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Review

Life and death of circulating cell-free DNA

, , &
Pages 1057-1067 | Received 28 Nov 2018, Accepted 12 Mar 2019, Published online: 16 Apr 2019

References

  • Nehmat H, Nehmat H. Overdiagnosis of breast cancer in population screening: does it make breast screening worthless? Cancer Biol Med. 2017;14(1):1–8. doi:10.20892/j.issn.2095-3941.2016.0050.
  • Autier P, Boniol M, Koechlin A, Pizot C, Boniol M. Effectiveness of and overdiagnosis from mammography screening in the Netherlands: population based study. Bmj. 2017;j5224. doi:10.1136/bmj.j5224.
  • Salvi S, Gurioli G, De Giorgi U, Conteduca V, Tedaldi G, Calistri D, Casadio V. Cell-free DNA as a diagnostic marker for cancer: current insights. Onco Targets Ther. 2016;9:6549–6559. doi:10.2147/OTT.S100901.
  • Donaldson J, Bh P. Circulating tumor DNA: measurement and clinical utility. Annu Rev Med. 2018;69(1):1–512. doi:10.1146/annurev-med-041316-085721.
  • Bellairs JA, Hasina R, Agrawal N. Tumor DNA: an emerging biomarker in head and neck cancer. Cancer Metastasis Rev. 2017;36(3):515–523. doi:10.1007/s10555-017-9685-x.
  • Crowley E, Di Nicolantonio F, Loupakis F, Bardelli A. Liquid biopsy: monitoring cancer-genetics in the blood. Nat Rev Clin Oncol. 2013;10(8):472–484. doi:10.1038/nrclinonc.2013.110.
  • Schwarzenbach H, Hoon DSB, Pantel K. Cell-free nucleic acids as biomarkers in cancer patients. Nat Rev Cancer. 2011;11(6):426–437. doi:10.1038/nrc3066.
  • Lipinski KA, Barber LJ, Davies MN, Ashenden M, Sottoriva A, Gerlinger M. Cancer evolution and the limits of predictability in precision cancer medicine. Trends in Cancer. 2016;2(1):49–63. doi:10.1016/j.trecan.2015.11.003.
  • Bennett CW, Berchem G, Kim YJ, El-Khoury V. Cell-free DNA and next-generation sequencing in the service of personalized medicine for lung cancer. Oncotarget. 2015;7(September):71013–71035. doi:10.18632/oncotarget.11717.
  • Rapisuwon S, Vietsch EE, Wellstein A. Circulating biomarkers to monitor cancer progression and treatment. Comput Struct Biotechnol J. 2016;14:211–222. doi:10.1016/j.csbj.2016.05.004.
  • Siravegna G, Marsoni S, Siena S, Bardelli A. Integrating liquid biopsies into the management of cancer. Nat Rev Clin Oncol. 2017;14(9):531–548. doi:10.1038/nrclinonc.2017.14.
  • Chen Y, Guo W, Fan J, et al. The applications of liquid biopsy in resistance surveillance of anaplastic lymphoma kinase inhibitor. Cancer Manag Res. 2017;9:801–811. doi:10.2147/CMAR.S151235.
  • Thiele J-A, Bethel K, Králíčková M, Kuhn P. Circulating tumor cells: fluid surrogates of solid tumors. Annu Rev Pathol Mech Dis. 2017;12(1):419–447. doi:10.1146/annurev-pathol-052016-100256.
  • Kowalik A, Kowalewska M, Góźdź S. Current approaches for avoiding the limitations of circulating tumor cells detection methods—implications for diagnosis and treatment of patients with solid tumors. Transl Res. 2017;185:58–84.e15. doi:10.1016/j.trsl.2017.04.002.
  • Endzelinš E, Berger A, Melne V, et al. Detection of circulating miRNAs: comparative analysis of extracellular vesicle-incorporated miRNAs and cell-free miRNAs in whole plasma of prostate cancer patients. BMC Cancer. 2017;17(1):1–13. doi:10.1186/s12885-017-3737-z.
  • Ma X, Zhu L, Wu X, et al. Cell-free DNA provides a good representation of the tumor genome despite its biased fragmentation patterns. PLoS One. 2017;12(1):1–18. doi:10.1371/journal.pone.0169231.
  • Garcia-Romero N, Esteban-Rubio S, Rackov G, Carrión-Navarro J, Belda-Iniesta C, Ayuso-Sacido A. Extracellular vesicles compartment in liquid biopsies: clinical application. Mol Aspects Med. 2017;60:27–37. doi:10.1016/j.mam.2017.11.009.
  • McAnena P, Brown JAL, Kerin MJ. Circulating nucleosomes and nucleosome modifications as biomarkers in cancer. Cancers (Basel). 2017;9(1):5. doi:10.3390/cancers9010005.
  • Rahier JF, Druez A, Faugeras L, et al. Circulating nucleosomes as new blood-based biomarkers for detection of colorectal cancer. Clin Epigenetics. 2017;9(1):1–7. doi:10.1186/s13148-017-0351-5.
  • Schwarzenbach H. Clinical relevance of circulating, cell-free and exosomal microRNAs in plasma and serum of breast cancer patients. Oncol Res Treat. 2017;40:423–429. doi:10.1159/000478019.
  • Palmirotta R, Lovero D, Cafforio P, Felici C, Mannavola F, Pellè E, Quaresmini D, Tucci M, Silvestris F. Liquid biopsy of cancer: a multimodal diagnostic tool in clinical oncology. Ther Adv Med Oncol. 2018;10:1–24. doi:10.1177/1758835918794630.
