J. , organisation du 10ème symposium international sur les acides nucléiques circulants dans le plasma et le sérum (CNAPS), et j'ai contribué à la rédaction de la revue, essentiellement dans les parties « Structures et origines tissulaires » et « Biologie ». Références : 1. P. Mandel, F. Metais, Les acides nucléiques du plasma sanguin chez l'homme

A. Bendich, T. Wilczok, and E. Borenfreund, Circulating DNA as a Possible Factor in Oncogenesis, Science, vol.148, pp.374-376, 1965.

E. M. Tan, Deoxyribonucleic Acid (DNA) and Antibodies to DNA in the Serum of Patients with Systemic Lupus Erythematosus, p.9

P. Anker and M. Stroun, Circulating DNA in plasma or serum, Medicina (B Aires), vol.60, pp.699-702, 2000.

M. Stroun and P. Anker, Nucleic acids spontaneously released by living frog auricles, Biochem. J, vol.128, pp.100-101, 1972.

S. A. Leon, B. Shapiro, D. M. Sklaroff, and M. J. Yaros, Free DNA in the serum of cancer patients and the effect of therapy, Cancer Res, vol.37, pp.646-650, 1977.

B. Shapiro, M. Chakrabarty, E. M. Cohn, and S. A. Leon, Determination of circulating DNA levels in patients with benign or malignant gastrointestinal disease, Cancer, vol.51, pp.2116-2120, 1983.

M. Stroun, P. Anker, P. Maurice, J. Lyautey, C. Lederrey et al., Neoplastic characteristics of the DNA found in the plasma of cancer patients, Oncology, vol.46, pp.318-322, 1989.

G. D. Sorenson, D. M. Pribish, F. H. Valone, V. A. Memoli, D. J. Bzik et al., Soluble normal and mutated DNA sequences from single-copy genes in human blood, Cancer Epidemiol. Biomarkers Prev, vol.3, pp.67-71, 1994.

V. Vasioukhin, P. Anker, P. Maurice, J. Lyautey, C. Lederrey et al., Point mutations of the N-ras gene in the blood plasma DNA of patients with myelodysplastic syndrome or acute myelogenous leukaemia, Br. J. Haematol, vol.86, pp.774-779, 1994.

G. Cuda, A. Gallelli, A. Nisticò, P. Tassone, V. Barbieri et al., Detection of microsatellite instability and loss of heterozygosity in serum DNA of small and non-small cell lung cancer patients: a tool for early diagnosis? Lung Cancer, vol.30, pp.211-214, 2000.

R. M. Bremnes, R. Sirera, and C. Camps, Circulating tumour-derived DNA and RNA markers in blood: a tool for early detection, diagnostics, and follow-up? Lung Cancer, vol.49, pp.1-12, 2005.

F. Diehl, M. Li, D. Dressman, Y. He, D. Shen et al., Detection and quantification of mutations in the plasma of patients with colorectal tumors, MEDICAL SCIENCES, p.6

Y. M. Lo, N. Corbetta, P. F. Chamberlain, V. Rai, I. L. Sargent et al., Presence of fetal DNA in maternal plasma and serum, Lancet, vol.350, pp.485-487, 1997.

M. Fleischhacker and B. Schmidt, Circulating nucleic acids (CNAs) and cancer-A survey, Biochimica et Biophysica Acta (BBA) -Reviews on Cancer, vol.1775, pp.181-232, 2007.

A. R. Thierry, S. E. Messaoudi, P. B. Gahan, P. Anker, and M. Stroun, Origins, structures, and functions of circulating DNA in oncology, Cancer and Metastasis Reviews, vol.35, pp.347-376, 2016.
URL : https://hal.archives-ouvertes.fr/hal-02299112

I. Mittra, N. K. Nair, and P. K. Mishra, Nucleic acids in circulation: are they harmful to the host?, J. Biosci, vol.37, pp.301-312, 2012.

