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

被引：16

作者：

van der Pol, Ymke ^{[1
,2
]}

Moldovan, Norbert ^{[1
,2
]}

Ramaker, Jip ^{[1
,2
]}

Bootsma, Sanne ^{[3
,4
,5
]}

Lenos, Kristiaan J. ^{[3
,4
,5
]}

Vermeulen, Louis ^{[3
,4
,5
]}

Sandhu, Shahneen ^{[6
,7
]}

Bahce, Idris ^{[8
]}

Pegtel, D. Michiel ^{[1
,2
]}

Wong, Stephen Q. ^{[6
,7
]}

Dawson, Sarah-Jane ^{[6
,7
,9
]}

Chandrananda, Dineika ^{[6
,7
]}

Mouliere, Florent ^{[1
,2
,10
]}

机构：

[1] Vrije Univ Amsterdam, Amsterdam UMC Locat, Pathol, Amsterdam, Netherlands

[2] Canc Ctr Amsterdam, Imaging & Biomarkers, Amsterdam, Netherlands

[3] Univ Amsterdam, Ctr Expt & Mol Med, Lab Expt Oncol & Radiobiol, Amsterdam UMC Locat, Amsterdam, Netherlands

[4] Canc Ctr Amsterdam, Gastroenterol Endocrinol Metab, Amsterdam, Netherlands

[5] Oncode Inst, Amsterdam, Netherlands

[6] Peter MacCallum Canc Ctr, Melbourne, Australia

[7] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Australia

[8] Vrije Univ Amsterdam, Pulmonol, Amsterdam UMC Locat, Amsterdam, Netherlands

[9] Univ Melbourne, Ctr Canc Res, Melbourne, Australia

[10] Canc Res UK Canc Biomarker Ctr, Manchester, England

来源：

GENOME BIOLOGY | 2023年 / 24卷 / 01期

基金：

澳大利亚国家健康与医学研究理事会;

关键词：

Cell-free DNA; Mitochondrial DNA; Cancer; Sequencing; Liquid biopsy;

D O I：

10.1186/s13059-023-03074-w

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

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.

引用

页数：16

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