Circulating H3K27 Methylated Nucleosome Plasma Concentration: Synergistic Information with Circulating Tumor DNA Molecular Profiling
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-fre...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-08-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/13/8/1255 |
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| author | Emmanuel Grolleau Julie Candiracci Gaelle Lescuyer David Barthelemy Nazim Benzerdjeb Christine Haon Florence Geiguer Margaux Raffin Nathalie Hardat Julie Balandier Rémi Rabeuf Lara Chalabreysse Anne-Sophie Wozny Guillaume Rommelaere Claire Rodriguez-Lafrasse Fabien Subtil Sébastien Couraud Marielle Herzog Lea Payen-Gay |
| author_facet | Emmanuel Grolleau Julie Candiracci Gaelle Lescuyer David Barthelemy Nazim Benzerdjeb Christine Haon Florence Geiguer Margaux Raffin Nathalie Hardat Julie Balandier Rémi Rabeuf Lara Chalabreysse Anne-Sophie Wozny Guillaume Rommelaere Claire Rodriguez-Lafrasse Fabien Subtil Sébastien Couraud Marielle Herzog Lea Payen-Gay |
| author_sort | Emmanuel Grolleau |
| collection | DOAJ |
| description | 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 (<i>p</i>-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. |
| first_indexed | 2024-03-11T00:05:53Z |
| format | Article |
| id | doaj.art-e39cda56d70240f48db2b0d280f75cff |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-11T00:05:53Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-e39cda56d70240f48db2b0d280f75cff2023-11-19T00:24:25ZengMDPI AGBiomolecules2218-273X2023-08-01138125510.3390/biom13081255Circulating H3K27 Methylated Nucleosome Plasma Concentration: Synergistic Information with Circulating Tumor DNA Molecular ProfilingEmmanuel Grolleau0Julie Candiracci1Gaelle Lescuyer2David Barthelemy3Nazim Benzerdjeb4Christine Haon5Florence Geiguer6Margaux Raffin7Nathalie Hardat8Julie Balandier9Rémi Rabeuf10Lara Chalabreysse11Anne-Sophie Wozny12Guillaume Rommelaere13Claire Rodriguez-Lafrasse14Fabien Subtil15Sébastien Couraud16Marielle Herzog17Lea Payen-Gay18Center for Innovation in Cancerology of Lyon (CICLY) EA 3738, Faculty of Medicine and Maieutic Lyon Sud, Claude Bernard University Lyon I, 69921 Oullins, FranceBelgian Volition SRL, Parc Scientifique Créalys, 5032 Isnes, BelgiumCenter for Innovation in Cancerology of Lyon (CICLY) EA 3738, Faculty of Medicine and Maieutic Lyon Sud, Claude Bernard University Lyon I, 69921 Oullins, FranceCenter for Innovation in Cancerology of Lyon (CICLY) EA 3738, Faculty of Medicine and Maieutic Lyon Sud, Claude Bernard University Lyon I, 69921 Oullins, FranceCenter for Innovation in Cancerology of Lyon (CICLY) EA 3738, Faculty of Medicine and Maieutic Lyon Sud, Claude Bernard University Lyon I, 69921 Oullins, FranceCenter for Innovation in Cancerology of Lyon (CICLY) EA 3738, Faculty of Medicine and Maieutic Lyon Sud, Claude Bernard University Lyon I, 69921 Oullins, FranceCenter for Innovation in Cancerology of Lyon (CICLY) EA 3738, Faculty of Medicine and Maieutic Lyon Sud, Claude Bernard University Lyon I, 69921 Oullins, FranceCenter for Innovation in Cancerology of Lyon (CICLY) EA 3738, Faculty of Medicine and Maieutic Lyon Sud, Claude Bernard University Lyon I, 69921 Oullins, FranceBelgian Volition SRL, Parc Scientifique Créalys, 5032 Isnes, BelgiumCenter for Innovation in Cancerology of Lyon (CICLY) EA 3738, Faculty of Medicine and Maieutic Lyon Sud, Claude Bernard University Lyon I, 69921 Oullins, FranceBelgian Volition SRL, Parc Scientifique Créalys, 5032 Isnes, BelgiumPathology Department, Claude Bernard University Lyon I, Hospices Civils de Lyon, 69677 Bron, FranceDepartment of Biochemistry and Molecular Biology, Lyon-Sud Hospital, Hospices Civils de Lyon, 69495 Pierre-Bénite, FranceBelgian Volition SRL, Parc Scientifique Créalys, 5032 Isnes, BelgiumDepartment of Biochemistry and Molecular Biology, Lyon-Sud Hospital, Hospices Civils de Lyon, 69495 Pierre-Bénite, FranceStatistic Department, Hospices Civils de Lyon, 69008 Lyon, FranceCenter for Innovation in Cancerology of Lyon (CICLY) EA 3738, Faculty of Medicine and Maieutic Lyon Sud, Claude Bernard University Lyon I, 69921 Oullins, FranceBelgian Volition SRL, Parc Scientifique Créalys, 5032 Isnes, BelgiumCenter for Innovation in Cancerology of Lyon (CICLY) EA 3738, Faculty of Medicine and Maieutic Lyon Sud, Claude Bernard University Lyon I, 69921 Oullins, FranceThe 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 (<i>p</i>-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.https://www.mdpi.com/2218-273X/13/8/1255NSCLCepigeneticshistone PTMH3K27Me3 nucleosomectDNAliquid biopsy |
| spellingShingle | Emmanuel Grolleau Julie Candiracci Gaelle Lescuyer David Barthelemy Nazim Benzerdjeb Christine Haon Florence Geiguer Margaux Raffin Nathalie Hardat Julie Balandier Rémi Rabeuf Lara Chalabreysse Anne-Sophie Wozny Guillaume Rommelaere Claire Rodriguez-Lafrasse Fabien Subtil Sébastien Couraud Marielle Herzog Lea Payen-Gay Circulating H3K27 Methylated Nucleosome Plasma Concentration: Synergistic Information with Circulating Tumor DNA Molecular Profiling Biomolecules NSCLC epigenetics histone PTM H3K27Me3 nucleosome ctDNA liquid biopsy |
| title | Circulating H3K27 Methylated Nucleosome Plasma Concentration: Synergistic Information with Circulating Tumor DNA Molecular Profiling |
| title_full | Circulating H3K27 Methylated Nucleosome Plasma Concentration: Synergistic Information with Circulating Tumor DNA Molecular Profiling |
| title_fullStr | Circulating H3K27 Methylated Nucleosome Plasma Concentration: Synergistic Information with Circulating Tumor DNA Molecular Profiling |
| title_full_unstemmed | Circulating H3K27 Methylated Nucleosome Plasma Concentration: Synergistic Information with Circulating Tumor DNA Molecular Profiling |
| title_short | Circulating H3K27 Methylated Nucleosome Plasma Concentration: Synergistic Information with Circulating Tumor DNA Molecular Profiling |
| title_sort | circulating h3k27 methylated nucleosome plasma concentration synergistic information with circulating tumor dna molecular profiling |
| topic | NSCLC epigenetics histone PTM H3K27Me3 nucleosome ctDNA liquid biopsy |
| url | https://www.mdpi.com/2218-273X/13/8/1255 |
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