Serial profiling of cell-free DNA and nucleosome histone modifications in cell cultures

Abstract Recent advances in basic research have unveiled several strategies for improving the sensitivity and specificity of cell-free DNA (cfDNA) based assays, which is a prerequisite for broadening its clinical use. Included among these strategies is leveraging knowledge of both the biogenesis and...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Vida Ungerer, Abel J. Bronkhorst, Priscilla Van den Ackerveken, Marielle Herzog, Stefan Holdenrieder
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3d21f76d3af146979aaf89c988ffa78d
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:3d21f76d3af146979aaf89c988ffa78d
record_format	dspace
spelling	oai:doaj.org-article:3d21f76d3af146979aaf89c988ffa78d2021-12-02T15:37:58ZSerial profiling of cell-free DNA and nucleosome histone modifications in cell cultures10.1038/s41598-021-88866-52045-2322https://doaj.org/article/3d21f76d3af146979aaf89c988ffa78d2021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88866-5https://doaj.org/toc/2045-2322Abstract Recent advances in basic research have unveiled several strategies for improving the sensitivity and specificity of cell-free DNA (cfDNA) based assays, which is a prerequisite for broadening its clinical use. Included among these strategies is leveraging knowledge of both the biogenesis and physico-chemical properties of cfDNA towards the identification of better disease-defining features and optimization of methods. While good progress has been made on this front, much of cfDNA biology remains uncharted. Here, we correlated serial measurements of cfDNA size, concentration and nucleosome histone modifications with various cellular parameters, including cell growth rate, viability, apoptosis, necrosis, and cell cycle phase in three different cell lines. Collectively, the picture emerged that temporal changes in cfDNA levels are rather irregular and not the result of constitutive release from live cells. Instead, changes in cfDNA levels correlated with intermittent cell death events, wherein apoptosis contributed more to cfDNA release in non-cancer cells and necrosis more in cancer cells. Interestingly, the presence of a ~ 3 kbp cfDNA population, which is often deemed to originate from accidental cell lysis or active release, was found to originate from necrosis. High-resolution analysis of this cfDNA population revealed an underlying DNA laddering pattern consisting of several oligo-nucleosomes, identical to those generated by apoptosis. This suggests that necrosis may contribute significantly to the pool of mono-nucleosomal cfDNA fragments that are generally interrogated for cancer mutational profiling. Furthermore, since active steps are often taken to exclude longer oligo-nucleosomes from clinical biospecimens and subsequent assays this raises the question of whether important pathological information is lost.Vida UngererAbel J. BronkhorstPriscilla Van den AckervekenMarielle HerzogStefan HoldenriederNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-20 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Vida Ungerer Abel J. Bronkhorst Priscilla Van den Ackerveken Marielle Herzog Stefan Holdenrieder Serial profiling of cell-free DNA and nucleosome histone modifications in cell cultures
description	Abstract Recent advances in basic research have unveiled several strategies for improving the sensitivity and specificity of cell-free DNA (cfDNA) based assays, which is a prerequisite for broadening its clinical use. Included among these strategies is leveraging knowledge of both the biogenesis and physico-chemical properties of cfDNA towards the identification of better disease-defining features and optimization of methods. While good progress has been made on this front, much of cfDNA biology remains uncharted. Here, we correlated serial measurements of cfDNA size, concentration and nucleosome histone modifications with various cellular parameters, including cell growth rate, viability, apoptosis, necrosis, and cell cycle phase in three different cell lines. Collectively, the picture emerged that temporal changes in cfDNA levels are rather irregular and not the result of constitutive release from live cells. Instead, changes in cfDNA levels correlated with intermittent cell death events, wherein apoptosis contributed more to cfDNA release in non-cancer cells and necrosis more in cancer cells. Interestingly, the presence of a ~ 3 kbp cfDNA population, which is often deemed to originate from accidental cell lysis or active release, was found to originate from necrosis. High-resolution analysis of this cfDNA population revealed an underlying DNA laddering pattern consisting of several oligo-nucleosomes, identical to those generated by apoptosis. This suggests that necrosis may contribute significantly to the pool of mono-nucleosomal cfDNA fragments that are generally interrogated for cancer mutational profiling. Furthermore, since active steps are often taken to exclude longer oligo-nucleosomes from clinical biospecimens and subsequent assays this raises the question of whether important pathological information is lost.
format	article
author	Vida Ungerer Abel J. Bronkhorst Priscilla Van den Ackerveken Marielle Herzog Stefan Holdenrieder
author_facet	Vida Ungerer Abel J. Bronkhorst Priscilla Van den Ackerveken Marielle Herzog Stefan Holdenrieder
author_sort	Vida Ungerer
title	Serial profiling of cell-free DNA and nucleosome histone modifications in cell cultures
title_short	Serial profiling of cell-free DNA and nucleosome histone modifications in cell cultures
title_full	Serial profiling of cell-free DNA and nucleosome histone modifications in cell cultures
title_fullStr	Serial profiling of cell-free DNA and nucleosome histone modifications in cell cultures
title_full_unstemmed	Serial profiling of cell-free DNA and nucleosome histone modifications in cell cultures
title_sort	serial profiling of cell-free dna and nucleosome histone modifications in cell cultures
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/3d21f76d3af146979aaf89c988ffa78d
work_keys_str_mv	AT vidaungerer serialprofilingofcellfreednaandnucleosomehistonemodificationsincellcultures AT abeljbronkhorst serialprofilingofcellfreednaandnucleosomehistonemodificationsincellcultures AT priscillavandenackerveken serialprofilingofcellfreednaandnucleosomehistonemodificationsincellcultures AT marielleherzog serialprofilingofcellfreednaandnucleosomehistonemodificationsincellcultures AT stefanholdenrieder serialprofilingofcellfreednaandnucleosomehistonemodificationsincellcultures
_version_	1718386166472900608

Serial profiling of cell-free DNA and nucleosome histone modifications in cell cultures

Ejemplares similares