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Authors: Haupts, Anna
Vogel, Anne
Foersch, Sebastian
Hartmann, Monika
Maderer, Annett
Wachter, Nicolas
Huber, Tobias
Kneist, Werner
Roth, Wilfried
Lang, Hauke
Moehler, Markus
Hartmann, Nils
Title: Comparative analysis of nuclear and mitochondrial DNA from tissue and liquid biopsies of colorectal cancer patients
Online publication date: 5-Aug-2022
Year of first publication: 2021
Language: english
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.
DDC: 610 Medizin
610 Medical sciences
Institution: Johannes Gutenberg-Universität Mainz
Department: FB 04 Medizin
Place: Mainz
Version: Published version
Publication type: Zeitschriftenaufsatz
License: CC BY
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Journal: Scientific reports
Pages or article number: 16745
Publisher: Macmillan Publishers Limited, part of Springer Nature
Publisher place: London
Issue date: 2021
ISSN: 2045-2322
Publisher DOI: 10.1038/s41598-021-95006-6
Appears in collections:JGU-Publikationen

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