  • Lo YMD, Lam WKJ. Tracing the tissue of origin of plasma DNA—feasibility and implications. Ann N Y Acad Sci. 2016;1376(1):14–17. doi:10.1111/nyas.13163.
  • Tie J, Wang Y, Tomasetti C, et al. Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer. Sci Transl Med. 2016;8(346):346ra92. doi:10.1126/scitranslmed.aaf6219.Circulating.
  • Thierry AR, El Messaoudi S, Gahan PB, Anker P, Stroun M. Origins, structures, and functions of circulating DNA in oncology. Cancer Metastasis Rev. 2016;35(3):347–376. doi:10.1007/s10555-016-9629-x.
  • Muhanna N, Di Grappa MA, Chan HHL, Khan T, Jin CS, Zheng Y, Irish JC, Bratman SV. Cell-free DNA kinetics in a pre-clinical model of head and neck cancer. Sci Rep. 2017;7(1):16723. doi:10.1038/s41598-017-17079-6.
  • Bartels S, Persing S, Hasemeier B, Schipper E, Kreipe H, Lehmann U. Molecular analysis of circulating free DNA from lung cancer patients in routine laboratory practice. J Mol Diagnostics. 2017;19(5):722–732. doi:10.1016/j.jmoldx.2017.05.008.
  • Heitzer E, Haque IS, Roberts CE, Speicher MR. Current and future perspectives of liquid biopsies in genomics-driven oncology. Nat Rev Genet. doi:10.1038/s41576-018-0071-5.
  • Corcoran RB, Chabner BA. Application of cell-free DNA analysis to cancer treatment. N Engl J Med. 2018;379:1754–1765. doi:10.1056/NEJMra1706174.
  • Merker JD, Oxnard GR, Compton C, et al. Circulating tumor DNA analysis in patients with cancer: American Society of Clinical Oncology and College of American Pathologists joint review. J Clin Oncol. 2018;JCO.2017.76.867. doi:10.1200/JCO.2017.76.8671.
  • Mandel P, Metais P. Les acides nucléiques du plasma sanguin chez l’homme. C R Seances Soc Biol Ses Fil. 1948. doi:10.1007/BF00832140.
  • Leon SA, Shapiro B, Sklaroff DM, et al. Free DNA in the serum of cancer patients and the effect of therapy free DNA in the serum of cancer patients and the effect of therapy. Cancer Res. 1977;37(March):646–650.
  • Zhu YJ, Zhang HB, Liu YH, Zhang F-L, Zhu Y-Z, Li Y, Bai J-P, Liu L-R, Qu Y-C, Qu X, et al. Quantitative cell-free circulating EGFR mutation concentration is correlated with tumor burden in advanced NSCLC patients. Lung Cancer. 2017;109(March):124–127. doi:10.1016/j.lungcan.2017.05.005.
  • Sharon E, Shi H, Kharbanda S, et al. Quantification of transplant-derived circulating cell-free DNA in absence of a donor genotype. PLoS Comput Biol. 2017;13(8):e1005629. doi:10.1371/journal.pcbi.1005629.
  • Burnham P, Khush K, De Vlaminck I. Myriad applications of circulating cell-free DNA in precision organ transplant monitoring. Ann Am Thorac Soc. 2017;14(7):S237–S241. doi:10.1513/AnnalsATS.201608-634MG.
  • Tug S, Helmig S, Deichmann ER, Schmeier-Jürchott A, Wagner E, Zimmermann T, Radsak M, Giacca M, Simon P. Exercise-induced increases in cell free DNA in human plasma originate predominantly from cells of the haematopoietic lineage. Exerc Immunol Rev. 2015;21(27):164–173.
  • Breitbach S, Tug S, Helmig S, Zahn D, Kubiak T, Michal M, Gori T, Ehlert T, Beiter T, Simon P, et al. Direct quantification of cell-free, circulating DNA from unpurified plasma. PLoS One. 2014;9(3):e87838. doi:10.1371/journal.pone.0087838.
  • O’Connell GC, Petrone AB, Tennant CS, Lucke-Wold N, Kabbani Y, Tarabishy AR, Chantler PD, Barr TL. Circulating extracellular DNA levels are acutely elevated in ischaemic stroke and associated with innate immune system activation. Brain Inj. 2017;31(10):1369–1375. doi:10.1080/02699052.2017.1312018.
  • Wilson IJ, Burchell RK, Worth AJ, Burton SE, Gedye KR, Clark KJ, Crosse KR, Jack M, Odom TF, De Grey SJ, et al. Kinetics of plasma cell-free DNA and creatine kinase in a canine model of tissue injury. J Vet Intern Med. 2017;32(1):157–164. doi:10.1111/jvim.14901.
  • Volik S, Alcaide M, Morin RD, Collins C. Cell-free DNA (cfDNA): clinical significance and utility in cancer shaped by emerging technologies. Mol Cancer Res. 2016;14(10):898–908. doi:10.1158/1541-7786.MCR-16-0044.
  • Zill OA, Banks KC, Fairclough SR, Mortimer SA, Vowles JV, Mokhtari R, Gandara DR, Mack PC, Odegaard JI, Nagy RJ, et al. The landscape of actionable genomic alterations in cell-free circulating tumor DNA from 21,807 advanced cancer patients. Clinical Cancer Res. 2018;24:3528–3538. doi:10.1158/1078-0432.CCR-17-3837.
  • Bettegowda C, Sausen M, Leary R, Kinde I, Wang Y, Agrawal N, Bartlett BR, Wang H, Luber B, Alani RM, et al. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med. 2014;6(224):224ra24. doi:10.1126/scitranslmed.3007094.Detection.
