Origins, structures, and functions of circulating DNA in oncology

Cancer and Metastasis Reviews

Volumn 35, Issue 3, 2016, Pages 347-376

  Thierry, A R ^a   El Messaoudi, S ^a   Gahan, P B ^a   Anker, P ^b   Stroun, M ^b  

^a INSTITUT DE RECHERCHE EN CANCÉROLOGIE DE MONTPELLIER   (France)

^b NONE   (Switzerland)

Author keywords

Cancer; Cell free circulating DNA; Functions; Origins; Structures

Indexed keywords

CELL FREE CIRCULATING DNA; DNA; GENOMIC DNA; LIPOPROTEIN; MITOCHONDRIAL DNA; NUCLEIC ACID; UNCLASSIFIED DRUG; CIRCULAR DNA; MACROMOLECULE; TUMOR MARKER;

APOPTOSIS; ARTICLE; B LYMPHOCYTE; CANCER PATIENT; CARDIOVASCULAR SYSTEM; CELL DIFFERENTIATION; CELL SURFACE; CIRCULATING TUMOR CELL; DNA STRUCTURE; EOSINOPHIL; FOLLOW UP; HUMAN; IMMUNITY; MITOCHONDRION; NEOPLASM; NEUTROPHIL; NUCLEOSOME; ONCOLOGY; PERSONALIZED MEDICINE; PHAGOCYTOSIS; PRIORITY JOURNAL; SYSTEMIC LUPUS ERYTHEMATOSUS; T LYMPHOCYTE; TUMOR CELL; TUMOR GROWTH; ANIMAL; BLOOD; CHEMISTRY; DISEASE MODEL; DNA FRAGMENTATION; EXOSOME; EXTRACELLULAR TRAP; GENETICS; MACROMOLECULE; MEMBRANE MICROPARTICLE; METABOLISM; MORTALITY; MUTATION; NEOPLASMS; PROGNOSIS; TUMOR EMBOLISM; TUMOR VOLUME;

ANIMALS; BIOMARKERS, TUMOR; CELL-DERIVED MICROPARTICLES; DISEASE MODELS, ANIMAL; DNA FRAGMENTATION; DNA, CIRCULAR; DNA, MITOCHONDRIAL; DNA, NEOPLASM; EXOSOMES; EXTRACELLULAR TRAPS; EXTRACELLULAR VESICLES; HUMANS; LIPOPROTEINS; MACROMOLECULAR SUBSTANCES; MUTATION; NEOPLASMS; NEOPLASTIC CELLS, CIRCULATING; PROGNOSIS; TUMOR BURDEN;

EID: 84978036286     PISSN: 01677659     EISSN: 15737233     Source Type: Journal    
DOI: 10.1007/s10555-016-9629-x     Document Type: Article

References (238)

1. Fleischhacker M, Schmidt B (2007) Circulating nucleic acids (CNAs) and cancer--a survey. Biochimica et Biophysica Acta 1775(1):181–232. doi:10.1016/j.bbcan.2006.10.001
2. Gahan PB, Swaminathan R (2008) Circulating nucleic acids in plasma and serum. Recent developments. Annals of the New York Academy of Sciences 1137:1–6. doi:10.1196/annals.1448.050
3. Miescher F (1871) Ueber die chemische Zusammensetzung der Eiterzellen. Medicinisch-chemische Untersuchungen 4:441–460
4. Levene PA, Haller HL (1929) On the configurational relationship of 3-Chlorobutyric and 3-Hydroxybutyric acids. Science (New York, NY) 69(1776):47. doi:10.1126/science.69.1776.47
5. Beadle GW, Tatum EL (1941) Genetic Control of Biochemical Reactions in Neurospora. Proceedings of the National Academy of Sciences of the United States of America 27(11):499–506
6. McClintock B (1941) The Stability of Broken Ends of Chromosomes in Zea Mays. Genetics 26(2):234–282
7. Avery OT, Macleod CM, McCarty M (1944) Studies on the chemical nature of the substance inducing transformation of pneumococcal types: induction of transformation by a Desoxyribonucleic acid fraction isolated from Pneumococcus TYPE III. The Journal of Experimental Medicine 79(2):137–158
8. Mandel P, Métais P (1948) Les acides nucléiques du plasma sanguin chez l’Homme. Comptes Rendus des Seances de la Societe de Biologie et de ses Filiales 142:241–243
9. Chayen J, Norris KP (1953) Cytoplasmic localization of nucleic acids in plant cells. Nature 171(4350):472–473
10. Swift H (1950) The constancy of desoxyribose nucleic acid in plant nuclei. Proceedings of the National Academy of Sciences of the United States of America 36(11):643–654
11. Chargaff E (1950) Chemical specificity of nucleic acids and mechanism of their enzymatic degradation. Experientia 6(6):201–209
12. Watson JD, Crick FH (1953) The structure of DNA. Cold Spring Harbor Symposia on Quantitative Biology 18:123–131
13. Wilkins MHF, Stokes AR, Wilson HR (1953) Molecular Structure of Nucleic Acids: Molecular Structure of Deoxypentose Nucleic Acids. Nature 171(4356):738–740. doi:10.1038/171738a0
14. Sinsheimer RL (1957) First steps toward a genetic chemistry. Science (New York, NY) 125(3258):1123–1128
15. Gartler SM (1959) Cellular uptake of deoxyribonucleic acid by human tissue culture cells. Nature 184(Suppl 19):1505–1506
16. Stroun M (1962) Modifications des caractères à la suite de greffes intervariétales chez le Solanum melongena. Comptes Rendues á l’Academie de Science Paris 255:361–363
17. Gahan PB, Chayen J, Silcox AA (1962) Cytoplasmic localization of deoxyribonucleic acid in Allium cepa. Nature 195:1115–1116
18. Gahan PB, Chayen J (1965) Cytoplasmic deoxyribonucleic acid. International Review of Cytology 18:223–247
19. Stroun M, Anker P (1972) Nucleic acids spontaneously released by living frog auricles. The Biochemical Journal 128(3):100P–101P
20. Stroun M, Anker P, Maurice P, Gahan PB (1977) Circulating nucleic acids in higher organisms. International Review of Cytology 51:1–48
21. Leon SA, Shapiro B, Sklaroff DM, Yaros MJ (1977) Free DNA in the serum of cancer patients and the effect of therapy. Cancer Research 37(3):646–650
22. Stroun M, Anker P, Maurice P, Lyautey J, Lederrey C, Beljanski M (1989) Neoplastic characteristics of the DNA found in the plasma of cancer patients. Oncology 46(5):318–322
23. Vasioukhin V, Anker P, Maurice P, Lyautey J, Lederrey C, Stroun M (1994) Point mutations of the N-ras gene in the blood plasma DNA of patients with myelodysplastic syndrome or acute myelogenous leukaemia. British Journal of Haematology 86(4):774–779
24. Sorenson GD, Pribish DM, Valone FH, Memoli VA, Bzik DJ, Yao SL (1994) Soluble normal and mutated DNA sequences from single-copy genes in human blood. Cancer Epidemiology, Biomarkers and Prevention 3(1):67–71
25. Lo YM, Corbetta N, Chamberlain PF, Rai V, Sargent IL, Redman CW, Wainscoat JS (1997) Presence of fetal DNA in maternal plasma and serum. Lancet 350(9076):485–487. doi:10.1016/S0140-6736(97)02174-0
26. Diehl F, Li M, Dressman D, He Y, Shen D, Szabo S, Vogelstein B (2005) Detection and quantification of mutations in the plasma of patients with colorectal tumors. Proceedings of the National Academy of Sciences of the United States of America 102(45):16368–16373. doi:10.1073/pnas.0507904102
27. Tan EM, Schur PH, Carr RI, Kunkel HG (1966) Deoxybonucleic acid (DNA) and antibodies to DNA in the serum of patients with systemic lupus erythematosus. The Journal of Clinical Investigation 45(11):1732–1740. doi:10.1172/JCI105479