P. P. Laktionov, S. N. Tamkovich, E. Y. Rykova, O. E. Bryzgunova, A. V. Starikov et al., 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, vol.1022, pp.221-227, 2004.

S. Elmore, Apoptosis: A Review of Programmed Cell Death. Toxicologic Pathology, vol.35, pp.495-516, 2007.

R. Singh, A. Letai, and K. Sarosiek, Regulation of apoptosis in health and disease: the balancing act of BCL-2 family proteins, Nat Rev Mol Cell Biol, vol.20, pp.175-193, 2019.

S. Nagata, Apoptotic DNA fragmentation, Exp. Cell Res, vol.256, pp.12-18, 2000.

K. Kawane, K. Motani, and S. Nagata, DNA Degradation and Its Defects, Cold Spring Harb Perspect Biol, vol.6, 2014.

I. C. Viorritto, N. P. Nikolov, and R. M. Siegel, Autoimmunity versus tolerance: Can dying cells tip the balance?, Clinical Immunology, vol.122, pp.125-134, 2007.

S. Nagata, H. Nagase, K. Kawane, N. Mukae, and H. Fukuyama, Degradation of chromosomal DNA during apoptosis, Cell Death & Differentiation, vol.10, p.108, 2003.

S. N. Tamkovich, V. V. Vlassov, and P. P. Laktionov, Circulating DNA in the blood and its application in medical diagnosis, Mol Biol, vol.42, pp.9-19, 2008.

P. O. Delgado, B. C. Alves, F. De-sousa-gehrke, R. K. Kuniyoshi, M. L. Wroclavski et al., Characterization of cell-free circulating DNA in plasma in patients with prostate cancer, Tumor Biol, vol.34, pp.983-986, 2013.

S. Jahr, H. Hentze, S. Englisch, D. Hardt, F. O. Fackelmayer et al., DNA Fragments in the Blood Plasma of Cancer Patients: Quantitations and Evidence for Their Origin from Apoptotic and Necrotic Cells, Cancer Res, vol.61, pp.1659-1665, 2001.

P. Rumore, B. Muralidhar, M. Lin, C. Lai, and C. R. Steinman, Haemodialysis as a model for studying endogenous plasma DNA: oligonucleosome-like structure and clearance, Clin Exp Immunol, vol.90, pp.56-62, 1992.

M. Stroun, J. Lyautey, C. Lederrey, A. Olson-sand, and P. Anker, About the possible origin and mechanism of circulating DNA: Apoptosis and active DNA release, Clinica Chimica Acta, vol.313, pp.139-142, 2001.

M. Van-der, D. V. Vaart, E. V. Semenov, V. A. Kuligina, P. J. Richter et al., Characterisation of circulating DNA by parallel tagged sequencing on the 454 platform, Clinica Chimica Acta, vol.409, pp.21-27, 2009.

A. Hochreiter-hufford and K. S. Ravichandran, Clearing the Dead: Apoptotic Cell Sensing, Recognition, Engulfment, and Digestion, Cold Spring Harb Perspect Biol, vol.5, p.8748, 2013.

J. Aucamp, A. J. Bronkhorst, C. P. Badenhorst, and P. J. Pretorius, The diverse origins of circulating cell-free DNA in the human body: a critical re-evaluation of the literature, Biological Reviews, vol.93, pp.1649-1683, 2018.

S. Holdenrieder and P. Stieber, Clinical use of circulating nucleosomes, Critical Reviews in Clinical Laboratory Sciences, vol.46, pp.1-24, 2009.

M. Leist, B. Single, A. F. Castoldi, S. Kühnle, and P. Nicotera, Intracellular Adenosine Triphosphate (ATP) Concentration: A Switch in the Decision Between Apoptosis and Necrosis, Journal of Experimental Medicine, vol.185, pp.1481-1486, 1997.

P. Syntichaki, Death by necrosis: Uncontrollable catastrophe, or is there order behind the chaos?, EMBO Reports, vol.3, pp.604-609, 2002.