  • Khier S, Lohan L. Kinetics of circulating cell-free DNA for biomedical applications: critical appraisal of the literature. Future Sci OA. 2018;4:FSO295. doi:10.4155/fsoa-2017-0140.
  • Myint NNM, Verma AM, Fernandez-Garcia D, et al. Circulating tumor DNA in patients with colorectal adenomas: assessment of detectability and genetic heterogeneity. Cell Death Dis. 2018;9(9):894. doi:10.1038/s41419-018-0934-x.
  • Diehl F, Li M, Dressman D, He Y, Shen D, Szabo S, Diaz LA, Goodman SN, David KA, Juhl H, et al. Detection and quantification of mutations in the plasma of patients with colorectal tumors. Proc Natl Acad Sci. 2005;102(45):16368–16373. doi:10.1073/pnas.0507904102.
  • Xia L, Li Z, Zhou B, et al. Statistical analysis of mutant allele frequency level of circulating cell-free DNA and blood cells in healthy individuals. Sci Rep. 2017;7(1):1–7. doi:10.1038/s41598-017-06106-1.
  • Valpione S, Gremel G, Mundra P, Middlehurst P, Galvani E, Girotti MR, Lee RJ, Garner G, Dhomen N, Lorigan PC, et al. Plasma total cell-free DNA (cfDNA) is a surrogate biomarker for tumour burden and a prognostic biomarker for survival in metastatic melanoma patients. Eur J Cancer. 2018;88:1–9. doi:10.1016/j.ejca.2017.10.029.
  • Winther-Larsen A, Demuth C, Fledelius J, Madsen AT, Hjorthaug K, Meldgaard P, Sorensen BS. Correlation between circulating mutant DNA and metabolic tumour burden in advanced non-small cell lung cancer patients. Br J Cancer. 2017;117(5):704–709. doi:10.1038/bjc.2017.215.
  • Morbelli S, Alama A, Ferrarazzo G, et al. Circulating tumor DNA reflects tumor metabolism rather than tumor burden in chemotherapy-naive patients with advanced non-small cell lung cancer (NSCLC): an 18 F-FDG PET/CT study. J Nucl Med. 2017;58(11):jnumed.117.193201. doi:10.2967/jnumed.117.193201.
  • Wong SQ, Raleigh JM, Callahan J, et al. Circulating tumor DNA analysis and functional imaging provide complementary approaches for comprehensive disease monitoring in metastatic melanoma. JCO Precis Oncol. 2017;(1):1–14. doi:10.1200/PO.16.00009.
  • Mcevoy AC, Warburton L, Al-Ogaili Z, et al. Correlation between circulating tumour DNA and metabolic tumour burden in metastatic melanoma patients. 2018;1–8.
  • Cohen JD, Li L, Wang Y, Thoburn C, Afsari B, Danilova L, Douville C, Javed AA, Wong F, Mattox A, et al. Detection and localization of surgically resectable cancers with a multi-analyte blood test. Science (80-). 2018;359(6378):926–930. doi:10.1126/science.aar3247.
  • Lehmann-Werman R, Neiman D, Zemmour H, Moss J, Magenheim J, Vaknin-Dembinsky A, Rubertsson S, Nellgård B, Blennow K, Zetterberg H, et al. Identification of tissue-specific cell death using methylation patterns of circulating DNA. Proc Natl Acad Sci. 2016;113(13):E1826–E1834. doi:10.1073/pnas.1519286113.
  • Wu DC, Lambowitz AM. Facile single-stranded DNA sequencing of human plasma DNA via thermostable group II intron reverse transcriptase template switching OPEN. doi:10.1038/s41598-017-09064-w.
  • Moss J, Magenheim J, Neiman D, Zemmour H, Loyfer N, Korach A, Samet Y, Maoz M, Druid H, Arner P, et al. Comprehensive human cell-type methylation atlas reveals origins of circulating cell-free DNA in health and disease. Nat Commun. 2018;9(1):5068. doi:10.1038/s41467-018-07466-6.
  • Wong FCK, Sun K, Jiang P, Cheng YKY, Chan KCA, Leung TY, Chiu RWK, Lo YMD. Cell-free DNA in maternal plasma and serum: a comparison of quantity, quality and tissue origin using genomic and epigenomic approaches. Clin Biochem. 2016;49(18):1379–1386. doi:10.1016/j.clinbiochem.2016.09.009.
  • Snyder MW, Kircher M, Hill AJ, Daza RM, Shendure J. Cell-free DNA comprises an in vivo nucleosome footprint that informs its tissues-of-origin. Cell. 2016;164(1–2):57–68. doi:10.1016/j.cell.2015.11.050.Cell-free.
  • Ivanov M, Baranova A, Butler T, Spellman P, Mileyko V. Non-random fragmentation patterns in circulating cell-free DNA reflect epigenetic regulation. BMC Genomics. 2015;16(13):1–12. doi:10.1186/1471-2164-16-S13-S1.
  • Zhang W, Xia W, Lv Z, Ni C, Xin Y, Yang L. Liquid biopsy for cancer: circulating tumor cells, circulating free DNA or exosomes? Cell Physiol Biochem. 2017;41(2):755–768. doi:10.1159/000458736.
  • Neumann MHD, Bender S, Krahn T, Schlange T. ctDNA and CTCs in liquid biopsy – current status and where we need to progress. Comput Struct Biotechnol J. 2018;16:190–195. doi:10.1016/J.CSBJ.2018.05.002.
