Article
- LCPBert: ProtBERT-based early-stage lung cancer prediction from T cell receptor beta sequences.iScience · 2026Article
- Long-read sequencing identifies aberrant fragmentation patterns linked to elevated cell-free DNA levels in cancer.Genome biology · 2026Article
- Longitudinal cell-free DNA methylome and fragmentome profiles in health uncover signatures of cell type and demographic origin.Genome medicine · 2026Article
- fRagmentomics: an R package for integrating cell-free DNA fragment features with mutational status to support liquid biopsy interpretation.Bioinformatics (Oxford, England) · 2026Article
- Prognostic significance and immune correlation of STING expression and promoter methylation in renal cell carcinoma.Scientific reports · 2026Article
- DNMT/TET Imbalance and Network-Level DNA Methylation Remodeling in Ovarian Aging: Mechanistic Perspectives.Biology · 2026Review
49 more citing papers are in PubMed but not listed here.
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23 authors.
Funding
Abstract
Cell-free DNA (cfDNA) concentrations from patients with cancer are often elevated compared with those of healthy controls, but the sources of this extra cfDNA have never been determined. To address this issue, we assessed cfDNA methylation patterns in 178 patients with cancers of the colon, pancreas, lung, or ovary and 64 patients without cancer. Eighty-three of these individuals had cfDNA concentrations much greater than those generally observed in healthy subjects. The major contributor of cfDNA in all samples was leukocytes, accounting for ∼76% of cfDNA, with neutrophils predominating. This was true regardless of whether the samples were derived from patients with cancer or the total plasma cfDNA concentration. High levels of cfDNA observed in patients with cancer did not come from either neoplastic cells or surrounding normal epithelial cells from the tumor's tissue of origin. These data suggest that cancers may have a systemic effect on cell turnover or DNA clearance. SIGNIFICANCE: The origin of excess cfDNA in patients with cancer is unknown. Using cfDNA methylation patterns, we determined that neither the tumor nor the surrounding normal tissue contributes this excess cfDNA-rather it comes from leukocytes. This finding suggests that cancers have a systemic impact on cell turnover or DNA clearance. See related commentary by Thierry and Pisareva, p. 2122. This article is featured in Selected Articles from This Issue, p. 2109.
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