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The landscape of cell-free mitochondrial DNA in liquid biopsy for cancer detection

BACKGROUND: Existing methods to detect tumor signal in liquid biopsy have focused on the analysis of nuclear cell-free DNA (cfDNA). However, non-nuclear cfDNA and in particular mitochondrial DNA (mtDNA) has been understudied. We hypothesize that an increase in mtDNA in plasma could reflect the prese...

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Autores principales: van der Pol, Ymke, Moldovan, Norbert, Ramaker, Jip, Bootsma, Sanne, Lenos, Kristiaan J., Vermeulen, Louis, Sandhu, Shahneen, Bahce, Idris, Pegtel, D. Michiel, Wong, Stephen Q., Dawson, Sarah-Jane, Chandrananda, Dineika, Mouliere, Florent
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10571306/
https://www.ncbi.nlm.nih.gov/pubmed/37828498
http://dx.doi.org/10.1186/s13059-023-03074-w
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author van der Pol, Ymke
Moldovan, Norbert
Ramaker, Jip
Bootsma, Sanne
Lenos, Kristiaan J.
Vermeulen, Louis
Sandhu, Shahneen
Bahce, Idris
Pegtel, D. Michiel
Wong, Stephen Q.
Dawson, Sarah-Jane
Chandrananda, Dineika
Mouliere, Florent
author_facet van der Pol, Ymke
Moldovan, Norbert
Ramaker, Jip
Bootsma, Sanne
Lenos, Kristiaan J.
Vermeulen, Louis
Sandhu, Shahneen
Bahce, Idris
Pegtel, D. Michiel
Wong, Stephen Q.
Dawson, Sarah-Jane
Chandrananda, Dineika
Mouliere, Florent
author_sort van der Pol, Ymke
collection PubMed
description BACKGROUND: Existing methods to detect tumor signal in liquid biopsy have focused on the analysis of nuclear cell-free DNA (cfDNA). However, non-nuclear cfDNA and in particular mitochondrial DNA (mtDNA) has been understudied. We hypothesize that an increase in mtDNA in plasma could reflect the presence of cancer, and that leveraging cell-free mtDNA could enhance cancer detection. RESULTS: We survey 203 healthy and 664 cancer plasma samples from three collection centers covering 12 cancer types with whole genome sequencing to catalogue the plasma mtDNA fraction. The mtDNA fraction is increased in individuals with cholangiocarcinoma, colorectal, liver, pancreatic, or prostate cancer, in comparison to that in healthy individuals. We detect almost no increase of mtDNA fraction in individuals with other cancer types. The mtDNA fraction in plasma correlates with the cfDNA tumor fraction as determined by somatic mutations and/or copy number aberrations. However, the mtDNA fraction is also elevated in a fraction of patients without an apparent increase in tumor-derived cfDNA. A predictive model integrating mtDNA and copy number analysis increases the area under the curve (AUC) from 0.73 when using copy number alterations alone to an AUC of 0.81. CONCLUSIONS: The mtDNA signal retrieved by whole genome sequencing has the potential to boost the detection of cancer when combined with other tumor-derived signals in liquid biopsies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13059-023-03074-w.
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spelling pubmed-105713062023-10-14 The landscape of cell-free mitochondrial DNA in liquid biopsy for cancer detection van der Pol, Ymke Moldovan, Norbert Ramaker, Jip Bootsma, Sanne Lenos, Kristiaan J. Vermeulen, Louis Sandhu, Shahneen Bahce, Idris Pegtel, D. Michiel Wong, Stephen Q. Dawson, Sarah-Jane Chandrananda, Dineika Mouliere, Florent Genome Biol Research BACKGROUND: Existing methods to detect tumor signal in liquid biopsy have focused on the analysis of nuclear cell-free DNA (cfDNA). However, non-nuclear cfDNA and in particular mitochondrial DNA (mtDNA) has been understudied. We hypothesize that an increase in mtDNA in plasma could reflect the presence of cancer, and that leveraging cell-free mtDNA could enhance cancer detection. RESULTS: We survey 203 healthy and 664 cancer plasma samples from three collection centers covering 12 cancer types with whole genome sequencing to catalogue the plasma mtDNA fraction. The mtDNA fraction is increased in individuals with cholangiocarcinoma, colorectal, liver, pancreatic, or prostate cancer, in comparison to that in healthy individuals. We detect almost no increase of mtDNA fraction in individuals with other cancer types. The mtDNA fraction in plasma correlates with the cfDNA tumor fraction as determined by somatic mutations and/or copy number aberrations. However, the mtDNA fraction is also elevated in a fraction of patients without an apparent increase in tumor-derived cfDNA. A predictive model integrating mtDNA and copy number analysis increases the area under the curve (AUC) from 0.73 when using copy number alterations alone to an AUC of 0.81. CONCLUSIONS: The mtDNA signal retrieved by whole genome sequencing has the potential to boost the detection of cancer when combined with other tumor-derived signals in liquid biopsies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13059-023-03074-w. BioMed Central 2023-10-12 /pmc/articles/PMC10571306/ /pubmed/37828498 http://dx.doi.org/10.1186/s13059-023-03074-w Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
van der Pol, Ymke
Moldovan, Norbert
Ramaker, Jip
Bootsma, Sanne
Lenos, Kristiaan J.
Vermeulen, Louis
Sandhu, Shahneen
Bahce, Idris
Pegtel, D. Michiel
Wong, Stephen Q.
Dawson, Sarah-Jane
Chandrananda, Dineika
Mouliere, Florent
The landscape of cell-free mitochondrial DNA in liquid biopsy for cancer detection
title The landscape of cell-free mitochondrial DNA in liquid biopsy for cancer detection
title_full The landscape of cell-free mitochondrial DNA in liquid biopsy for cancer detection
title_fullStr The landscape of cell-free mitochondrial DNA in liquid biopsy for cancer detection
title_full_unstemmed The landscape of cell-free mitochondrial DNA in liquid biopsy for cancer detection
title_short The landscape of cell-free mitochondrial DNA in liquid biopsy for cancer detection
title_sort landscape of cell-free mitochondrial dna in liquid biopsy for cancer detection
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10571306/
https://www.ncbi.nlm.nih.gov/pubmed/37828498
http://dx.doi.org/10.1186/s13059-023-03074-w
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