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Updated: Jan 10, 2026

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Detection of Cell-Free DNA in Blood Plasma Samples of Cancer Patients
Published on: September 9, 2020
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Histone-based liquid biopsy discriminates between myelodysplastic syndrome and solid malignancies.
Desislava K Tsoneva1,2, Diana Buzova3, Salvatore Daniele Bianco4
1Department of Medical Genetics, Medical University of Varna, Varna, Bulgaria.
Clinical Epigenetics
|November 22, 2025
Summary
Circulating histone signatures can differentiate hematological malignancies like myelodysplastic syndrome (MDS) from solid cancers. This novel approach using advanced flow cytometry may improve cancer diagnosis and lead to point-of-care devices.
Area of Science:
- Oncology
- Biochemistry
- Molecular Biology
Background:
- Hematological and solid cancers exhibit distinct clinical behaviors despite shared hallmarks.
- Circulating histone populations are detectable in biological fluids and may serve as biomarkers.
- Lack of studies comparing circulating histone complexity across healthy individuals, hematological malignancies, and solid cancers.
Purpose of the Study:
- To identify circulating histone signatures differentiating hematological from solid malignancies.
- To explore the potential of histone profiles in aiding differential cancer diagnosis.
- To investigate the feasibility of developing point-of-care diagnostic devices based on histone biomarkers.
Main Methods:
- Assessed plasma histone signatures in healthy subjects (n=30) and patients with myelodysplastic syndrome (MDS, n=43), colorectal cancer (CRC, n=39), lung cancer (NSCLC, n=15; SCLC, n=4), and breast cancer (BC, n=16).
- Utilized Principal Component Analysis (PCA) to analyze circulating histone and histone complex profiles.
- Employed ImageStream(X)-advanced flow cytometry to quantify individual histones (H2A, H2B, H3, H4, macroH2A1.1, macroH2A1.2), histone dimers, and nucleosomes.
Main Results:
- Circulating histone abundance was generally increased in cancer patients compared to healthy controls.
- Distinct histone signatures segregated MDS from solid cancers, with increased H2A and macroH2A1.2 and decreased H2A/H2B/H3/H4 and H3/H4 complexes observed in MDS.
- macroH2A1.2 and H2A/H2B/H3/H4 levels showed differential age correlations in healthy subjects versus MDS patients.
Conclusions:
- Identified circulating histone signatures capable of discriminating between solid cancers and MDS.
- Demonstrated the utility of a rapid, non-invasive imaging technology for cancer diagnosis.
- Highlighted the potential of circulating histones as biomarkers for improved differential diagnosis of malignancies.