  • Murtaza M, Dawson SJ, Pogrebniak K, Rueda OM, Provenzano E, Grant J, Chin S-F, Tsui DWY, Marass F, Gale D, et al. Multifocal clonal evolution characterized using circulating tumour DNA in a case of metastatic breast cancer. Nat Commun. 2015;6:1–6. doi:10.1038/ncomms9760.
  • Mouliere F, Thierry AR. The importance of examining the proportion of circulating DNA originating from tumor, microenvironment and normal cells in colorectal cancer patients. Expert Opin Biol Ther. 2012;12(sup1):S209–S215. doi:10.1517/14712598.2012.688023.
  • Ulz P, Thallinger GG, Auer M, Graf R, Kashofer K, Jahn SW, Abete L, Pristauz G, Petru E, Geigl JB, et al. Inferring expressed genes by whole-genome sequencing of plasma DNA. Nat Genet. 2016;48(10):1273–1278. doi:10.1038/ng.3648.
  • Lam WKJ, Gai W, Sun K, Wong RSM, Chan RWY, Jiang P, Chan NPH, Hui WWI, Chan AWH, Szeto -C-C, et al. DNA of erythroid origin is present in human plasma and informs the types of anemia. Clin Chem. 2017;63:1614–1623. doi:10.1373/clinchem.2017.272401.
  • Fleischhacker M, Schmidt B. Circulating nucleic acids (CNAs) and cancer: a survey. Biochim Biophys Acta - Rev Cancer. 2007;1775(1):181–232. doi:10.1016/j.bbcan.2006.10.001.
  • Jiang P, Chan CWM, Chan KCA, et al. Lengthening and shortening of plasma DNA in hepatocellular carcinoma patients. Proc Natl Acad Sci. 2015;112(11):E1317–E1325. doi:10.1073/pnas.1500076112.
  • Kumar M, Srivastava S, Singh SA, Das AK, Das GC, Dhar B, Ghosh SK, Mondal R. Cell-free mitochondrial DNA copy number variation in head and neck squamous cell carcinoma: a study of non-invasive biomarker from Northeast India. Tumor Biol. 2017;39(10):1–9. doi:10.1177/1010428317736643.
  • Fernandes J, Michel V, Camorlinga-Ponce M, Gomez A, Maldonado C, De Reuse H, Torres J, Touati E. Circulating mitochondrial DNA level, a noninvasive biomarker for the early detection of gastric cancer. Cancer Epidemiol Biomarkers Prev. 2014;23(11):2430–2438. doi:10.1158/1055-9965.EPI-14-0471.
  • Holdenrieder S, Nagel D, Schalhorn A, Heinemann V, Wilkowski R, von Pawel J, Raith H, Feldmann K, Kremer AE, Müller S, et al. Clinical relevance of circulating nucleosomes in cancer. Ann N Y Acad Sci. 2008;1137:180–189. doi:10.1196/annals.1448.012.
  • Torralba D, Baixauli F, Villarroya-Beltri C, et al. Priming of dendritic cells by DNA-containing extracellular vesicles from activated T cells through antigen-driven contacts. Nat Commun. 2018;9(1):1–17. doi:10.1038/s41467-018-05077-9.
  • Fernando MR, Jiang C, Krzyzanowski GD, Ryan WL. New evidence that a large proportion of human blood plasma cell-free DNA is localized in exosomes. PLoS One. 2017;12(8):1–15. doi:10.1371/journal.pone.0183915.
  • Vagner T, Spinelli C, Minciacchi VR, Balaj L, Zandian M, Conley A, Zijlstra A, Freeman MR, Demichelis F, De S, et al. Large extracellular vesicles carry most of the tumour DNA circulating in prostate cancer patient plasma. J Extracell Vesicles. 2018;7(1):1505403. doi:10.1080/20013078.2018.1505403.
  • Thakur BK, Zhang H, Becker A, Matei I, Huang Y, Costa-Silva B, Zheng Y, Hoshino A, Brazier H, Xiang J, et al. Double-stranded DNA in exosomes: a novel biomarker in cancer detection. Cell Res. 2014;24(6):766–769. doi:10.1038/cr.2014.44.
  • Wang W, Kong P, Ma G, Li L, Zhu J, Xia T, Xie H, Zhou W, Wang S. Characterization of the release and biological significance of cell-free DNA from breast cancer cell lines. Oncotarget. 2017;8(26):43180–43191. doi:10.18632/oncotarget.17858.
  • Zhang R, Nakahira K, Guo X, Choi AMK, Gu Z. Very short mitochondrial DNA fragments and heteroplasmy in human plasma. Sci Rep. 2016;6:1–10. doi:10.1038/srep36097.
  • Mouliere F, Chandrananda D, Piskorz AM, et al. Enhanced detection of circulating tumor DNA by fragment size analysis. Sci Transl Med. 2018;10(466):eaat4921. doi:10.1126/scitranslmed.aat4921.
  • Agostini M, Pucciarelli S, Enzo MV, Del Bianco P, Briarava M, Bedin C, Maretto I, Friso ML, Lonardi S, Mescoli C, et al. Circulating cell-free DNA: a promising marker of pathologic tumor response in rectal cancer patients receiving preoperative chemoradiotherapy. Ann Surg Oncol. 2011;18(9):2461–2468. doi:10.1245/s10434-011-1638-y.
  • Beyer C, Stearns NA, Giessl A, Distler JHW, Schett G, Pisetsky DS. The extracellular release of DNA and HMGB1 from Jurkat T cells during in vitro necrotic cell death. Innate Immun. 2012;18(5):727–737. doi:10.1177/1753425912437981.
