The size of cell-free mitochondrial DNA in blood is inversely correlated with tumor burden in cancer patients

被引:29
作者
An, Qin [1 ]
Hu, Youjin [1 ]
Li, Qingjiao [2 ]
Chen, Xufeng [2 ,3 ]
Huang, Jiaoti [2 ,3 ]
Pellegrini, Matteo [4 ]
Zhou, Xianghong Jasmine [2 ]
Rettig, Matthew [5 ]
Fan, Guoping [1 ]
机构
[1] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA
[2] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA
[3] Duke Univ, Sch Med, Dept Pathol, Durham, NC 27710 USA
[4] Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA
[5] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA
基金
美国国家卫生研究院;
关键词
circulating cell-free DNA (cfDNA); tumor burden; cancer progression; liquid biopsy;
D O I
10.1093/pcmedi/pbz014
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Circulating cell-free DNAs (cfDNAs) are fragmented DNA molecules released into the blood by cells. Previous studies have suggested that mitochondria-originated cfDNA fragments (mt-cfDNAs) in cancer patients are more fragmented than those from healthy controls. However, it is still unknown where these short mt-cfDNAs originate, and whether the length of mt-cfDNAs can be correlated with tumor burden and cancer progression. In this study, we first performed whole-genome sequencing analysis (WGS) of cfDNAs from a human tumor cell line-xenotransplantation mouse model and found that mt-cfDNAs released from transplanted tumor cells were shorter than the mouse counterpart. We next analyzed blood cfDNA samples from hepatocellular carcinoma and prostate cancer patients and found that mt-cfDNA lengths were inversely related to tumor size as well as the concentration of circulating tumor DNA. Our study suggested that monitoring the size of mt-cfDNAs in cancer patients would be a useful way to estimate tumor burden and cancer progression.
引用
收藏
页码:131 / 139
页数:9
相关论文
共 27 条
[1]   Exome Sequencing of Cell-Free DNA from Metastatic Cancer Patients Identifies Clinically Actionable Mutations Distinct from Primary Disease [J].
Butler, Timothy M. ;
Johnson-Camacho, Katherine ;
Peto, Myron ;
Wang, Nicholas J. ;
Macey, Tara A. ;
Korkola, James E. ;
Koppie, Theresa M. ;
Corless, Christopher L. ;
Gray, Joe W. ;
Spellman, Paul T. .
PLOS ONE, 2015, 10 (08)
[2]   Genome-wide cell-free DNA fragmentation in patients with cancer [J].
Cristiano, Stephen ;
Leal, Alessandro ;
Phallen, Jillian ;
Fiksel, Jacob ;
Adleff, Vilmos ;
Bruhm, Daniel C. ;
Jensen, Sarah Ostrup ;
Medina, Jamie E. ;
Hruban, Carolyn ;
White, James R. ;
Palsgrove, Doreen N. ;
Niknafs, Noushin ;
Anagnostou, Valsamo ;
Forde, Patrick ;
Naidoo, Jarushka ;
Marrone, Kristen ;
Brahmer, Julie ;
Woodward, Brian D. ;
Husain, Hatim ;
van Rooijen, Karlijn L. ;
Orntoft, Mai-Britt Worm ;
Madsen, Anders Husted ;
van de Velde, Cornelis J. H. ;
Verheij, Marcel ;
Cats, Annemieke ;
Punt, Cornelis J. A. ;
Vink, Geraldine R. ;
van Grieken, Nicole C. T. ;
Koopman, Miriam ;
Fijneman, Remond J. A. ;
Johansen, Julia S. ;
Nielsen, Hans Jorgen ;
Meijer, Gerrit A. ;
Andersen, Claus Lindbjerg ;
Scharpf, Robert B. ;
Velculescu, Victor E. .
NATURE, 2019, 570 (7761) :385-+
[3]   Circulating mitochondrial DNA in serum: A universal diagnostic biomarker for patients with urological malignancies [J].