N. I. Walker, B. V. Harmon, G. C. Gobé, and J. F. Kerr, Patterns of cell death, Methods Achiev Exp Pathol, vol.13, pp.18-54, 1988.

Y. Yang, G. Jiang, P. Zhang, and J. Fan, Programmed cell death and its role in inflammation, Military Medical Research, vol.2, 2015.

G. Kroemer, W. S. El-deiry, P. Golstein, M. E. Peter, D. Vaux et al., Classification of cell death: recommendations of the Nomenclature Committee on Cell Death, Cell Death & Differentiation, 2005.
URL : https://hal.archives-ouvertes.fr/hal-00407686

N. Holler, R. Zaru, O. Micheau, M. Thome, A. Attinger et al., Fas triggers an alternative, caspase-8-independent cell death pathway using the kinase RIP as effector molecule, Nat Immunol, vol.1, pp.489-495, 2000.

D. Zhang, J. Shao, J. Lin, N. Zhang, B. Lu et al., RIP3, an Energy Metabolism Regulator That Switches TNF-Induced Cell Death from Apoptosis to Necrosis, Science, vol.325, pp.332-336, 2009.

H. Wang, L. Sun, L. Su, J. Rizo, L. Liu et al., Mixed Lineage Kinase Domain-like Protein MLKL Causes Necrotic Membrane Disruption upon Phosphorylation by RIP3, Molecular Cell, vol.54, pp.133-146, 2014.

Y. K. Dhuriya and D. Sharma, Necroptosis: a regulated inflammatory mode of cell death, Journal of Neuroinflammation, vol.15, p.199, 2018.

V. Sagulenko, S. J. Thygesen, D. P. Sester, A. Idris, J. A. Cridland et al., AIM2 and NLRP3 inflammasomes activate both apoptotic and pyroptotic death pathways via ASC, Cell Death Differ, vol.20, pp.1149-1160, 2013.

T. Bergsbaken, S. L. Fink, and B. T. Cookson, Pyroptosis: host cell death and inflammation, Nat Rev Microbiol, vol.7, pp.99-109, 2009.

F. Martinon, K. Burns, and J. Tschopp, The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta, Mol. Cell, vol.10, pp.417-426, 2002.

T. Fernandes-alnemri, J. Wu, J. Yu, P. Datta, B. Miller et al., The pyroptosome: a supramolecular assembly of ASC dimers mediating inflammatory cell death via caspase-1 activation, Cell Death and Differentiation, vol.14, pp.1590-1604, 2007.

W. Jiang, M. Zahurak, D. Goldenberg, Y. Milman, H. L. Park et al., Increased plasma DNA integrity index in head and neck cancer patients, International Journal of Cancer, vol.119, pp.2673-2676, 2006.

N. Umetani, J. Kim, S. Hiramatsu, H. A. Reber, O. J. Hines et al., Increased integrity of free circulating DNA in sera of patients with colorectal or periampullary cancer: direct quantitative PCR for ALU repeats, Clin. Chem, vol.52, pp.1062-1069, 2006.

B. G. Wang, H. Huang, Y. Chen, R. E. Bristow, K. Kassauei et al., Increased Plasma DNA Integrity in Cancer Patients, Cancer Res, vol.63, pp.3966-3968, 2003.

A. V. Lichtenstein, H. S. Melkonyan, L. D. Tomei, and S. R. Umansky, Circulating Nucleic Acids and Apoptosis, Annals of the New York Academy of Sciences, vol.945, pp.239-249, 2001.

J. Choi, C. F. Reich, and D. S. Pisetsky, The role of macrophages in the in vitro generation of extracellular DNA from apoptotic and necrotic cells, Immunology, vol.115, pp.55-62, 2005.

V. Brinkmann, U. Reichard, C. Goosmann, B. Fauler, Y. Uhlemann et al., Neutrophil Extracellular Traps Kill Bacteria. Science, vol.303, pp.1532-1535, 2004.