28. Yu SCY, Chan KCA, Zheng YWL, Jiang P, Liao GJW, Sun H, Lo YMD (2014) Size-based molecular diagnostics using plasma DNA for noninvasive prenatal testing. Proceedings of the National Academy of Sciences of the United States of America 111(23):8583–8588. doi:10.1073/pnas.1406103111
29. Mennuti MT, Chandrasekaran S, Khalek N, Dugoff L (2015) Cell-free DNA screening and sex chromosome aneuploidies. Prenatal Diagnosis 35(10):980–985. doi:10.1002/pd.4639
30. Rieneck K, Clausen FB, Dziegiel MH (2015) Noninvasive Antenatal Determination of Fetal Blood Group Using Next-Generation Sequencing. Cold Spring Harbor Perspectives in Medicine 6(1):a023093. doi:10.1101/cshperspect.a023093
31. Assou S, Aït-Ahmed O, El Messaoudi S, Thierry AR, Hamamah S (2014) Non-invasive pre-implantation genetic diagnosis of X-linked disorders. Medical Hypotheses 83(4):506–508. doi:10.1016/j.mehy.2014.08.019
32. Swarup V, Rajeswari MR (2007) Circulating (cell-free) nucleic acids--a promising, non-invasive tool for early detection of several human diseases. FEBS Letters 581(5):795–799. doi:10.1016/j.febslet.2007.01.051
33. Crowley E, Di Nicolantonio F, Loupakis F, Bardelli A (2013) Liquid biopsy: monitoring cancer-genetics in the blood. Nature Reviews. Clinical Oncology 10(8):472–484. doi:10.1038/nrclinonc.2013.110
34. Heitzer E, Ulz P, Geigl JB (2015) Circulating tumor DNA as a liquid biopsy for cancer. Clinical Chemistry 61(1):112–123. doi:10.1373/clinchem.2014.222679
35. Thierry AR (2015) Circulating DNA and cancer. AACR Education Book 2015(1):45. doi:10.1158/AACR.EDB-15-7973
36. Harbeck RJ, Bardana EJ, Kohler PF, Carr RI (1973) DNA:anti-DNA complexes: their detection in systemic lupus erythematosus sera. The Journal of Clinical Investigation 52(4):789–795. doi:10.1172/JCI107242
37. Compton LJ, Steinberg AD, Sano H (1984) Nuclear DNA degradation in lymphocytes of patients with systemic lupus erythematosus. Journal of Immunology (Baltimore, Md: 1950) 133(1):213–216
38. Koffler D, Agnello V, Winchester R, Kunkel HG (1973) The Occurrence of Single-Stranded DNA in the Serum of Patients with Systemic Lupus Erythematosus and Other Diseases. Journal of Clinical Investigation 52(1):198–204
39. Li JZ, Steinman CR (1989) Plasma DNA in systemic lupus erythematosus. Characterization of cloned base sequences. Arthritis and Rheumatism 32(6):726–733
40. Raptis L, Menard HA (1980) Quantitation and characterization of plasma DNA in normals and patients with systemic lupus erythematosus. The Journal of Clinical Investigation 66(6):1391–1399. doi:10.1172/JCI109992
41. Rumore PM, Steinman CR (1990) Endogenous circulating DNA in systemic lupus erythematosus. Occurrence as multimeric complexes bound to histone. The Journal of Clinical Investigation 86(1):69–74. doi:10.1172/JCI114716
42. Steinman CR (1975) Free DNA in serum and plasma from normal adults. Journal of Clinical Investigation 56(2):512–515
43. Tan EM (1967) An immunologic precipitin system between soluble nucleoprotein and serum antibody in systemic lupus erythematosus. The Journal of Clinical Investigation 46(5):735–745. doi:10.1172/JCI105574
44. Volkova ZI, Solov’ev GI, Folomeeva OM (1980) Isolation and characteristics of the DNA of donor and systemic lupus erythematosus patient blood plasma. Biulleten' Eksperimental'noĭ Biologii i Meditsiny 89(6):689–691
45. Emlen W, Mannik M (1984) Effect of DNA size and strandedness on the in vivo clearance and organ localization of DNA. Clinical and Experimental Immunology 56(1):185–192
46. Stroun M, Anker P, Lyautey J, Lederrey C, Maurice PA (1987) Isolation and characterization of DNA from the plasma of cancer patients. European Journal of Cancer & Clinical Oncology 23(6):707–712
47. Mouliere F, Thierry AR (2012) The importance of examining the proportion of circulating DNA originating from tumor, microenvironment and normal cells in colorectal cancer patients. Expert Opinion on Biological Therapy 12(S1):S209–S215. doi:10.1517/14712598.2012.688023
48. Rykova EY, Morozkin ES, Ponomaryova AA, Loseva EM, Zaporozhchenko IA, Cherdyntseva NV, Laktionov PP (2012) Cell-free and cell-bound circulating nucleic acid complexes: mechanisms of generation, concentration and content. Expert Opinion on Biological Therapy 12(Suppl 1):S141–153. doi:10.1517/14712598.2012.673577
49. Laktionov PP, Tamkovich SN, Rykova EY, Bryzgunova OE, Starikov AV, Kuznetsova NP, Vlassov VV (2004) Cell-surface-bound nucleic acids: Free and cell-surface-bound nucleic acids in blood of healthy donors and breast cancer patients. Annals of the New York Academy of Sciences 1022:221–227. doi:10.1196/annals.1318.034
50. Mittra I, Nair NK, Mishra PK (2012) Nucleic acids in circulation: are they harmful to the host? Journal of Biosciences 37(2):301–312
51. Gahan PB, Stroun M (2010) The virtosome-a novel cytosolic informative entity and intercellular messenger. Cell Biochemistry and Function 28(7):529–538. doi:10.1002/cbf.1690
52. Rogers JC, Boldt D, Kornfeld S, Skinner A, Valeri CR (1972) Excretion of deoxyribonucleic acid by lymphocytes stimulated with phytohemagglutinin or antigen. Proceedings of the National Academy of Sciences of the United States of America 69(7):1685–1689
53. Anker P, Stroun M (1972) Bacterial ribonucleic acid synthesis in frog organs after intraperitoneal injection of bacteria. Biochemical Journal 128(3):101P
54. Anker P, Stroun M (1972) Bacterial ribonucleic acid in the frog brain after a bacterial peritoneal infection. Science (New York, NY) 178(4061):621–623
55. Anker P, Mulcahy H, Chen XQ, Stroun M (1999) Detection of circulating tumour DNA in the blood (plasma/serum) of cancer patients. Cancer Metastasis Reviews 18(1):65–73
56. Stroun M, Anker P (1971) Bacterial nucleic acid synthesis in plants following bacterial contact. Molecular and General Genetics MGG 113(1):92–98
57. Stroun M, Anker P (1973) Transcription of Spontaneously Released Bacterial Deoxyribonucleic Acid in Frog Auricles. Journal of Bacteriology 114(1):114–120
58. Stroun M, Charles P, Anker P, Pelc SR (1967) Metabolic DNA in heart and skeletal muscle and in the intestine of mice. Nature 216(5116):716–717
