Comparative analysis of nuclear and mitochondrial DNA from tissue and liquid biopsies of colorectal cancer patients

Abstract The current standard for molecular profiling of colorectal cancer (CRC) is using resected or biopsied tissue specimens. However, they are limited regarding sampling frequency, representation of tumor heterogeneity, and sampling can expose patients to adverse side effects. The analysis of ce...

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Autores principales:	Anna Haupts, Anne Vogel, Sebastian Foersch, Monika Hartmann, Annett Maderer, Nicolas Wachter, Tobias Huber, Werner Kneist, Wilfried Roth, Hauke Lang, Markus Moehler, Nils Hartmann
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a0ed0fa91b424f0dac5d064546a90fbe
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spelling	oai:doaj.org-article:a0ed0fa91b424f0dac5d064546a90fbe2021-12-02T18:51:47ZComparative analysis of nuclear and mitochondrial DNA from tissue and liquid biopsies of colorectal cancer patients10.1038/s41598-021-95006-62045-2322https://doaj.org/article/a0ed0fa91b424f0dac5d064546a90fbe2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95006-6https://doaj.org/toc/2045-2322Abstract The current standard for molecular profiling of colorectal cancer (CRC) is using resected or biopsied tissue specimens. However, they are limited regarding sampling frequency, representation of tumor heterogeneity, and sampling can expose patients to adverse side effects. The analysis of cell-free DNA (cfDNA) from blood plasma, which is part of a liquid biopsy, is minimally invasive and in principle enables detection of all tumor-specific mutations. Here, we analyzed cfDNA originating from nucleus and mitochondria and investigated their characteristics and mutation status in a cohort of 18 CRC patients and 10 healthy controls using targeted next-generation sequencing (NGS) and digital PCR. Longitudinal analyses of nuclear cfDNA level and size during chemotherapy revealed a decreasing cfDNA content and a shift from short to long fragments, indicating an appropriate therapy response, while shortened cfDNAs and increased cfDNA content corresponded with tumor recurrence. Comparative NGS analysis of nuclear tissue and plasma DNA demonstrated a good patient-level concordance and cfDNA revealed additional variants in three of the cases. Analysis of mitochondrial cfDNA surprisingly revealed a higher plasma copy number in healthy subjects than in CRC patients. These results highlight the potential clinical utility of liquid biopsies in routine diagnostics and surveillance of CRC patients as complementation to tissue biopsies or as an attractive alternative in cases where tissue biopsies are risky or the quantity/quality does not allow testing.Anna HauptsAnne VogelSebastian FoerschMonika HartmannAnnett MadererNicolas WachterTobias HuberWerner KneistWilfried RothHauke LangMarkus MoehlerNils HartmannNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anna Haupts Anne Vogel Sebastian Foersch Monika Hartmann Annett Maderer Nicolas Wachter Tobias Huber Werner Kneist Wilfried Roth Hauke Lang Markus Moehler Nils Hartmann Comparative analysis of nuclear and mitochondrial DNA from tissue and liquid biopsies of colorectal cancer patients
description	Abstract The current standard for molecular profiling of colorectal cancer (CRC) is using resected or biopsied tissue specimens. However, they are limited regarding sampling frequency, representation of tumor heterogeneity, and sampling can expose patients to adverse side effects. The analysis of cell-free DNA (cfDNA) from blood plasma, which is part of a liquid biopsy, is minimally invasive and in principle enables detection of all tumor-specific mutations. Here, we analyzed cfDNA originating from nucleus and mitochondria and investigated their characteristics and mutation status in a cohort of 18 CRC patients and 10 healthy controls using targeted next-generation sequencing (NGS) and digital PCR. Longitudinal analyses of nuclear cfDNA level and size during chemotherapy revealed a decreasing cfDNA content and a shift from short to long fragments, indicating an appropriate therapy response, while shortened cfDNAs and increased cfDNA content corresponded with tumor recurrence. Comparative NGS analysis of nuclear tissue and plasma DNA demonstrated a good patient-level concordance and cfDNA revealed additional variants in three of the cases. Analysis of mitochondrial cfDNA surprisingly revealed a higher plasma copy number in healthy subjects than in CRC patients. These results highlight the potential clinical utility of liquid biopsies in routine diagnostics and surveillance of CRC patients as complementation to tissue biopsies or as an attractive alternative in cases where tissue biopsies are risky or the quantity/quality does not allow testing.
format	article
author	Anna Haupts Anne Vogel Sebastian Foersch Monika Hartmann Annett Maderer Nicolas Wachter Tobias Huber Werner Kneist Wilfried Roth Hauke Lang Markus Moehler Nils Hartmann
author_facet	Anna Haupts Anne Vogel Sebastian Foersch Monika Hartmann Annett Maderer Nicolas Wachter Tobias Huber Werner Kneist Wilfried Roth Hauke Lang Markus Moehler Nils Hartmann
author_sort	Anna Haupts
title	Comparative analysis of nuclear and mitochondrial DNA from tissue and liquid biopsies of colorectal cancer patients
title_short	Comparative analysis of nuclear and mitochondrial DNA from tissue and liquid biopsies of colorectal cancer patients
title_full	Comparative analysis of nuclear and mitochondrial DNA from tissue and liquid biopsies of colorectal cancer patients
title_fullStr	Comparative analysis of nuclear and mitochondrial DNA from tissue and liquid biopsies of colorectal cancer patients
title_full_unstemmed	Comparative analysis of nuclear and mitochondrial DNA from tissue and liquid biopsies of colorectal cancer patients
title_sort	comparative analysis of nuclear and mitochondrial dna from tissue and liquid biopsies of colorectal cancer patients
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a0ed0fa91b424f0dac5d064546a90fbe
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Comparative analysis of nuclear and mitochondrial DNA from tissue and liquid biopsies of colorectal cancer patients

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