N. Branzk and V. Papayannopoulos, Molecular mechanisms regulating NETosis in infection and disease, Semin Immunopathol, vol.35, pp.513-530, 2013.

T. A. Fuchs, U. Abed, C. Goosmann, R. Hurwitz, I. Schulze et al., Novel cell death program leads to neutrophil extracellular traps, The Journal of Cell Biology, vol.176, pp.231-241, 2007.

B. G. Yipp and P. Kubes, NETosis: how vital is it?, Blood, vol.122, pp.2784-2794, 2013.

V. Papayannopoulos, Neutrophil extracellular traps in immunity and disease, Nature Reviews Immunology, vol.18, pp.134-147, 2018.

S. Yousefi, C. Mihalache, E. Kozlowski, I. Schmid, and H. U. Simon, Viable neutrophils release mitochondrial DNA to form neutrophil extracellular traps, Cell Death and Differentiation, vol.16, pp.1438-1444, 2009.

D. M. Boe, B. J. Curtis, M. M. Chen, J. A. Ippolito, and E. J. Kovacs, Extracellular traps and macrophages: new roles for the versatile phagocyte, Journal of Leukocyte Biology, vol.97, pp.1023-1035, 2015.

V. Brinkmann and A. Zychlinsky, Neutrophil extracellular traps: Is immunity the second function of chromatin?, J Cell Biol, vol.198, pp.773-783, 2012.

J. Cools-lartigue, J. Spicer, B. Mcdonald, S. Gowing, S. Chow et al., Neutrophil extracellular traps sequester circulating tumor cells and promote metastasis, J Clin Invest, vol.123, pp.3446-3458, 2013.

L. Luo, S. Zhang, Y. Wang, M. Rahman, I. Syk et al., Proinflammatory role of neutrophil extracellular traps in abdominal sepsis, American Journal of Physiology-Lung Cellular and Molecular Physiology, vol.307, pp.586-596, 2014.

T. A. Fuchs, A. Brill, D. Duerschmied, D. Schatzberg, M. Monestier et al., Extracellular DNA traps promote thrombosis, PNAS, vol.107, pp.15880-15885, 2010.

M. J. Kaplan and M. Radic, Neutrophil Extracellular Traps: Double-Edged Swords of Innate Immunity, The Journal of Immunology, vol.189, pp.2689-2695, 2012.

T. Beiter, A. Fragasso, J. Hudemann, M. Schild, J. Steinacker et al., Neutrophils release extracellular DNA traps in response to exercise, Journal of Applied Physiology, vol.117, pp.325-333, 2014.

F. Wartha and B. Henriques-normark, ETosis: A Novel Cell Death Pathway. Sci. Signal, vol.1, pp.25-25, 2008.

S. Yousefi, J. A. Gold, N. Andina, J. J. Lee, A. M. Kelly et al., Catapult-like release of mitochondrial DNA by eosinophils contributes to antibacterial defense, Nature Medicine, vol.14, pp.949-953, 2008.

S. Yousefi, D. Simon, and H. Simon, Eosinophil extracellular DNA traps: molecular mechanisms and potential roles in disease, Current Opinion in Immunology, vol.24, pp.736-739, 2012.

J. C. Rogers, D. Boldt, S. Kornfeld, S. A. Skinner, and C. R. Valeri, Excretion of Deoxyribonucleic Acid by Lymphocytes Stimulated with Phytohemagglutinin or Antigen, Proc Natl Acad Sci U S A, vol.69, pp.1685-1689, 1972.

P. Anker, M. Stroun, and P. Maurice, Spontaneous release of DNA by human blood lymphocytes as shown in an in vitro system, Cancer Res, 1975.

D. H. Adams and P. B. Gahan, Stimulated and non-stimulated rat spleen cells release different DNA-complexes, Differentiation, vol.22, pp.47-52, 1982.

