Please use this identifier to cite or link to this item:
http://doi.org/10.25358/openscience-7523
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 |
ROR: | https://ror.org/023b0x485 |
DOI: | http://doi.org/10.25358/openscience-7523 |
Version: | Published version |
Publication type: | Zeitschriftenaufsatz |
License: | CC BY |
Information on rights of use: | https://creativecommons.org/licenses/by/4.0/ |
Journal: | Scientific reports 11 |
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 |
Files in This Item:
File | Description | Size | Format | ||
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comparative_analysis_of_nucle-20220805121812382.pdf | 1.83 MB | Adobe PDF | View/Open |