59. Stroun M, Anker P, Gahan P, Rossier A, Greppin H (1971) Agrobacterium tumefaciens ribonucleic acid synthesis in tomato cells and crown gall induction. Journal of Bacteriology 106(2):634–639
60. Anker P, Stroun M, Maurice PA (1975) Spontaneous release of DNA by human blood lymphocytes as shown in an in vitro system. Cancer Research 35(9):2375–2382
61. Stroun M, Lyautey J, Lederrey C, Olson-Sand A, Anker P (2001) About the possible origin and mechanism of circulating DNA: Apoptosis and active DNA release. Clinica Chimica Acta 313(1–2):139–142. doi:10.1016/S0009-8981(01)00665-9
62. Gahan PB, Anker P, Stroun M (2008) Metabolic DNA as the origin of spontaneously released DNA? Annals of the New York Academy of Sciences 1137:7–17. doi:10.1196/annals.1448.046
63. Abolhassani M, Tillotson J, Chiao J (1994) Characterization of the release of DNA by a human leukemia-cell line HL-60. International Journal of Oncology 4(2):417–421
64. Meyer JS (1981) Growth and cell kinetic measurements in human tumors. Pathology Annual 16(Pt 2):53–81
65. Ota DM, Drewinko B (1985) Growth kinetics of human colorectal carcinoma. Cancer Research 45(5):2128–2131
66. Lo CF (2007) Stochastic Gompertz model of tumour cell growth. Journal of Theoretical Biology 248(2):317–321. doi:10.1016/j.jtbi.2007.04.024
67. Bettegowda C, Sausen M, Leary RJ, Kinde I, Wang Y, Agrawal N, Diaz LA (2014) Detection of Circulating Tumor DNA in Early- and Late-Stage Human Malignancies. Science Translational Medicine 6(224):224ra24–224ra24. doi:10.1126/scitranslmed.3007094
68. Mouliere F, El Messaoudi S, Gongora C, Guedj A-S, Robert B, Del Rio M, Thierry AR (2013) Circulating Cell-Free DNA from Colorectal Cancer Patients May Reveal High KRAS or BRAF Mutation Load. Translational Oncology 6(3):319–328
69. Mouliere F, El Messaoudi S, Pang D, Dritschilo A, Thierry AR (2014) Multi-marker analysis of circulating cell-free DNA toward personalized medicine for colorectal cancer. Molecular Oncology 8(5):927–941. doi:10.1016/j.molonc.2014.02.005
70. Thierry AR, Mouliere F, El Messaoudi S, Mollevi C, Lopez-Crapez E, Rolet F, Ychou M (2014) Clinical validation of the detection of KRAS and BRAF mutations from circulating tumor DNA. Nature Medicine 20(4):430–435. doi:10.1038/nm.3511
71. Esposito A, Bardelli A, Criscitiello C, Colombo N, Gelao L, Fumagalli L, Curigliano G (2014) Monitoring tumor-derived cell-free DNA in patients with solid tumors: Clinical perspectives and research opportunities. Cancer Treatment Reviews 40(5):648–655. doi:10.1016/j.ctrv.2013.10.003
72. Mouliere F, Robert B, Arnau Peyrotte E, Del Rio M, Ychou M, Molina F, Thierry AR (2011) High fragmentation characterizes tumour-derived circulating DNA. PloS One 6(9):e23418. doi:10.1371/journal.pone.0023418
73. Thierry AR, Mouliere F, Gongora C, Ollier J, Robert B, Ychou M, Molina F (2010) Origin and quantification of circulating DNA in mice with human colorectal cancer xenografts. Nucleic Acids Research 38(18):6159–6175. doi:10.1093/nar/gkq421
74. El Messaoudi S, Mouliere F, Du Manoir S, Bascoul-Mollevi C, Gillet B, Nouaille M, Thierry AR (2016) Circulating DNA as a strong multi-marker prognostic tool for metastatic colorectal cancer patient management care. Clinical Cancer Research. doi:10.1158/1078-0432.CCR-15-0297
75. Murtaza M, Dawson S-J, Tsui DWY, Gale D, Forshew T, Piskorz AM, Rosenfeld N (2013) Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA. Nature 497(7447):108–112. doi:10.1038/nature12065
76. West NP, Dattani M, McShane P, Hutchins G, Grabsch J, Mueller W, Grabsch H (2010) The proportion of tumour cells is an independent predictor for survival in colorectal cancer patients. British Journal of Cancer 102(10):1519–1523. doi:10.1038/sj.bjc.6605674
77. Spindler K-LG, Pallisgaard N, Vogelius I, Jakobsen A (2012) Quantitative cell-free DNA, KRAS, and BRAF mutations in plasma from patients with metastatic colorectal cancer during treatment with cetuximab and irinotecan. Clinical Cancer Research 18(4):1177–1185. doi:10.1158/1078-0432.CCR-11-0564
78. Boone BA, Orlichenko L, Schapiro NE, Loughran P, Gianfrate GC, Ellis JT, Zeh HJ (2015) The receptor for advanced glycation end products (RAGE) enhances autophagy and neutrophil extracellular traps in pancreatic cancer. Cancer Gene Therapy 22(6):326–334. doi:10.1038/cgt.2015.21
79. Cortese R, Almendros I, Wang Y, Gozal D (2014) Tumor circulating DNA profiling in xenografted mice exposed to intermittent hypoxia. Oncotarget 6(1):556–569
80. Sato K, Tsuchihara K, Fujii S, Sugiyama M, Goya T, Atomi Y, Esumi H (2007) Autophagy is activated in colorectal cancer cells and contributes to the tolerance to nutrient deprivation. Cancer Research 67(20):9677–9684. doi:10.1158/0008-5472.CAN-07-1462
81. Ho AS, Huang X, Cao H, Christman-Skieller C, Bennewith K, Le Q-T, Koong AC (2010) Circulating miR-210 as a Novel Hypoxia Marker in Pancreatic Cancer. Translational Oncology 3(2):109–113
82. Yu M (2012) Circulating cell-free mitochondrial DNA as a novel cancer biomarker: opportunities and challenges. Mitochondrial DNA 23(5):329–332. doi:10.3109/19401736.2012.696625
83. Ellinger J, Müller DC, Müller SC, Hauser S, Heukamp LC, von Ruecker A, Walgenbach-Brunagel G (2012) Circulating mitochondrial DNA in serum: a universal diagnostic biomarker for patients with urological malignancies. Urologic Oncology 30(4):509–515. doi:10.1016/j.urolonc.2010.03.004
84. Kohler C, Radpour R, Barekati Z, Asadollahi R, Bitzer J, Wight E, Zhong XY (2009) Levels of plasma circulating cell free nuclear and mitochondrial DNA as potential biomarkers for breast tumors. Molecular Cancer 8:105. doi:10.1186/1476-4598-8-105
85. Budnik LT, Kloth S, Baur X, Preisser AM, Schwarzenbach H (2013) Circulating mitochondrial DNA as biomarker linking environmental chemical exposure to early preclinical lesions elevation of mtDNA in human serum after exposure to carcinogenic halo-alkane-based pesticides. PloS One 8(5):e64413. doi:10.1371/journal.pone.0064413
86. Ding W-X, Yin X-M (2012) Mitophagy: mechanisms, pathophysiological roles, and analysis. Biological Chemistry 393(7):547–564. doi:10.1515/hsz-2012-0119
87. Chiu RWK, Chan LYS, Lam NYL, Tsui NBY, Ng EKO, Rainer TH, Lo YMD (2003) Quantitative analysis of circulating mitochondrial DNA in plasma. Clinical Chemistry 49(5):719–726