  • Beyer C, Pisetsky DS. Modeling nuclear molecule release during in vitro cell death. Autoimmunity. 2013;46(5):298–301. doi:10.3109/08916934.2012.750297.
  • Cheng C, Omura-Minamisawa M, Kang Y, Hara T, Koike I, Inoue T. Quantification of circulating cell-free DNA in the plasma of cancer patients during radiation therapy. Cancer Sci. 2009;100(2):303–309. doi:10.1111/j.1349-7006.2008.01021.x.
  • Mouliere F, Piskorz AM, Chandrananda D, et al. Selecting short DNA fragments in plasma improves detection of circulating tumour DNA. bioRxiv. 2017;134437. doi:10.1101/134437.
  • Underhill HR, Kitzman JO, Hellwig S, Welker NC, Daza R, Baker DN, Gligorich KM, Rostomily RC, Bronner MP, Shendure J, et al. Fragment length of circulating tumor DNA. PLoS Genet. 2016;12(7):1–24. doi:10.1371/journal.pgen.1006162.
  • Cherepanova AV, Tamkovich SN, Bryzgunova OE, Vlassov VV, Laktionov PP. Deoxyribonuclease activity and circulating DNA concentration in blood plasma of patients with prostate tumors. Ann N Y Acad Sci. 2008;1137:218–221. doi:10.1196/annals.1448.016.
  • Chen H, Sun L, Zheng H, Zhang Q, Jin X. Total serum DNA and DNA integrity: diagnostic value in patients with hepatitis B virus-related hepatocellular carcinoma. Pathology. 2012;44(4):318–324. doi:10.1097/PAT.0b013e328353a24c.
  • Gang F, Guorong L, An Z, Anne GP, Christian G, Jacques T. Prediction of clear cell renal cell carcinoma by integrity of cell-free DNA in serum. Urology. 2010;75(2):262–265. doi:10.1016/j.urology.2009.06.048.
  • Bronkhorst AJ, Wentzel JF, Aucamp J, van Dyk E, Du Plessis L, Pretorius PJ. Characterization of the cell-free DNA released by cultured cancer cells. Biochim Biophys Acta - Mol Cell Res. 2016;1863(1):157–165. doi:10.1016/j.bbamcr.2015.10.022.
  • Roy S, Coldren C, Karunamurthy A, Kip NS, Klee EW, Lincoln SE, Leon A, Pullambhatla M, Temple-Smolkin RL, Voelkerding KV, et al. Standards and guidelines for validating next-generation sequencing bioinformatics pipelines: a joint recommendation of the Association for Molecular Pathology and the College of American Pathologists. J Mol Diagnostics. 2018;20(1):4–27. doi:10.1016/j.jmoldx.2017.11.003.
  • Miao EA, Rajan JV, Aderem A. Caspase-1-induced pyroptotic cell death. Immunol Rev. 2011;243(1):206–214. doi:10.1111/j.1600-065X.2011.01044.x.
  • Kemp MG, Reardon JT, Lindsey-Boltz LA, Sancar A. Mechanism of release and fate of excised oligonucleotides during nucleotide excision repair. J Biol Chem. 2012;287(27):22889–22899. doi:10.1074/jbc.M112.374447.
  • Peters DL, Pretorius PJ. Origin, translocation and destination of extracellular occurring DNA - a new paradigm in genetic behaviour. Clin Chim Acta. 2011;412(11–12):806–811. doi:10.1016/j.cca.2011.01.026.
  • Moras M, Lefevre SD, Ostuni MA. From erythroblasts to mature red blood cells: organelle clearance in mammals. Front Physiol. 2017;8(DEC):1–9. doi:10.3389/fphys.2017.01076.
  • Yipp BG, Petri B, Salina D, et al. Dynamic NETosis is carried out by live neutrophils in human and mouse bacterial abscesses and during severe gram-positive infection. Nat Med. 2012;18(9):1386–1393. doi:10.1038/nm.2847.
  • Sansone P, Savini C, Kurelac I, et al. Packaging and transfer of mitochondrial DNA via exosomes regulate escape from dormancy in hormonal therapy-resistant breast cancer. Proc Natl Acad Sci. 2017;11:E9066–E9075. doi:10.1073/pnas.1704862114.
  • Ingelsson B, Söderberg D, Strid T, Söderberg A, Bergh A-C, Loitto V, Lotfi K, Segelmark M, Spyrou G, Rosén A. Lymphocytes eject interferogenic mitochondrial DNA webs in response to CpG and non-CpG oligodeoxynucleotides of class C. Proc Natl Acad Sci. 2018;115(3):E478–E487. doi:10.1073/pnas.1711950115.
  • Marsman G, Zeerleder S, Luken BM. Extracellular histones, cell-free DNA, or nucleosomes: differences in immunostimulation. Cell Death Dis. 2016;7(12):e2518. doi:10.1038/cddis.2016.410.
  • Demers M, Wagner DD. NETosis: a new factor in tumor progression and cancer- associated thrombosis. Semin Thromb Hemost. 2014;40(3):277–283. doi:10.1055/s-0034-1370765.NETosis.
  • Yang H, Biermann MH, Brauner JM, Liu Y, Zhao Y, Herrmann M. New insights into neutrophil extracellular traps: mechanisms of formation and role in inflammation. Front Immunol. 2016;7(AUG):1–8. doi:10.3389/fimmu.2016.00302.