D. H. Adams and A. A. Mcintosh, Studies on the cytosolic DNA of chick embryo fibroblasts and its uptake by recipient cultured cells, Int. J. Biochem, vol.17, pp.1041-1051, 1985.

D. H. Adams and A. A. Mcintosh, The cytosol origin of macromolecules extruded by cultured chick embryo fibroblast cells, Int. J. Biochem, vol.16, pp.721-726, 1984.

C. Challen and D. H. Adams, Further studies on the size and composition of the chick embryo fibroblast cytosolic DNA complex, Int. J. Biochem, vol.18, pp.423-429, 1986.

M. Stroun, P. Anker, M. Beljanski, J. Henri, C. Lederrey et al., Presence of RNA in the nucleoprotein complex spontaneously released by human lymphocytes and frog auricles in culture, Cancer Res, vol.38, pp.3546-3554, 1978.

P. B. Gahan and M. Stroun, The virtosome-a novel cytosolic informative entity and intercellular messenger, Cell Biochem. Funct, vol.28, pp.529-538, 2010.

S. R. Pelc, Turnover of DNA and function, Nature, vol.219, pp.162-163, 1968.

P. B. Gahan, P. Anker, and M. Stroun, Metabolic DNA as the origin of spontaneously released DNA?, Ann. N. Y. Acad. Sci, vol.1137, pp.7-17, 2008.

P. Anker, D. Jachertz, M. Stroun, R. Brögger, C. Lederrey et al., The role of extracellular DNA in the transfer of information from T to B human lymphocytes in the course of an immune response, J. Immunogenet, vol.7, pp.475-481, 1980.

P. Anker, J. Lyautey, F. Lefort, C. Lederrey, and M. Stroun, Transformation of NIH/3T3 cells and SW 480 cells displaying K-ras mutation

, C. R. Acad. Sci. III, Sci. Vie, vol.317, pp.869-874, 1994.

A. J. Bronkhorst, J. F. Wentzel, J. Aucamp, E. Van-dyk, L. Plessis et al., Characterization of the cell-free DNA released by cultured cancer cells, Biochimica et Biophysica Acta (BBA) -Molecular Cell Research, vol.1863, pp.157-165, 2016.

E. Van-der-pol, A. N. Boing, P. Harrison, A. Sturk, and R. Nieuwland, Classification, Functions, and Clinical Relevance of Extracellular Vesicles, Pharmacological Reviews, vol.64, pp.676-705, 2012.

B. L. Deatherage and B. T. Cookson, Membrane Vesicle Release in Bacteria, Eukaryotes, and Archaea: a Conserved yet Underappreciated Aspect of Microbial Life, Infection and Immunity, vol.80, pp.1948-1957, 2012.

G. Van-niel, G. Angelo, and G. Raposo, Shedding light on the cell biology of extracellular vesicles, Nature Reviews Molecular Cell Biology, vol.19, p.213, 2018.
URL : https://hal.archives-ouvertes.fr/hal-02359760

B. György, T. G. Szabó, M. Pásztói, Z. Pál, P. Misják et al., Membrane vesicles, current state-of-the-art: emerging role of extracellular vesicles, Cell. Mol. Life Sci, vol.68, pp.2667-2688, 2011.

D. Turpin, M. Truchetet, B. Faustin, J. Augusto, C. Contin-bordes et al., Role of extracellular vesicles in autoimmune diseases, Autoimmunity Reviews, vol.15, pp.174-183, 2016.

A. Latifkar, Y. H. Hur, J. C. Sanchez, R. A. Cerione, and M. A. Antonyak, New insights into extracellular vesicle biogenesis and function, Journal of Cell Science, vol.132, p.222406, 2019.

S. L. Maas, X. O. Breakefield, and A. M. Weaver, Extracellular Vesicles: Unique Intercellular Delivery Vehicles, Trends Cell Biol, vol.27, pp.172-188, 2017.