88. Malik AN, Parsade CK, Ajaz S, Crosby-Nwaobi R, Gnudi L, Czajka A, Sivaprasad S (2015) Altered circulating mitochondrial DNA and increased inflammation in patients with diabetic retinopathy. Diabetes Research and Clinical Practice 110(3):257–265. doi:10.1016/j.diabres.2015.10.006
89. Liu J, Cai X, Xie L, Tang Y, Cheng J, Wang J, Gong J (2015) Circulating Cell Free Mitochondrial DNA is a Biomarker in the Development of Coronary Heart Disease in the Patients with Type 2 Diabetes. Clinical Laboratory 61(7):661–667
90. Sudakov NP, Popkova TP, Katyshev AI, Goldberg OA, Nikiforov SB, Pushkarev BG, Konstantinov YM (2015) Level of Blood Cell-Free Circulating Mitochondrial DNA as a Novel Biomarker of Acute Myocardial Ischemia. Biochemistry. Biokhimiia 80(10):1387–1392. doi:10.1134/S000629791510020X
91. Surmiak MP, Hubalewska-Mazgaj M, Wawrzycka-Adamczyk K, Szczeklik W, Musiał J, Sanak M (2015) Circulating mitochondrial DNA in serum of patients with granulomatosis with polyangiitis. Clinical and Experimental Immunology 181(1):150–155. doi:10.1111/cei.12628
92. Zhang Q, Itagaki K, Hauser CJ (2010) Mitochondrial DNA is released by shock and activates neutrophils via p38 map kinase. Shock (Augusta, Ga) 34(1):55–59. doi:10.1097/SHK.0b013e3181cd8c08
93. Nasi M, Cristani A, Pinti M, Lamberti I, Gibellini L, De Biasi S, Cossarizza A (2016) Decreased Circulating mtDNA Levels in Professional Male Volleyball Players. International Journal of Sports Physiology and Performance 11(1):116–121. doi:10.1123/ijspp.2014-0461
94. Shockett PE, Khanal J, Sitaula A, Oglesby C, Meachum WA, Castracane VD, Kraemer RR (2016) Plasma cell free mitochondrial DNA declines in response to prolonged moderate aerobic exercise. Physiological Reports 4(1):e12672. doi:10.14814/phy2.12672
95. Kandel ES (2012) Mutations in circulating mitochondrial DNA: Cassandra of oral cancer? Oncotarget 3(7):664–665. doi:10.18632/oncotarget.567
96. Uzawa K, Baba T, Uchida F, Yamatoji M, Kasamatsu A, Sakamoto Y, Tanzawa H (2012) Circulating tumor-derived mutant mitochondrial DNA: a predictive biomarker of clinical prognosis in human squamous cell carcinoma. Oncotarget 3(7):670–677. doi:10.18632/oncotarget.523
97. Huang C-Y, Chen Y-M, Wu C-H, Tsai C-M, Lee Y-C, Perng R-P, Whang-Peng J (2014) Circulating free mitochondrial DNA concentration and its association with erlotinib treatment in patients with adenocarcinoma of the lung. Oncology Letters 7(6):2180–2184. doi:10.3892/ol.2014.2006
98. Zhang Q, Raoof M, Chen Y, Sumi Y, Sursal T, Junger W, Hauser CJ (2010) Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature 464(7285):104–107. doi:10.1038/nature08780
99. Cao H, Ye H, Sun Z, Shen X, Song Z, Wu X, Yang J (2014) Circulatory Mitochondrial DNA Is a Pro-Inflammatory Agent in Maintenance Hemodialysis Patients. PLoS ONE 9(12):e113179. doi:10.1371/journal.pone.0113179
100. Itagaki K, Kaczmarek E, Lee YT, Tang IT, Isal B, Adibnia Y, Hauser CJ (2015) Mitochondrial DNA released by trauma induces neutrophil extracellular traps. PloS One 10(3):e0120549. doi:10.1371/journal.pone.0120549
101. Cools-Lartigue J, Spicer J, McDonald B, Gowing S, Chow S, Giannias B, Ferri L (2013) Neutrophil extracellular traps sequester circulating tumor cells and promote metastasis. The Journal of Clinical Investigation. doi:10.1172/JCI67484
102. Tohme S, Yazdani HO, Al-Khafaji AB, Chidi AP, Loughran P, Mowen K, Tsung A (2016) Neutrophil Extracellular Traps Promote the Development and Progression of Liver Metastases after Surgical Stress. Cancer Research. doi:10.1158/0008-5472.CAN-15-1591
103. Yu M (2011) Generation, function and diagnostic value of mitochondrial DNA copy number alterations in human cancers. Life Sciences 89(3–4):65–71. doi:10.1016/j.lfs.2011.05.010
104. Yu M (2012) Somatic mitochondrial DNA mutations in human cancers. Advances in Clinical Chemistry 57:99–138
105. Chatterjee A, Mambo E, Sidransky D (2006) Mitochondrial DNA mutations in human cancer. Oncogene 25(34):4663–4674. doi:10.1038/sj.onc.1209604
106. Lu H, Busch J, Jung M, Rabenhorst S, Ralla B, Kilic E, Jung K (2016) Diagnostic and prognostic potential of circulating cell-free genomic and mitochondrial DNA fragments in clear cell renal cell carcinoma patients. Clinica Chimica Acta 452:109–119. doi:10.1016/j.cca.2015.11.009
107. Jiang P, Chan CWM, Chan KCA, Cheng SH, Wong J, Wong VW-S, Lo YMD (2015) Lengthening and shortening of plasma DNA in hepatocellular carcinoma patients. Proceedings of the National Academy of Sciences of the United States of America 112(11):E1317–1325. doi:10.1073/pnas.1500076112
108. Jahr S, Hentze H, Englisch S, Hardt D, Fackelmayer FO, Hesch RD, Knippers R (2001) DNA fragments in the blood plasma of cancer patients: quantitations and evidence for their origin from apoptotic and necrotic cells. Cancer Research 61(4):1659–1665
109. Snyder MW, Kircher M, Hill AJ, Daza RM, Shendure J (2016) Cell-free DNA Comprises an In Vivo Nucleosome Footprint that Informs Its Tissues-Of-Origin. Cell 164(1–2):57–68. doi:10.1016/j.cell.2015.11.050
110. Lehmann-Werman R, Neiman D, Zemmour H, Moss J, Magenheim J, Vaknin-Dembinsky A, Dor Y (2016) Identification of tissue-specific cell death using methylation patterns of circulating DNA. Proceedings of the National Academy of Sciences of the United States of America. doi:10.1073/pnas.1519286113
111. Nagata S, Nagase H, Kawane K, Mukae N, Fukuyama H (2003) Degradation of chromosomal DNA during apoptosis. Cell Death and Differentiation 10(1):108–116. doi:10.1038/sj.cdd.4401161
112. Holdenrieder S, Stieber P, Bodenmüller H, Busch M, Von Pawel J, Schalhorn A, Seidel D (2001) Circulating Nucleosomes in Serum. Annals of the New York Academy of Sciences 945(1):93–102. doi:10.1111/j.1749-6632.2001.tb03869.x
113. Holdenrieder S, Stieber P (2009) Clinical use of circulating nucleosomes. Critical Reviews in Clinical Laboratory Sciences 46(1):1–24. doi:10.1080/10408360802485875
114. Weerasinghe P, Buja LM (2012) Oncosis: an important non-apoptotic mode of cell death. Experimental and Molecular Pathology 93(3):302–308. doi:10.1016/j.yexmp.2012.09.018