  • Kazzaz NM, Sule G, Knight JS, Knight JS. Intercellular interactions as regulators of NETosis. 2016;7(November):1–11. doi:10.3389/fimmu.2016.00453.
  • Kappelmayer J, Jr BN. The interaction of selectins and PSGL-1 as a key component in thrombus formation and cancer progression. 2017;2017:6138145.
  • Chiu RWK, Chan LYS, Lam NYL, et al. Quantitative analysis of circulating mitochondrial DNA in plasma. Clin Chem. 2003;49(5):719–726. doi:10.1373/49.5.719.
  • Wang H, Li T, Chen S, Gu Y, Ye S. Neutrophil extracellular trap mitochondrial DNA and its autoantibody in systemic lupus erythematosus and a proof-of-concept trial of metformin. Arthritis Rheumatol. 2015;67(12):3190–3200. doi:10.1002/art.39296.
  • Itagaki K, Kaczmarek E, Lee YT, et al. Mitochondrial DNA released by trauma induces neutrophil extracellular traps. PLoS One. 2015;10(3):1–10. doi:10.1371/journal.pone.0120549.
  • Leung F, Kulasingam V, Diamandis EP, et al. Circulating tumor DNA as a cancer biomarker: fact or fiction? Clin Chem. 2016;62(8):1054–1060. doi:10.1373/clinchem.2016.260331.
  • Celec P, Vlková B, Lauková L, Bábíčková J, Boor P. Cell-free DNA: the role in pathophysiology and as a biomarker in kidney diseases. Expert Rev Mol Med. 2018;20:1–14. doi:10.1017/erm.2017.12.
  • Thierry AR, Mouliere F, Gongora C, et al. Origin and quantification of circulating DNA in mice with human colorectal cancer xenografts. Nucleic Acids Res. 2010;38(18):6159–6175. doi:10.1093/nar/gkq421.
  • García Moreira V, De La Cera Martínez T, Gago González E, Prieto García B, Alvarez Menéndez FV. Increase in and clearance of cell-free plasma DNA in hemodialysis quantified by real-time PCR. Clin Chem Lab Med. 2006;44(12):1410–1415. doi:10.1515/CCLM.2006.252.
  • Gauthier VJ, Tyler LN, Mannik M. Blood clearance kinetics and liver uptake of mononucleosomes in mice. J Immunol. 1996;156(3):1151–1156.
  • Yu SCY, Lee SWY, Jiang P, et al. High-resolution profiling of fetal DNA clearance from maternal plasma by massively parallel sequencing. Clin Chem. 2013;59(8):1228–1237. doi:10.1373/clinchem.2013.203679.
  • Diehl F, Schmidt K, Choti MA, et al. Circulating mutant DNA to assess tumor dynamics. Nat Med. 2008;14(9):985–990. doi:10.1038/nm.1789.
  • Stephan F, Marsman G, Bakker LM, et al. Cooperation of factor vii-activating protease and serum DNase I in the release of nucleosomes from necrotic cells. Arthritis Rheumatol. 2014;66(3):686–693. doi:10.1002/art.38265.
  • Martin M, Leffler J, Smolag KI, et al. Factor H uptake regulates intracellular C3 activation during apoptosis and decreases the inflammatory potential of nucleosomes. Cell Death Differ. 2016;23(5):903–911. doi:10.1038/cdd.2015.164.
  • Tamkovich SN, Cherepanova A V., Kolesnikova E V., et al. Circulating DNA and DNase activity in human blood. Ann N Y Acad Sci. 2006;1075:191–196. doi:10.1196/annals.1368.026.
  • Butler TM, Spellman PT, Gray J. Circulating-tumor DNA as an early detection and diagnostic tool. Curr Opin Genet Dev. 2017;42:14–21. doi:10.1016/j.gde.2016.12.003.
  • Du Clos TW, Volzer MA, Hahn FF, Xiao R, Mold C, Searles RP. Chromatin clearance in C57B1/10 mice: interaction with heparan sulphate proteoglycans and receptors on Kupffer cells. Clin Exp Immunol. 1999;117(2):403–411. doi:10.1046/j.1365-2249.1999.00976.x.
  • Koizumi T. Tissue distribution of deoxyribonuclease I (DNase I) activity level in mice and its sexual dimorphism. Exp Anim. 1995;44(3):181–185. doi:10.1538/expanim.44.181.
  • Abrams ST, Zhang N, Manson J, et al. Circulating histones are mediators of trauma-associated lung injury. Am J Respir Crit Care Med. 2013;187(2):160–169. doi:10.1164/rccm.201206-1037OC.
  • Xu J, Zhang X, Pelayo R, et al. Extracellular histones are major mediators of death in sepsis. Nat Med. 2009;15(11):1318–1321. doi:10.1038/nm.2053.
  • Zhang Q, Raoof M, Chen Y, Sumi Y, Sursal T, Junger W, Brohi K, Itagaki K, Hauser CJ. Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature. 2010;464(7285):104–107. doi:10.1038/nature08780.
  • Paunel-Görgülü A, Wacker M, El Aita M, Hassan S, Schlachtenberger G, Deppe A, Choi Y-H, Kuhn E, Mehler TO, Wahlers T. cfDNA correlates with endothelial damage after cardiac surgery with prolonged cardiopulmonary bypass and amplifies NETosis in an intracellular TLR9-independent manner. Sci Rep. 2017;7(1):17421. doi:10.1038/s41598-017-17561-1.
  • Bhagirath VC, Dwivedi DJ, Liaw PC. Comparison of the proinflammatory and procoagulant properties of nuclear, mitochondrial, and bacterial DNA. Shock. 2015;44(3):265–271. doi:10.1097/SHK.0000000000000397.
