Circulating H3K27 Methylated Nucleosome Plasma Concentration: Synergistic Information with Circulating Tumor DNA Molecular Profiling.

Autor: Grolleau E; Center for Innovation in Cancerology of Lyon (CICLY) EA 3738, Faculty of Medicine and Maieutic Lyon Sud, Claude Bernard University Lyon I, 69921 Oullins, France.; Pulmonology Department, Lyon Sud Hospital, Hospices Civils de Lyon, 69495 Pierre-Bénite, France., Candiracci J; Belgian Volition SRL, Parc Scientifique Créalys, 5032 Isnes, Belgium., Lescuyer G; Center for Innovation in Cancerology of Lyon (CICLY) EA 3738, Faculty of Medicine and Maieutic Lyon Sud, Claude Bernard University Lyon I, 69921 Oullins, France.; Institute of Pharmaceutical and Biological Sciences (ISPB), Claude Bernard University Lyon I, 69373 Lyon, France.; Department of Biochemistry and Molecular Biology, Lyon-Sud Hospital, Hospices Civils de Lyon, 69495 Pierre-Bénite, France.; Circulating Cancer (CIRCAN) Program, Hospices Civils de Lyon, Cancer Institute, 69495 Pierre-Bénite, France., Barthelemy D; Center for Innovation in Cancerology of Lyon (CICLY) EA 3738, Faculty of Medicine and Maieutic Lyon Sud, Claude Bernard University Lyon I, 69921 Oullins, France.; Institute of Pharmaceutical and Biological Sciences (ISPB), Claude Bernard University Lyon I, 69373 Lyon, France.; Department of Biochemistry and Molecular Biology, Lyon-Sud Hospital, Hospices Civils de Lyon, 69495 Pierre-Bénite, France.; Circulating Cancer (CIRCAN) Program, Hospices Civils de Lyon, Cancer Institute, 69495 Pierre-Bénite, France., Benzerdjeb N; Center for Innovation in Cancerology of Lyon (CICLY) EA 3738, Faculty of Medicine and Maieutic Lyon Sud, Claude Bernard University Lyon I, 69921 Oullins, France.; Pathology Department, Claude Bernard University Lyon I, Hospices Civils de Lyon, 69677 Bron, France., Haon C; Center for Innovation in Cancerology of Lyon (CICLY) EA 3738, Faculty of Medicine and Maieutic Lyon Sud, Claude Bernard University Lyon I, 69921 Oullins, France.; Department of Biochemistry and Molecular Biology, Lyon-Sud Hospital, Hospices Civils de Lyon, 69495 Pierre-Bénite, France.; Circulating Cancer (CIRCAN) Program, Hospices Civils de Lyon, Cancer Institute, 69495 Pierre-Bénite, France., Geiguer F; Center for Innovation in Cancerology of Lyon (CICLY) EA 3738, Faculty of Medicine and Maieutic Lyon Sud, Claude Bernard University Lyon I, 69921 Oullins, France.; Institute of Pharmaceutical and Biological Sciences (ISPB), Claude Bernard University Lyon I, 69373 Lyon, France.; Department of Biochemistry and Molecular Biology, Lyon-Sud Hospital, Hospices Civils de Lyon, 69495 Pierre-Bénite, France.; Circulating Cancer (CIRCAN) Program, Hospices Civils de Lyon, Cancer Institute, 69495 Pierre-Bénite, France., Raffin M; Center for Innovation in Cancerology of Lyon (CICLY) EA 3738, Faculty of Medicine and Maieutic Lyon Sud, Claude Bernard University Lyon I, 69921 Oullins, France.; Institute of Pharmaceutical and Biological Sciences (ISPB), Claude Bernard University Lyon I, 69373 Lyon, France.; Department of Biochemistry and Molecular Biology, Lyon-Sud Hospital, Hospices Civils de Lyon, 69495 Pierre-Bénite, France.; Circulating Cancer (CIRCAN) Program, Hospices Civils de Lyon, Cancer Institute, 69495 Pierre-Bénite, France., Hardat N; Belgian Volition SRL, Parc Scientifique Créalys, 5032 Isnes, Belgium., Balandier J; Center for Innovation in Cancerology of Lyon (CICLY) EA 3738, Faculty of Medicine and Maieutic Lyon Sud, Claude Bernard University Lyon I, 69921 Oullins, France.; Institute of Pharmaceutical and Biological Sciences (ISPB), Claude Bernard University Lyon I, 69373 Lyon, France.; Department of Biochemistry and Molecular Biology, Lyon-Sud Hospital, Hospices Civils de Lyon, 69495 Pierre-Bénite, France.; Circulating Cancer (CIRCAN) Program, Hospices Civils de Lyon, Cancer Institute, 69495 Pierre-Bénite, France., Rabeuf R; Belgian Volition