115. Gezer U, Holdenrieder S (2014) Post-translational histone modifications in circulating nucleosomes as new biomarkers in colorectal cancer. In Vivo (Athens, Greece) 28(3):287–292
116. D’Souza-Schorey C, Clancy JW (2012) Tumor-derived microvesicles: shedding light on novel microenvironment modulators and prospective cancer biomarkers. Genes & Development 26(12):1287–1299. doi:10.1101/gad.192351.112
117. Lee Y, El Andaloussi S, Wood MJA (2012) Exosomes and microvesicles: extracellular vesicles for genetic information transfer and gene therapy. Human Molecular Genetics 21(R1):R125–134. doi:10.1093/hmg/dds317
118. Turturici G, Tinnirello R, Sconzo G, Geraci F (2014) Extracellular membrane vesicles as a mechanism of cell-to-cell communication: advantages and disadvantages. American Journal of Physiology - Cellular Physiology 306(7):C621–633. doi:10.1152/ajpcell.00228.2013
119. De Jong OG, Van Balkom BWM, Schiffelers RM, Bouten CVC, Verhaar MC (2014) Extracellular vesicles: potential roles in regenerative medicine. Frontiers in Immunology 5:608. doi:10.3389/fimmu.2014.00608
120. Tetta C, Ghigo E, Silengo L, Deregibus MC, Camussi G (2013) Extracellular vesicles as an emerging mechanism of cell-to-cell communication. Endocrine 44(1):11–19. doi:10.1007/s12020-012-9839-0
121. Chevillet JR, Kang Q, Ruf IK, Briggs HA, Vojtech LN, Hughes SM, Tewari M (2014) Quantitative and stoichiometric analysis of the microRNA content of exosomes. Proceedings of the National Academy of Sciences of the United States of America 111(41):14888–14893. doi:10.1073/pnas.1408301111
122. Thakur BK, Zhang H, Becker A, Matei I, Huang Y, Costa-Silva B, Lyden D (2014) Double-stranded DNA in exosomes: a novel biomarker in cancer detection. Cell Research 24(6):766–769. doi:10.1038/cr.2014.44
123. Chistiakov DA, Chekhonin VP (2014) Extracellular vesicles shed by glioma cells: pathogenic role and clinical value. Tumour Biology 35(9):8425–8438. doi:10.1007/s13277-014-2262-9
124. Lowe SW, Lin AW (2000) Apoptosis in cancer. Carcinogenesis 21(3):485–495
125. Vlassov VV, Laktionov PP, Rykova EY (2007) Extracellular nucleic acids. BioEssays 29(7):654–667. doi:10.1002/bies.20604
126. Rogers JC (1976) Characterization of DNA excreted from phytohemagglutinin-stimulated lymphocytes. The Journal of Experimental Medicine 143(5):1249–1264
127. Boldt DH, MacDermott RP, Speckart SF, Nash GS (1977) Excretion of DNA by purified human lymphocyte subpopulations. Journal of Immunology (Baltimore, Md: 1950) 118(4):1495–1498
128. Hoessli DC, Jones AP, Eisenstadt JM, Waksman BH (1977) Studies on DNA release by cultured rat lymphoblasts. International Archives of Allergy and Applied Immunology 54(6):517–528
129. Olsen I, Harris G (1974) Uptake and release of DNA by lymphoid tissue and cells. Immunology 27(6):973–987
130. Stroun, M., Anker, P., Gahan, P. B., & Henri, J. (1977). Spontaneous release of newly synthesized DNA from frog auricles. Archives des Sciences.
131. Stroun M, Anker P, Beljanski M, Henri J, Lederrey C, Ojha M, Maurice PA (1978) Presence of RNA in the nucleoprotein complex spontaneously released by human lymphocytes and frog auricles in culture. Cancer Research 38(10):3546–3554
132. Adams DH, Gahan PB (1983) The DNA extruded by rat spleen cells in culture. The International Journal of Biochemistry 15(4):547–552
133. Adams DH, McIntosh AA (1985) Studies on the cytosolic DNA of chick embryo fibroblasts and its uptake by recipient cultured cells. The International Journal of Biochemistry 17(10):1041–1051
134. McIntosh AA, Adams DH (1985) Further studies on the extrusion of cytosol macromolecules by cultured chick embryo fibroblast cells. The International Journal of Biochemistry 17(2):147–153
135. Challen C, Adams DH (1987) The assembly of the DNA complex present in chick embryo cell cytosol. The International Journal of Biochemistry 19(3):235–243
136. Ochatt, S., Gahan, P. (2005). Viable protoplasts release newly synthesised DNA. In: COST 843 action: “Quality enhancement of plant production throught tissue culture”, COST 851 Action “Gametic cells and molecular breeding for crops improvement” (p. 218–219).
137. Adams DH, Diaz N, Gahan PB (1997) In vitro stimulation by tumour cell media of [3H]-thymidine incorporation by mouse spleen lymphocytes. Cell Biochemistry and Function 15(2):119–126. doi:10.1002/(SICI)1099-0844(19970601)15:2<119::AID-CBF731>3.0.CO;2-C
138. Kim J, Bae J-S (2016) Tumor-Associated Macrophages and Neutrophils in Tumor Microenvironment. Mediators of Inflammation 2016:6058147. doi:10.1155/2016/6058147
139. Berger-Achituv S, Brinkmann V, Abed UA, Kühn LI, Ben-Ezra J, Elhasid R, Zychlinsky A (2013) A proposed role for neutrophil extracellular traps in cancer immunoediting. Frontiers in Immunology 4:48. doi:10.3389/fimmu.2013.00048
140. Mishalian I, Bayuh R, Levy L, Zolotarov L, Michaeli J, Fridlender ZG (2013) Tumor-associated neutrophils (TAN) develop pro-tumorigenic properties during tumor progression. Cancer Immunology, Immunotherapy 62(11):1745–1756. doi:10.1007/s00262-013-1476-9
141. Fridlender ZG, Albelda SM (2012) Tumor Associated Neutrophils: Friend or Foe? Carcinogenesis. doi:10.1093/carcin/bgs123
142. Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS, Zychlinsky A (2004) Neutrophil extracellular traps kill bacteria. Science (New York, NY) 303(5663):1532–1535. doi:10.1126/science.1092385
143. Branzk N, Papayannopoulos V (2013) Molecular mechanisms regulating NETosis in infection and disease. Seminars in Immunopathology 35(4):513–530. doi:10.1007/s00281-013-0384-6
144. Papayannopoulos V, Metzler KD, Hakkim A, Zychlinsky A (2010) Neutrophil elastase and myeloperoxidase regulate the formation of neutrophil extracellular traps. The Journal of Cell Biology 191(3):677–691. doi:10.1083/jcb.201006052
145. Yipp BG, Kubes P (2013) NETosis: how vital is it? Blood 122(16):2784–2794. doi:10.1182/blood-2013-04-457671
146. Cooper PR, Palmer LJ, Chapple ILC (2013) Neutrophil extracellular traps as a new paradigm in innate immunity: friend or foe? Periodontology 2000 63(1):165–197. doi:10.1111/prd.12025
147. Kaplan MJ, Radic M (2012) Neutrophil extracellular traps (NETs): Double-edged swords of innate immunity. Journal of Immunology (Baltimore, Md: 1950) 189(6):2689–2695. doi:10.4049/jimmunol.1201719