  • Xu MM, Pu Y, Han D, Shi Y, Cao X, Liang H, Chen X, Li X-D, Deng L, Chen ZJ, et al. Dendritic cells but not macrophages sense tumor mitochondrial DNA for cross-priming through signal regulatory protein α signaling. Immunity. 2017;47(2):363–373.e5. doi:10.1016/j.immuni.2017.07.016.
  • Nishimoto S, Fukuda D, Higashikuni Y, et al. Obesity-induced DNA released from adipocytes stimulates chronic adipose tissue inflammation and insulin resistance. 2016;6(March):1–11.
  • Corrêa LH, Corrêa R, Farinasso CM, Pimentel L, Dourado DSA, Magalhães KG. Adipocytes and macrophages interplay in the orchestration of tumor microenvironment: new implications in cancer progression. 2017;8(September):1–12. doi:10.3389/fimmu.2017.01129.
  • Dunphy G, Flannery SM, Almine JF, Connolly DJ, Paulus C, Jønsson KL, Jakobsen MR, Nevels MM, Bowie AG, Unterholzner L. Non-canonical activation of the DNA sensing adaptor STING by ATM and IFI16 mediates NF-κB signaling after nuclear DNA damage. Mol Cell. 2018;71(5):745–760.e5. doi:10.1016/j.molcel.2018.07.034.
  • Parkes EE, Walker SM, Taggart LE, et al. Activation of STING-dependent innate immune signaling by s-phase-specific DNA damage in breast cancer. J Natl Cancer Inst. 2017;109:1. doi:10.1093/jnci/djw199.
  • Ahn J, Xia T, Konno H, Konno K, Ruiz P, Barber GN. Inflammation-driven carcinogenesis is mediated through STING. Nat Commun. 2014;5:1–9. doi:10.1038/ncomms6166.
  • Härtlova A, Erttmann SF, Raffi FAM, Schmalz AM, Resch U, Anugula S, Lienenklaus S, Nilsson LM, Kröger A, Nilsson JA, et al. DNA damage primes the type I interferon system via the cytosolic DNA sensor STING to promote anti-microbial innate immunity. Immunity. 2015;42(2):332–343. doi:10.1016/j.immuni.2015.01.012.
  • Chen G, Huang AC, Zhang W, Zhang G, Wu M, Xu W, Yu Z, Yang J, Wang B, Sun H, et al. Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response. Nature. 2018;560:382–386. doi:10.1038/s41586-018-0392-8.
  • Theodoraki M-N, Yerneni S, Hoffmann TK, Gooding WE, Whiteside TL. Clinical significance of PD-L1+ exosomes in plasma of head and neck cancer patients. Clin Cancer Res. 2017;24(4):clincanres.2664.2017. doi:10.1158/1078-0432.CCR-17-2664.
  • Yang Y, Li CW, Chan LC, et al. Exosomal PD-L1 harbors active defense function to suppress T cell killing of breast cancer cells and promote tumor growth. Cell Res. 2018;(January):1–3. doi:10.1038/s41422-018-0060-4.
  • Cabel L, Riva F, Servois V, Livartowski A, Daniel C, Rampanou A, Lantz O, Romano E, Milder M, Buecher B, et al. Circulating tumor DNA changes for early monitoring of anti-PD1 immunotherapy: a proof-of-concept study. Ann Oncol. 2017;28:1996–2001. doi:10.1093/annonc/mdx212.
  • Kim ST, Cristescu R, Bass AJ, Kim K-M, Odegaard JI, Kim K, Liu XQ, Sher X, Jung H, Lee M, et al. Comprehensive molecular characterization of clinical responses to PD-1 inhibition in metastatic gastric cancer. Nat Med. 2018;24(9):1449–1458. doi:10.1038/s41591-018-0101-z.
  • Raja R, Kuziora M, Brohawn PZ, Higgs BW, Gupta A, Dennis PA, Ranade K. Early reduction in ctDNA predicts survival in patients with lung and bladder cancer treated with durvalumab. Clin Cancer Res. 2018;24(24):6212–6222. doi:10.1158/1078-0432.CCR-18-0386.
  • Takahashi A, Okada R, Nagao K, et al. Exosomes maintain cellular homeostasis by excreting harmful DNA from cells. Nat Commun. 2017;8(May):1–14. doi:10.1038/ncomms15287.
  • Trejo-Becerril C, Pérez-Cárdenas E, Taja-Chayeb L, Anker P, Herrera-Goepfert R, Medina-Velázquez LA, Hidalgo-Miranda A, Pérez-Montiel D, Chávez-Blanco A, Cruz-Velázquez J, et al. Cancer progression mediated by horizontal gene transfer in an in vivo model. PLoS One. 2012;7(12):1–12. doi:10.1371/journal.pone.0052754.
  • García-Olmo D, García-Olmo DC, Ontañón J, Martinez E, Vallejo M. Tumor DNA circulating in the plasma might play a role in metastasis. The hypothesis of the genometastasis. Histol Histopathol. 1999;14(4):1159–1164. doi:10.14670/HH-14.1159.
  • Mittra I, Khare NK, Raghuram GV, Chaubal R, Khambatti F, Gupta D, Gaikwad A, Prasannan P, Singh A, Iyer A, et al. Circulating nucleic acids damage DNA of healthy cells by integrating into their genomes. J Biosci. 2015;40(1):91–111. doi:10.1007/s12038-015-9508-6.