SRL, Parc Scientifique Créalys, 5032 Isnes, Belgium., Chalabreysse L; Pathology Department, Claude Bernard University Lyon I, Hospices Civils de Lyon, 69677 Bron, France., Wozny AS; Department of Biochemistry and Molecular Biology, Lyon-Sud Hospital, Hospices Civils de Lyon, 69495 Pierre-Bénite, France.; Circulating Cancer (CIRCAN) Program, Hospices Civils de Lyon, Cancer Institute, 69495 Pierre-Bénite, France.; Cellular and Molecular Radiobiology Laboratory UMR CNRS5822/IP2I, Faculty of Medicine and Maieutic Lyon Sud, Claude Bernard University Lyon I, 69921 Oullins, France., Rommelaere G; Belgian Volition SRL, Parc Scientifique Créalys, 5032 Isnes, Belgium., Rodriguez-Lafrasse C; Department of Biochemistry and Molecular Biology, Lyon-Sud Hospital, Hospices Civils de Lyon, 69495 Pierre-Bénite, France.; Circulating Cancer (CIRCAN) Program, Hospices Civils de Lyon, Cancer Institute, 69495 Pierre-Bénite, France.; Cellular and Molecular Radiobiology Laboratory UMR CNRS5822/IP2I, Faculty of Medicine and Maieutic Lyon Sud, Claude Bernard University Lyon I, 69921 Oullins, France., Subtil F; Statistic Department, Hospices Civils de Lyon, 69008 Lyon, France.; LBBE, Claude Bernard University Lyon I, UMR 5558, CNRS, 69100 Villeurbanne, France., Couraud S; Center for Innovation in Cancerology of Lyon (CICLY) EA 3738, Faculty of Medicine and Maieutic Lyon Sud, Claude Bernard University Lyon I, 69921 Oullins, France.; Pulmonology Department, Lyon Sud Hospital, Hospices Civils de Lyon, 69495 Pierre-Bénite, France., Herzog M; Belgian Volition SRL, Parc Scientifique Créalys, 5032 Isnes, Belgium., Payen-Gay L; Center for Innovation in Cancerology of Lyon (CICLY) EA 3738, Faculty of Medicine and Maieutic Lyon Sud, Claude Bernard University Lyon I, 69921 Oullins, France.; Institute of Pharmaceutical and Biological Sciences (ISPB), Claude Bernard University Lyon I, 69373 Lyon, France.; Department of Biochemistry and Molecular Biology, Lyon-Sud Hospital, Hospices Civils de Lyon, 69495 Pierre-Bénite, France.; Circulating Cancer (CIRCAN) Program, Hospices Civils de Lyon, Cancer Institute, 69495 Pierre-Bénite, France.
Jazyk: angličtina
Zdroj: Biomolecules [Biomolecules] 2023 Aug 16; Vol. 13 (8). Date of Electronic Publication: 2023 Aug 16.
DOI: 10.3390/biom13081255
Abstrakt: The molecular profiling of circulating tumor DNA (ctDNA) is a helpful tool not only in cancer treatment, but also in the early detection of relapse. However, the clinical interpretation of a ctDNA negative result remains challenging. The characterization of circulating nucleosomes (carrying cell-free DNA) and associated epigenetic modifications (playing a key role in the tumorigenesis of different cancers) may provide useful information for patient management, by supporting the contributive value of ctDNA molecular profiling. Significantly elevated concentrations of H3K27Me3 nucleosomes were found in plasmas at the diagnosis, and during the follow-up, of NSCLC patients, compared to healthy donors ( p -value < 0.0001). By combining the H3K27Me3 level and the ctDNA molecular profile, we found that 25.5% of the patients had H3K27Me3 levels above the cut off, and no somatic alteration was detected at diagnosis. This strongly supports the presence of non-mutated ctDNA in the corresponding plasma. During the patient follow-up, a high H3K27Me3-nucleosome level was found in 15.1% of the sample, despite no somatic mutations being detected, allowing the identification of disease progression from 43.1% to 58.2% over molecular profiling alone. Measuring H3K27Me3-nucleosome levels in combination with ctDNA molecular profiling may improve confidence in the negative molecular result for cfDNA in lung cancer at diagnosis, and may also be a promising biomarker for molecular residual disease (MRD) monitoring, during and/or after treatment.
Databáze: MEDLINE
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