148. Brinkmann V, Zychlinsky A (2012) Neutrophil extracellular traps: Is immunity the second function of chromatin? The Journal of Cell Biology 198(5):773–783. doi:10.1083/jcb.201203170
149. Luo L, Zhang S, Wang Y, Rahman M, Syk I, Zhang E, Thorlacius H (2014) Proinflammatory role of neutrophil extracellular traps in abdominal sepsis. American Journal of Physiology - Lung Cellular and Molecular Physiology 307(7):L586–596. doi:10.1152/ajplung.00365.2013
150. Fuchs TA, Brill A, Duerschmied D, Schatzberg D, Monestier M, Myers DD, Wagner DD (2010) Extracellular DNA traps promote thrombosis. Proceedings of the National Academy of Sciences 107(36):15880–15885. doi:10.1073/pnas.1005743107
151. Beiter T, Fragasso A, Hudemann J, Schild M, Steinacker J, Mooren FC, Niess AM (2014) Neutrophils release extracellular DNA traps in response to exercise. Journal of Applied Physiology (Bethesda, Md: 1985) 117(3):325–333. doi:10.1152/japplphysiol.00173.2014
152. Davis BP, Rothenberg ME (2014) Eosinophils and cancer. Cancer Immunology Research 2(1):1–8. doi:10.1158/2326-6066.CIR-13-0196
153. Yousefi S, Simon D, Simon H-U (2012) Eosinophil extracellular DNA traps: molecular mechanisms and potential roles in disease. Current Opinion in Immunology 24(6):736–739. doi:10.1016/j.coi.2012.08.010
154. Yousefi S, Gold JA, Andina N, Lee JJ, Kelly AM, Kozlowski E, Simon H-U (2008) Catapult-like release of mitochondrial DNA by eosinophils contributes to antibacterial defense. Nature Medicine 14(9):949–953. doi:10.1038/nm.1855
155. Rakoff-Nahoum S (2006) Why cancer and inflammation? The Yale Journal of Biology and Medicine 79(3–4):123–130
156. Chelobanov BP, Laktionov PP, Vlasov VV (2006) Proteins involved in binding and cellular uptake of nucleic acids. Biochemistry. Biokhimiia 71(6):583–596
157. Rykova EY, Pautova LV, Yakubov LA, Karamyshev VN, Vlassov VV (1994) Serum immunoglobulins interact with oligonucleotides. FEBS Letters 344(1):96–98
158. Bryzgunova OE, Tamkovich SN, Cherepanova AV, Yarmoshchuk SV, Permyakova VI, Anykeeva OY, Laktionov PP (2015) Redistribution of Free- and Cell-Surface-Bound DNA in Blood of Benign and Malignant Prostate Tumor Patients. Acta Naturae 7(2):115–118
159. Morozkin ES, Laktionov PP, Rykova EY, Vlassov VV (2004) Extracellular nucleic acids in cultures of long-term cultivated eukaryotic cells. Annals of the New York Academy of Sciences 1022:244–249. doi:10.1196/annals.1318.038
160. Schwarzenbach H, Hoon DSB, Pantel K (2011) Cell-free nucleic acids as biomarkers in cancer patients. Nature reviews. Cancer 11(6):426–437. doi:10.1038/nrc3066
161. van der Vaart M, Pretorius PJ (2010) Is the role of circulating DNA as a biomarker of cancer being prematurely overrated? Clinical Biochemistry 43(1–2):26–36. doi:10.1016/j.clinbiochem.2009.08.027
162. El Messaoudi S, Rolet F, Mouliere F, Thierry AR (2013) Circulating cell free DNA: Preanalytical considerations. Clinica Chimica Acta. doi:10.1016/j.cca.2013.05.022
163. El Messaoudi S, Thierry AR (2015) Pre-analytical Requirements for Analyzing Nucleic Acids from Blood. In: Gahan PB (ed) Circulating Nucleic Acids in Early Diagnosis, Prognosis and Treatment Monitoring, vol 5. Springer Netherlands, Dordrecht, pp 45–69, Retrieved from http://link.springer.com/10.1007/978-94-017-9168-7_3
164. Gormally E, Caboux E, Vineis P, Hainaut P (2007) Circulating free DNA in plasma or serum as biomarker of carcinogenesis: practical aspects and biological significance. Mutation Research 635(2–3):105–117. doi:10.1016/j.mrrev.2006.11.002
165. Wang BG, Huang H-Y, Chen Y-C, Bristow RE, Kassauei K, Cheng C-C, Shih I-M (2003) Increased plasma DNA integrity in cancer patients. Cancer Research 63(14):3966–3968
166. Pang D, Thierry AR, Dritschilo A (2015) DNA studies using atomic force microscopy: capabilities for measurement of short DNA fragments. Frontiers in Molecular Biosciences 2:1. doi:10.3389/fmolb.2015.00001
167. Lo YM, Zhang J, Leung TN, Lau TK, Chang AM, Hjelm NM (1999) Rapid clearance of fetal DNA from maternal plasma. American Journal of Human Genetics 64(1):218–224. doi:10.1086/302205
168. Yu SCY, Lee SWY, Jiang P, Leung TY, Chan KCA, Chiu RWK, Lo YMD (2013) High-resolution profiling of fetal DNA clearance from maternal plasma by massively parallel sequencing. Clinical Chemistry 59(8):1228–1237. doi:10.1373/clinchem.2013.203679
169. Diehl F, Schmidt K, Choti MA, Romans K, Goodman S, Li M, Diaz LA (2008) Circulating mutant DNA to assess tumor dynamics. Nature Medicine 14(9):985–990. doi:10.1038/nm.1789
170. Stroun M, Anker P (2006) Prehistory of the notion of circulating nucleic acids in plasma/serum (CNAPS): birth of a hypothesis. Annals of the New York Academy of Sciences 1075:10–20. doi:10.1196/annals.1368.002
171. Stroun, M. (2011). Reflections on a Life of CNAPS: From Circulating DNA to the Virtosome. In P. B. Gahan (Ed.), Circulating Nucleic Acids in Plasma and Serum (pp. 15–20). Springer Netherlands. Retrieved from http://link.springer.com/chapter/10.1007/978-90-481-9382-0_2
172. Anker P, Stroun M (2012) Circulating nucleic acids and evolution. Expert Opinion on Biological Therapy 12(Suppl 1):S113–117. doi:10.1517/14712598.2012.666520
173. Darwin C (1876) Animals and Plants under domestication. Vol II, 2nd edn. Appleton & Company, New York
174. Liu Y (2006) Historical and modern genetics of plant graft hybridization. Advances in Genetics 56:101–129. doi:10.1016/S0065-2660(06)56003-1
175. Liu Y (2008) A new perspective on Darwin’s Pangenesis. Biological Reviews of the Cambridge Philosophical Society 83(2):141–149. doi:10.1111/j.1469-185X.2008.00036.x
176. Stroun J, Stroun-Guttieres L, Rossi J, Stroun M (1962) Alteration of the color of the feathers in white Leghorn chickens by repeated injections of the blood of guinea hens. Observations on 5 generations. Comptes Rendus Hebdomadaires des Séances de l'Académie des Sciences 255:781–783
177. Stroun, M., Mathon, C. C., & Stroun, J. (1963). Alteration of hereditary traits in Solanum melongena induced by grafts with Solanum nigrum. In: Proceedings of the 11th International Congress of Genetics (la Haye) (Vol. 1, p. 218).