  • García-Casas A, García-Olmo DC, García-Olmo D. Further the liquid biopsy: gathering pieces of the puzzle of genometastasis theory. World J Clin Oncol. 2017;8(5):378–388. doi:10.5306/wjco.v8.i5.378.
  • Furi I, Kalmár A, Wichmann B, Spisák S, Schöller A, Barták B, Tulassay Z, Molnár B, Castresana JS. Cell free DNA of tumor origin induces a “metastatic” expression profile in HT-29 cancer cell line. PLoS One. 2015;10(7):1–16. doi:10.1371/journal.pone.0131699.
  • Lee TH, Chennakrishnaiah S, Meehan B, et al. Barriers to horizontal cell transformation by extracellular vesicles containing oncogenic H-ras. Oncotarget. 2016;7(32):8–11. doi:10.18632/oncotarget.10627.
  • Cai J, Han Y, Ren H, Chen C, He D, Zhou L, Eisner GM, Asico LD, Jose PA, Zeng C. Extracellular vesicle-mediated transfer of donor genomic DNA to recipient cells is a novel mechanism for genetic influence between cells. J Mol Cell Biol. 2013;5(4):227–238. doi:10.1093/jmcb/mjt011.
  • Islam MN, Das SR, Emin MT, Wei M, Sun L, Westphalen K, Rowlands DJ, Quadri SK, Bhattacharya S, Bhattacharya J. Mitochondrial transfer from bone-marrow-derived stromal cells to pulmonary alveoli protects against acute lung injury. Nat Med. 2012;18(5):759–765. doi:10.1038/nm.2736.
  • Liu K, Ji K, Guo L, Wu W, Lu H, Shan P, Yan C. Mesenchymal stem cells rescue injured endothelial cells in an in vitro ischemia-reperfusion model via tunneling nanotube like structure-mediated mitochondrial transfer. Microvasc Res. 2014;92:10–18. doi:10.1016/j.mvr.2014.01.008.
  • Guescini M, Genedani S, Stocchi V, Agnati LF. Astrocytes and glioblastoma cells release exosomes carrying mtDNA. J Neural Transm. 2010;117(1):1–4. doi:10.1007/s00702-009-0288-8.
  • Ling S, Martinod K, Gallant M, Cabral JE, Wang Y. Priming of neutrophils toward NETosis promotes tumor growth. 2016;5(5):1–9. doi:10.1080/2162402X.2015.1134073.
  • Swystun LL, Mukherjee S, Liaw PC. Breast cancer chemotherapy induces the release of cell-free DNA, a novel procoagulant stimulus. J Thromb Haemost. 2011;9(11):2313–2321. doi:10.1111/j.1538-7836.2011.04465.x.
  • Olsson A, Cedervall J. NETosis in cancer – platelet–neutrophil crosstalk promotes tumor-associated pathology. 2016;7(September):2–9. doi:10.3389/fimmu.2016.00373.
  • Tohme S, Yazdani HO, Al-Khafaji AB, Chidi AP, Loughran P, Mowen K, Wang Y, Simmons RL, Huang H, Tsung A. Neutrophil extracellular traps promote the development and progression of liver metastases after surgical stress. Cancer Res. 2016;76(6):1367–1380. doi:10.1158/0008-5472.CAN-15-1591.
  • Park J, Wysocki RW, Amoozgar Z, et al. Cancer cells induce metastasis-supporting neutrophil extracellular DNA traps. Cancer. 2016;8(361):361ra138.
  • Erpenbeck L, Schön MP. Neutrophil extracellular traps: protagonists of cancer progression? Oncogene. 2017;36(18):2483–2490. doi:10.1038/onc.2016.406.
  • Albrengues J, Shields MA, Ng D, Park CG, Ambrico A, Poindexter ME, Upadhyay P, Uyeminami DL, Pommier A, Küttner V, et al. Neutrophil extracellular traps produced during inflammation awaken dormant cancer cells in mice. Science (80-). 2018;361:6409. doi:10.1126/science.aao4227.
  • Mouchemore KA, Anderson RL, Hamilton JA. Neutrophils, G-CSF and their contribution to breast cancer metastasis. FEBS J. 2017;285:665–679. doi:10.1111/febs.14206.
  • Cedervall J, Olsson A. NETosis in cancer. Oncoscience. 2015;2(11):11–12.
  • Etulain J, Martinod K, Wong SL, Cifuni SM, Schattner M, Wagner DD. Brief Report P-selectin promotes neutrophil extracellular trap formation in mice. Blood. 2018;126(14):242–247. doi:10.1182/blood-2015-01-624023.The.
  • Pfeiler S, Stark K, Massberg S, Engelmann B. Propagation of thrombosis by neutrophils and extracellular nucleosome networks. Haematologica. 2017;102(2):206–213. doi:10.3324/haematol.2016.142471.
  • Jablonska J, Lang S, Sionov RV, et al. The regulation of pre-metastatic niche formation by neutrophils. Oncotarget. 2017;8(67):112132–112144. doi:10.18632/oncotarget.22792.
  • Corriden R, Hollands A, Olson J, Derieux J, Lopez J, Chang JT, Gonzalez DJ, Nizet V. Tamoxifen augments the innate immune function of neutrophils through modulation of intracellular ceramide. Nat Commun. 2015;6:8369. doi:10.1038/ncomms9369.
  • Flores R, Döhrmann S, Schaal C, Hakkim A, Nizet V, Corriden R. The selective estrogen receptor modulator raloxifene inhibits neutrophil extracellular trap formation. Front Immunol. 2016;7:556. doi:10.3389/fimmu.2016.00566.