M. Mathieu, L. Martin-jaular, G. Lavieu, and C. Théry, Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication, Nat. Cell Biol, vol.21, pp.9-17, 2019.
URL : https://hal.archives-ouvertes.fr/inserm-02450845

M. Yáñez-mó, P. R. Siljander, Z. Andreu, A. B. Zavec, F. E. Borràs et al., J Extracell Vesicles, vol.4, p.27066, 2015.

A. Piccin, W. G. Murphy, and O. P. Smith, Circulating microparticles: pathophysiology and clinical implications, Blood Reviews, vol.21, pp.157-171, 2007.

F. Ender, N. V. Bubnoff, F. Gieseler, and E. Vesicles, Subcellular Organelles With the Potential to Spread Cancer Resistance, Anticancer Res, vol.39, pp.3395-3404, 2019.

J. Skog, T. Würdinger, S. Van-rijn, D. H. Meijer, L. Gainche et al., Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers, Nature Cell Biology, vol.10, pp.1470-1476, 2008.

M. Osaki and F. Okada, Exosomes and Their Role in Cancer Progression, Yonago Acta Medica, vol.62, pp.182-190, 2019.

S. A. Bellingham, B. B. Guo, B. M. Coleman, and A. F. Hill, Exosomes: vehicles for the transfer of toxic proteins associated with neurodegenerative diseases?, Front Physiol, vol.3, p.124, 2012.

M. Mack, A. Kleinschmidt, H. Brühl, C. Klier, P. J. Nelson et al., Transfer of the chemokine receptor CCR5 between cells by membrane-derived microparticles: a mechanism for cellular human immunodeficiency virus 1 infection, Nat. Med, vol.6, pp.769-775, 2000.

J. I. Zwicker, Predictive value of tissue factor bearing microparticles in cancer associated thrombosis, Thrombosis Research, vol.125, pp.89-91, 2010.

F. A. Coumans, C. J. Doggen, G. Attard, J. S. Bono, and L. W. Terstappen, All circulating EpCAM+CK+CD45-objects predict overall survival in castrationresistant prostate cancer, Ann. Oncol, vol.21, pp.1851-1857, 2010.

M. Nawaz, G. Camussi, H. Valadi, I. Nazarenko, K. Ekström et al., The emerging role of extracellular vesicles as biomarkers for urogenital cancers, Nat Rev Urol, vol.11, pp.688-701, 2014.

S. A. Melo, L. B. Luecke, C. Kahlert, A. F. Fernandez, S. T. Gammon et al., Glypican-1 identifies cancer exosomes and detects early pancreatic cancer, Nature, vol.523, pp.177-182, 2015.

L. Console, M. Scalise, and C. Indiveri, Exosomes in inflammation and role as biomarkers, Clinica Chimica Acta, vol.488, pp.165-171, 2019.

S. El-andaloussi, I. Mäger, X. O. Breakefield, and M. J. Wood, Extracellular vesicles: biology and emerging therapeutic opportunities, Nature Reviews Drug Discovery, vol.12, pp.347-357, 2013.

B. György, M. E. Hung, X. O. Breakefield, and J. N. Leonard, Therapeutic Applications of Extracellular Vesicles: Clinical Promise and Open Questions, Annual Review of Pharmacology and Toxicology, vol.55, pp.439-464, 2015.

X. Zhuang, X. Xiang, W. Grizzle, D. Sun, S. Zhang et al., Treatment of brain inflammatory diseases by delivering exosome encapsulated anti-inflammatory drugs from the nasal region to the brain, Mol. Ther, vol.19, pp.1769-1779, 2011.

F. A. Coumans, A. R. Brisson, E. I. Buzas, F. Dignat-george, E. E. Drees et al., Methodological Guidelines to Study Extracellular Vesicles. Circulation Research, vol.120, pp.1632-1648, 2017.

D. E. Murphy, O. G. Jong, M. Brouwer, M. J. Wood, G. Lavieu et al., Extracellular vesicle-based therapeutics: natural versus engineered targeting and trafficking, Exp. Mol. Med, vol.51, p.32, 2019.