Ellinger, Joerg ;
Mueller, David C. ;
Mueller, Stefan C. ;
Hauser, Stefan ;
Heukamp, Lukas C. ;
von Ruecker, Alexander ;
Bastian, Patrick J. ;
Walgenbach-Brunagel, Gisela .
UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS, 2012, 30 (04) :509-515
[4]   Tumor-associated copy number changes in the circulation of patients with prostate cancer identified through whole-genome sequencing [J].
Heitzer, Ellen ;
Ulz, Peter ;
Belic, Jelena ;
Gutschi, Stefan ;
Quehenberger, Franz ;
Fischereder, Katja ;
Benezeder, Theresa ;
Auer, Martina ;
Pischler, Carina ;
Mannweiler, Sebastian ;
Pichler, Martin ;
Eisner, Florian ;
Haeusler, Martin ;
Riethdorf, Sabine ;
Pantel, Klaus ;
Samonigg, Hellmut ;
Hoefler, Gerald ;
Augustin, Herbert ;
Geigl, Jochen B. ;
Speicher, Michael R. .
GENOME MEDICINE, 2013, 5
[5]   The Long and Short of Circulating Cell-Free DNA and the Ins and Outs of Molecular Diagnostics [J].
Jiang, Peiyong ;
Lo, Y. M. Dennis .
TRENDS IN GENETICS, 2016, 32 (06) :360-371
[6]   Lengthening and shortening of plasma DNA in hepatocellular carcinoma patients [J].
Jiang, Peiyong ;
Chan, Carol W. M. ;
Chan, K. C. Allen ;
Cheng, Suk Hang ;
Wong, John ;
Wong, Vincent Wai-Sun ;
Wong, Grace L. H. ;
Chan, Stephen L. ;
Mok, Tony S. K. ;
Chan, Henry L. Y. ;
Lai, Paul B. S. ;
Chiu, Rossa W. K. ;
Lo, Y. M. Dennis .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2015, 112 (11) :E1317-E1325
[7]   CancerLocator: non-invasive cancer diagnosis and tissue-of-origin prediction using methylation profiles of cell-free DNA [J].
Kang, Shuli ;
Li, Qingjiao ;
Chen, Quan ;
Zhou, Yonggang ;
Park, Stacy ;
Lee, Gina ;
Grimes, Brandon ;
Krysan, Kostyantyn ;
Yu, Min ;
Wang, Wei ;
Alber, Frank ;
Sun, Fengzhu ;
Dubinett, Steven M. ;
Li, Wenyuan ;
Zhou, Xianghong Jasmine .
GENOME BIOLOGY, 2017, 18
[8]   Bismark: a flexible aligner and methylation caller for Bisulfite-Seq applications [J].
Krueger, Felix ;
Andrews, Simon R. .
BIOINFORMATICS, 2011, 27 (11) :1571-1572
[9]   AR intragenic deletions linked to androgen receptor splice variant expression and activity in models of prostate cancer progression [J].
Li, Y. ;
Hwang, T. H. ;
Oseth, L. A. ;
Hauge, A. ;
Vessella, R. L. ;
Schmechel, S. C. ;
Hirsch, B. ;
Beckman, K. B. ;
Silverstein, K. A. ;
Dehm, S. M. .
ONCOGENE, 2012, 31 (45) :4759-4767
[10]   Maternal Plasma DNA Sequencing Reveals the Genome-Wide Genetic and Mutational Profile of the Fetus [J].
Lo, Y. M. Dennis ;
Chan, K. C. Allen ;
Sun, Hao ;
Chen, Eric Z. ;
Jiang, Peiyong ;
Lun, Fiona M. F. ;
Zheng, Yama W. ;
Leung, Tak Y. ;
Lau, Tze K. ;
Cantor, Charles R. ;
Chiu, Rossa W. K. .
SCIENCE TRANSLATIONAL MEDICINE, 2010, 2 (61)