Tracing the Origin of Cell-Free DNA Molecules through Tissue-Specific Epigenetic Signatures
All cell and tissue types constantly release DNA fragments into human body fluids by various mechanisms including programmed cell death, accidental cell degradation and active extrusion. Particularly, cell-free DNA (cfDNA) in plasma or serum has been utilized for minimally invasive molecular diagnos...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-07-01
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| Series: | Diagnostics |
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| Online Access: | https://www.mdpi.com/2075-4418/12/8/1834 |
| _version_ | 1797446111711985664 |
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| author | Angela Oberhofer Abel J. Bronkhorst Carsten Uhlig Vida Ungerer Stefan Holdenrieder |
| author_facet | Angela Oberhofer Abel J. Bronkhorst Carsten Uhlig Vida Ungerer Stefan Holdenrieder |
| author_sort | Angela Oberhofer |
| collection | DOAJ |
| description | All cell and tissue types constantly release DNA fragments into human body fluids by various mechanisms including programmed cell death, accidental cell degradation and active extrusion. Particularly, cell-free DNA (cfDNA) in plasma or serum has been utilized for minimally invasive molecular diagnostics. Disease onset or pathological conditions that lead to increased cell death alter the contribution of different tissues to the total pool of cfDNA. Because cfDNA molecules retain cell-type specific epigenetic features, it is possible to infer tissue-of-origin from epigenetic characteristics. Recent research efforts demonstrated that analysis of, e.g., methylation patterns, nucleosome occupancy, and fragmentomics determined the cell- or tissue-of-origin of individual cfDNA molecules. This novel tissue-of origin-analysis enables to estimate the contributions of different tissues to the total cfDNA pool in body fluids and find tissues with increased cell death (pathologic condition), expanding the portfolio of liquid biopsies towards a wide range of pathologies and early diagnosis. In this review, we summarize the currently available tissue-of-origin approaches and point out the next steps towards clinical implementation. |
| first_indexed | 2024-03-09T13:35:32Z |
| format | Article |
| id | doaj.art-e52b4919a9ff48b6bed4a7b1a3995508 |
| institution | Directory Open Access Journal |
| issn | 2075-4418 |
| language | English |
| last_indexed | 2024-03-09T13:35:32Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Diagnostics |
| spelling | doaj.art-e52b4919a9ff48b6bed4a7b1a39955082023-11-30T21:12:42ZengMDPI AGDiagnostics2075-44182022-07-01128183410.3390/diagnostics12081834Tracing the Origin of Cell-Free DNA Molecules through Tissue-Specific Epigenetic SignaturesAngela Oberhofer0Abel J. Bronkhorst1Carsten Uhlig2Vida Ungerer3Stefan Holdenrieder4Munich Biomarker Research Center, Institute of Laboratory Medicine, German Heart Center, Technical University Munich, Lazarettstraße 36, D-80636 Munich, GermanyMunich Biomarker Research Center, Institute of Laboratory Medicine, German Heart Center, Technical University Munich, Lazarettstraße 36, D-80636 Munich, GermanyMunich Biomarker Research Center, Institute of Laboratory Medicine, German Heart Center, Technical University Munich, Lazarettstraße 36, D-80636 Munich, GermanyMunich Biomarker Research Center, Institute of Laboratory Medicine, German Heart Center, Technical University Munich, Lazarettstraße 36, D-80636 Munich, GermanyMunich Biomarker Research Center, Institute of Laboratory Medicine, German Heart Center, Technical University Munich, Lazarettstraße 36, D-80636 Munich, GermanyAll cell and tissue types constantly release DNA fragments into human body fluids by various mechanisms including programmed cell death, accidental cell degradation and active extrusion. Particularly, cell-free DNA (cfDNA) in plasma or serum has been utilized for minimally invasive molecular diagnostics. Disease onset or pathological conditions that lead to increased cell death alter the contribution of different tissues to the total pool of cfDNA. Because cfDNA molecules retain cell-type specific epigenetic features, it is possible to infer tissue-of-origin from epigenetic characteristics. Recent research efforts demonstrated that analysis of, e.g., methylation patterns, nucleosome occupancy, and fragmentomics determined the cell- or tissue-of-origin of individual cfDNA molecules. This novel tissue-of origin-analysis enables to estimate the contributions of different tissues to the total cfDNA pool in body fluids and find tissues with increased cell death (pathologic condition), expanding the portfolio of liquid biopsies towards a wide range of pathologies and early diagnosis. In this review, we summarize the currently available tissue-of-origin approaches and point out the next steps towards clinical implementation.https://www.mdpi.com/2075-4418/12/8/1834cell-free DNAepigeneticsliquid biopsytissue-of-origin |
| spellingShingle | Angela Oberhofer Abel J. Bronkhorst Carsten Uhlig Vida Ungerer Stefan Holdenrieder Tracing the Origin of Cell-Free DNA Molecules through Tissue-Specific Epigenetic Signatures Diagnostics cell-free DNA epigenetics liquid biopsy tissue-of-origin |
| title | Tracing the Origin of Cell-Free DNA Molecules through Tissue-Specific Epigenetic Signatures |
| title_full | Tracing the Origin of Cell-Free DNA Molecules through Tissue-Specific Epigenetic Signatures |
| title_fullStr | Tracing the Origin of Cell-Free DNA Molecules through Tissue-Specific Epigenetic Signatures |
| title_full_unstemmed | Tracing the Origin of Cell-Free DNA Molecules through Tissue-Specific Epigenetic Signatures |
| title_short | Tracing the Origin of Cell-Free DNA Molecules through Tissue-Specific Epigenetic Signatures |
| title_sort | tracing the origin of cell free dna molecules through tissue specific epigenetic signatures |
| topic | cell-free DNA epigenetics liquid biopsy tissue-of-origin |
| url | https://www.mdpi.com/2075-4418/12/8/1834 |
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