C. Théry, M. Ostrowski, and E. Segura, Membrane vesicles as conveyors of immune responses, Nature Reviews Immunology, vol.9, pp.581-593, 2009.

L. Margolis and Y. Sadovsky, The biology of extracellular vesicles: The known unknowns, PLOS Biology, vol.17, p.3000363, 2019.

J. Lötvall, A. F. Hill, F. Hochberg, E. I. Buzás, D. D. Vizio et al., Minimal experimental requirements for definition of extracellular vesicles and their functions: a position statement from the International Society for Extracellular Vesicles, Journal of Extracellular Vesicles, vol.3, p.26913, 2014.

E. G. Trams, C. J. Lauter, J. N. Salem, and U. Heine, Exfoliation of membrane ectoenzymes in the form of micro-vesicles, Biochimica et Biophysica Acta (BBA) -Biomembranes, vol.645, pp.63-70, 1981.

C. Harding, J. Heuser, and P. Stahl, Receptor-mediated endocytosis of transferrin and recycling of the transferrin receptor in rat reticulocytes, J. Cell Biol, vol.97, pp.329-339, 1983.

B. T. Pan, K. Teng, C. Wu, M. Adam, and R. M. Johnstone, Electron microscopic evidence for externalization of the transferrin receptor in vesicular form in sheep reticulocytes, J. Cell Biol, vol.101, pp.942-948, 1985.

T. Mercedes, K. Joanna, and T. Clotilde, Why the need and how to approach the functional diversity of extracellular vesicles, Philosophical Transactions of the Royal Society B: Biological Sciences, vol.373, p.20160479, 2018.

P. Wolf, The nature and significance of platelet products in human plasma, Br J Haematol, vol.13, pp.269-88, 1967.

V. R. Minciacchi, M. R. Freeman, and D. D. Vizio, Extracellular Vesicles in Cancer: Exosomes, Microvesicles and the Emerging Role of Large Oncosomes, Seminars in Cell & Developmental Biology, vol.40, pp.41-51, 2015.

D. K. Jeppesen, A. M. Fenix, J. L. Franklin, J. N. Higginbotham, Q. Zhang et al., Reassessment of Exosome Composition. Cell, vol.177, 2019.

E. Willms, C. Cabañas, I. Mäger, M. J. Wood, and P. Vader, Extracellular Vesicle Heterogeneity: Subpopulations, Isolation Techniques, and Diverse Functions in Cancer Progression, Front. Immunol, vol.9, 2018.

G. Raposo and W. Stoorvogel, Extracellular vesicles: Exosomes, microvesicles, and friends, J Cell Biol, vol.200, pp.373-383, 2013.

C. Théry, K. W. Witwer, E. Aikawa, M. J. Alcaraz, J. D. Anderson et al.,

I. Buzás, J. B. Byrd, G. Camussi, D. R. Carter, S. Caruso et al.,

C. Chang, S. Chen, L. Chen, A. R. Cheng, A. Chin et al.,

S. Kano, Y. Kaur, E. T. Kawamura, D. Keller, E. Khamari et al.,

V. Webber, A. M. Weber, D. J. Wehman, J. A. Weiss, S. Welsh et al., Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J Extracell Vesicles, vol.7, p.1535750, 2018.
URL : https://hal.archives-ouvertes.fr/hal-02323217

M. P. Zaborowski, L. Balaj, X. O. Breakefield, and C. P. Lai, Extracellular Vesicles: Composition, Biological Relevance, and Methods of Study, BioScience, vol.65, pp.783-797, 2015.

T. Vagner, C. Spinelli, V. R. Minciacchi, L. Balaj, M. Zandian et al., Large extracellular vesicles carry most of the tumour DNA circulating in prostate cancer patient plasma, Journal of Extracellular Vesicles, vol.7, p.1505403, 2018.