178. Gahan PB (2003) Messenger DNA in higher plants. Cell Biochemistry and Function 21(3):207–209. doi:10.1002/cbf.1074
179. Stroun M, Anker P (1972) In vitro synthesis of DNA spontaneously released by bacteria or frog auricles. Biochimie 54(11):1443–1452
180. Thierry AR, Dritschilo A (1992) Intracellular availability of unmodified, phosphorothioated and liposomally encapsulated oligodeoxynucleotides for antisense activity. Nucleic Acids Research 20(21):5691–5698
181. Anker P, Lyautey J, Lefort F, Lederrey C, Stroun M (1994) Transformation de cellules NIH/3 T3 et cellules SW 480 porteuses d’une mutation K-ras. Comptes Rendus de l'Academie des Sciences Serie III, Sciences de la Vie 317(10):869–874
182. Anker P, Jachertz D, Stroun M, Brögger R, Lederrey C, Maurice PA (1979) [Transfer of genetic information from T to B human lymphocytes during an immune response to herpes simplex virus]. Comptes Rendus Des Séances De l’Académie Des Sciences Série D, Sciences Naturelles 289(2):217–220
183. Anker P, Jachertz D, Stroun M, Brögger R, Lederrey C, Henri J, Maurice PA (1980) The role of extracellular DNA in the transfer of information from T to B human lymphocytes in the course of an immune response. Journal of Immunogenetics 7(6):475–481
184. Anker P, Jachertz D, Maurice PA, Stroun M (1984) Nude mice injected with DNA released by antigen stimulated human T lymphocytes produce specific antibodies expressing human characteristics. Cell Biochemistry and Function 2(1):33–37. doi:10.1002/cbf.290020110
185. Anker P, Stroun M, Maurice PA (1976) Spontaneous extracellular synthesis of DNA released by human blood lymphocytes. Cancer Research 36(8):2832–2839
186. Anker P, Stroun M, Maurice P (1977) Characteristics of nucleic acids excreted by non-stimulated normal human lymphocytes. Schweizerische Medizinische Wochenschrift 107(41):1457
187. Anker P, Stroun M (2006) Immunological aspects of circulating DNA. Annals of the New York Academy of Sciences 1075:34–39. doi:10.1196/annals.1368.004
188. Jachertz, D., Stroun, M., Anker, P., Brogger, R., Lederrey, C., & Maurice, P. A. (1979). Transfer of genetic information from T to B lymphocytes in the course of an immune response. Biomedicine/[publiée Pour l’A.A.I.C.I.G.], 31(6), 153–154.
189. Bendich A, Wilczok T, Borenfreund E (1965) Circulating DNA as a possible factor in oncogenesis. Science (New York, NY) 148(3668):374–376
190. García-Olmo DC, Domínguez C, García-Arranz M, Anker P, Stroun M, García-Verdugo JM, García-Olmo D (2010) Cell-free nucleic acids circulating in the plasma of colorectal cancer patients induce the oncogenic transformation of susceptible cultured cells. Cancer Research 70(2):560–567. doi:10.1158/0008-5472.CAN-09-3513
191. García-Olmo DC, García-Olmo D (2013) Biological role of cell-free nucleic acids in cancer: the theory of genometastasis. Critical Reviews in Oncogenesis 18(1–2):153–161
192. García-Olmo DC, Picazo MG, García-Olmo D (2012) Transformation of non-tumor host cells during tumor progression: theories and evidence. Expert Opinion on Biological Therapy 12(Suppl 1):S199–207. doi:10.1517/14712598.2012.681370
193. Peters DL, Pretorius PJ (2012) Continuous adaptation through genetic communication - a putative role for cell-free DNA. Expert Opinion on Biological Therapy 12(Suppl 1):S127–132. doi:10.1517/14712598.2012.668518
194. Hariton-Gazal E, Rosenbluh J, Graessmann A, Gilon C, Loyter A (2003) Direct translocation of histone molecules across cell membranes. Journal of Cell Science 116(Pt 22):4577–4586. doi:10.1242/jcs.00757
195. Mittra I, Khare NK, Raghuram GV, Chaubal R, Khambatti F, Gupta D, Dutt A (2015) Circulating nucleic acids damage DNA of healthy cells by integrating into their genomes. Journal of Biosciences 40(1):91–111
196. Mittra I (2015) Circulating nucleic acids: a new class of physiological mobile genetic elements. F1000Research 4:924. doi:10.12688/f1000research.7095.1
197. Gahan PB, Anker P, Stroun M, Jacob K (1969) DNA-Induced Chromosome Damage in Vicia Faba. Caryologia 22(4):307–310. doi:10.1080/00087114.1969.10796349
198. Gahan PB, Perry IJ, Stroun M, Anker P (1974) Effect of Exogenous DNA on Acid Deoxyribonuclease Activity in Intact Roots of Vicia faba L. Annals of Botany 38(3):701–704
199. Klieve AV, Yokoyama MT, Forster RJ, Ouwerkerk D, Bain PA, Mawhinney EL (2005) Naturally occurring DNA transfer system associated with membrane vesicles in cellulolytic Ruminococcus spp. of ruminal origin. Applied and Environmental Microbiology 71(8):4248–4253. doi:10.1128/AEM.71.8.4248-4253.2005
200. de la Cruz F, Davies J (2000) Horizontal gene transfer and the origin of species: lessons from bacteria. Trends in Microbiology 8(3):128–133
201. Moriguchi K, Yamamoto S, Tanaka K, Kurata N, Suzuki K (2013) Trans-kingdom horizontal DNA transfer from bacteria to yeast is highly plastic due to natural polymorphisms in auxiliary nonessential recipient genes. PloS One 8(9):e74590. doi:10.1371/journal.pone.0074590
202. Heinemann JA, Sprague GF (1989) Bacterial conjugative plasmids mobilize DNA transfer between bacteria and yeast. Nature 340(6230):205–209. doi:10.1038/340205a0
203. Syvanen M (1985) Cross-species gene transfer; implications for a new theory of evolution. Journal of Theoretical Biology 112(2):333–343
204. Jabr, F. (n.d.). Genes that jump species: does this shake the tree of life? — Ferris Jabr — Aeon Essays. Aeon. Retrieved March 16, 2016, from https://aeon.co/essays/genes-that-jump-species-does-this-shake-the-tree-of-life.
205. Stroun M, Anker P, Gahan P. B and Sheikh K. (1971). Bacterial infection due to natural release of nucleic acids from bacteria in plant cells. Informative Molecules in Biological Systems, 187–192.
206. Anker P, Stroun M, Laroche J (1972) Bacterial RNA synthesis in frog auricles after intraperitoneal injection of bacteria. Experientia 28(4):488–489. doi:10.1007/BF02008360
207. Pisetsky DS (2012) The origin and properties of extracellular DNA: from PAMP to DAMP. Clinical Immunology (Orlando, Fla) 144(1):32–40. doi:10.1016/j.clim.2012.04.006
208. Kawasaki T, Kawai T, Akira S (2011) Recognition of nucleic acids by pattern-recognition receptors and its relevance in autoimmunity. Immunological Reviews 243(1):61–73. doi:10.1111/j.1600-065X.2011.01048.x
209. Napirei M, Karsunky H, Zevnik B, Stephan H, Mannherz HG, Möröy T (2000) Features of systemic lupus erythematosus in Dnase1-deficient mice. Nature Genetics 25(2):177–181. doi:10.1038/76032
210. Jacob M, Napirei M, Ricken A, Dixkens C, Mannherz HG (2002) Histopathology of lupus-like nephritis in Dnase1-deficient mice in comparison to NZB/W F1 mice. Lupus 11(8):514–527
211. Martinez-Valle F, Balada E, Ordi-Ros J, Bujan-Rivas S, Sellas-Fernandez A, Vilardell-Tarres M (2009) DNase 1 activity in patients with systemic lupus erythematosus: relationship with epidemiological, clinical, immunological and therapeutical features. Lupus 18(5):418–423. doi:10.1177/0961203308098189
212. Chitrabamrung S, Rubin RL, Tan EM (1981) Serum deoxyribonuclease I and clinical activity in systemic lupus erythematosus. Rheumatology International 1(2):55–60
213. Kawai T, Akira S (2010) The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nature Immunology 11(5):373–384. doi:10.1038/ni.1863
214. Pisetsky DS, Ullal AJ (2010) The blood nucleome in the pathogenesis of SLE. Autoimmunity Reviews 10(1):35–37. doi:10.1016/j.autrev.2010.07.007
215. Klinman DM (2004) Immunotherapeutic uses of CpG oligodeoxynucleotides. Nature Reviews Immunology 4(4):249–259. doi:10.1038/nri1329
216. Margulis L (1975) Symbiotic theory of the origin of eukaryotic organelles; criteria for proof. Symposia of the Society for Experimental Biology 29:21–38
217. McCarthy CG, Wenceslau CF, Goulopoulou S, Ogbi S, Baban B, Sullivan JC, Webb RC (2015) Circulating mitochondrial DNA and Toll-like receptor 9 are associated with vascular dysfunction in spontaneously hypertensive rats. Cardiovascular Research 107(1):119–130. doi:10.1093/cvr/cvv137
218. Lewis EJ, Schwartz MM (2005) Pathology of lupus nephritis. Lupus 14(1):31–38
219. Scharfe-Nugent A, Corr SC, Carpenter SB, Keogh L, Doyle B, Martin C, O’Neill LAJ (2012) TLR9 provokes inflammation in response to fetal DNA: mechanism for fetal loss in preterm birth and preeclampsia. Journal of Immunology (Baltimore, Md: 1950) 188(11):5706–5712. doi:10.4049/jimmunol.1103454
220. Cotter AM, Martin CM, O’leary JJ, Daly SF (2004) Increased fetal DNA in the maternal circulation in early pregnancy is associated with an increased risk of preeclampsia. American Journal of Obstetrics and Gynecology 191(2):515–520. doi:10.1016/j.ajog.2004.01.040
221. Seval MM, Karabulut HG, Tükün A, Koç A (2015) Cell free fetal DNA in the plasma of pregnant women with preeclampsia. Clinical and Experimental Obstetrics & Gynecology 42(6):787–791
222. Wartha F, Beiter K, Normark S, Henriques-Normark B (2007) Neutrophil extracellular traps: casting the NET over pathogenesis. Current Opinion in Microbiology 10(1):52–56. doi:10.1016/j.mib.2006.12.005
223. Zawrotniak M, Rapala-Kozik M (2013) Neutrophil extracellular traps (NETs) - formation and implications. Acta Biochimica Polonica 60(3):277–284
224. Demers M, Wagner DD (2013) Neutrophil extracellular traps: A new link to cancer-associated thrombosis and potential implications for tumor progression. Oncoimmunology 2(2):e22946. doi:10.4161/onci.22946
225. Spicer JD, McDonald B, Cools-Lartigue JJ, Chow SC, Giannias B, Kubes P, Ferri LE (2012) Neutrophils promote liver metastasis via Mac-1-mediated interactions with circulating tumor cells. Cancer Research 72(16):3919–3927. doi:10.1158/0008-5472.CAN-11-2393
226. McDonald B, Spicer J, Giannais B, Fallavollita L, Brodt P, Ferri LE (2009) Systemic inflammation increases cancer cell adhesion to hepatic sinusoids by neutrophil mediated mechanisms. International Journal of Cancer 125(6):1298–1305. doi:10.1002/ijc.24409
227. Hawes MC, Wen F, Elquza E (2015) Extracellular DNA: A Bridge to Cancer. Cancer Research 75(20):4260–4264. doi:10.1158/0008-5472.CAN-15-1546
228. Patutina O, Mironova N, Ryabchikova E, Popova N, Nikolin V, Kaledin V, Zenkova M (2011) Inhibition of metastasis development by daily administration of ultralow doses of RNase A and DNase I. Biochimie 93(4):689–696. doi:10.1016/j.biochi.2010.12.011
229. Patutina OA, Mironova NL, Ryabchikova EI, Popova NA, Nikolin VP, Kaledin VI, Zenkova MA (2010) Tumoricidal Activity of RNase A and DNase I. Acta Naturae 2(1):88–94
230. Trejo-Becerril C, Pérez-Cárdenas E, Taja-Chayeb L, Anker P, Herrera-Goepfert R, Medina-Velázquez LA, Dueñas-González A (2012) Cancer progression mediated by horizontal gene transfer in an in vivo model. PloS One 7(12):e52754. doi:10.1371/journal.pone.0052754
231. Lee J, Sohn JW, Zhang Y, Leong KW, Pisetsky D, Sullenger BA (2011) Nucleic acid-binding polymers as anti-inflammatory agents. Proceedings of the National Academy of Sciences of the United States of America 108(34):14055–14060. doi:10.1073/pnas.1105777108
232. Holl EK, Shumansky KL, Pitoc G, Ramsburg E, Sullenger BA (2013) Nucleic acid scavenging polymers inhibit extracellular DNA-mediated innate immune activation without inhibiting anti-viral responses. PloS One 8(7):e69413. doi:10.1371/journal.pone.0069413
233. Stroun, M. (2012). “Mon cher collègue je ne serai pas recteur”: Une aventure dans le monde de l’Université et de la recherche scientifique suisse. Editions L’Harmattan.
234. Dawson S-J, Tsui DWY, Murtaza M, Biggs H, Rueda OM, Chin S-F, Rosenfeld N (2013) Analysis of Circulating Tumor DNA to Monitor Metastatic Breast Cancer. New England Journal of Medicine 368(13):1199–1209. doi:10.1056/NEJMoa1213261
235. Misale S, Yaeger R, Hobor S, Scala E, Janakiraman M, Liska D, Bardelli A (2012) Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer. Nature 486(7404):532–536. doi:10.1038/nature11156
236. Garcia-Murillas I, Schiavon G, Weigelt B, Ng C, Hrebien S, Cutts RJ, Turner NC (2015) Mutation tracking in circulating tumor DNA predicts relapse in early breast cancer. Science Translational Medicine 7(302):302ra133. doi:10.1126/scitranslmed.aab0021
237. Rago C, Huso DL, Diehl F, Karim B, Liu G, Papadopoulos N, Diaz LA (2007) Serial assessment of human tumor burdens in mice by the analysis of circulating DNA. Cancer Research 67(19):9364–9370. doi:10.1158/0008-5472.CAN-07-0605
238. Diaz LA Jr, Williams RT, Wu J, Kinde I, Hecht JR, Berlin J, Vogelstein B (2012) The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers. Nature 486(7404):537–540. doi:10.1038/nature11219