L. Balaj, R. Lessard, L. Dai, Y. Cho, S. L. Pomeroy et al., Tumour microvesicles contain retrotransposon elements and amplified oncogene sequences, Nature Communications, vol.2, p.180, 2011.

B. K. Thakur, H. Zhang, A. Becker, I. Matei, Y. Huang et al., Double-stranded DNA in exosomes: a novel biomarker in cancer detection, Cell Research, vol.24, pp.766-769, 2014.

E. Lázaro-ibáñez, A. Sanz-garcia, T. Visakorpi, C. Escobedo-lucea, P. Siljander et al., Different gDNA content in the subpopulations of prostate cancer extracellular vesicles: apoptotic bodies, microvesicles, and exosomes, Prostate, vol.74, pp.1379-1390, 2014.

T. H. Lee, S. Chennakrishnaiah, E. Audemard, L. Montermini, B. Meehan et al., Oncogenic ras-driven cancer cell vesiculation leads to emission of double-stranded DNA capable of interacting with target cells, Biochemical and Biophysical Research Communications, vol.451, pp.295-301, 2014.

C. Kahlert, S. A. Melo, A. Protopopov, J. Tang, S. Seth et al., Identification of Double-stranded Genomic DNA Spanning All Chromosomes with Mutated KRAS and p53 DNA in the Serum Exosomes of Patients with Pancreatic Cancer, J Biol Chem, vol.289, pp.3869-3875, 2014.

M. Guescini, S. Genedani, V. Stocchi, and L. F. Agnati, Astrocytes and Glioblastoma cells release exosomes carrying mtDNA, J Neural Transm, vol.117, p.1, 2009.

A. Németh, N. Orgovan, B. W. Sódar, X. Osteikoetxea, K. Pálóczi et al., Antibiotic-induced release of small extracellular vesicles (exosomes) with surface-associated DNA, Scientific Reports, vol.7, p.8202, 2017.

P. Sansone, C. Savini, I. Kurelac, Q. Chang, L. B. Amato et al., Packaging and transfer of mitochondrial DNA via exosomes regulate escape from dormancy in hormonal therapy-resistant breast cancer, vol.114, pp.9066-9075, 2017.

J. Cai, W. Guan, X. Tan, C. Chen, L. Li et al., SRY gene transferred by extracellular vesicles accelerates atherosclerosis by promotion of leucocyte adherence to endothelial cells, Clinical Science, vol.129, pp.259-269, 2015.

A. Waldenström, N. Gennebäck, U. Hellman, and G. Ronquist, Cardiomyocyte Microvesicles Contain DNA/RNA and Convey Biological Messages to Target Cells, PLOS ONE, vol.7, p.34653, 2012.

S. Fischer, K. Cornils, T. Speiseder, A. Badbaran, R. Reimer et al., Indication of Horizontal DNA Gene Transfer by Extracellular Vesicles, PLOS ONE, vol.11, p.163665, 2016.

G. V. Shelke, S. C. Jang, Y. Yin, C. Lässer, and J. Lötvall, Human mast cells release extracellular vesicle-associated DNA, Matters, vol.2, p.201602000034, 2016.

A. Takahashi, R. Okada, K. Nagao, Y. Kawamata, A. Hanyu et al., Exosomes maintain cellular homeostasis by excreting harmful DNA from cells, Nature Communications, vol.8, p.15287, 2017.

E. Dzierzak and S. Philipsen, Erythropoiesis: Development and Differentiation. Cold Spring Harbor Perspectives in Medicine, vol.3, pp.11601-011601, 2013.

A. R. Migliaccio, Erythroblast enucleation, Haematologica, vol.95, 1985.

M. Moras, S. D. Lefevre, and M. A. Ostuni, From Erythroblasts to Mature Red Blood Cells: Organelle Clearance in Mammals, Frontiers in Physiology, vol.8, 2017.

K. E. Mcgrath, Red cell island dances: switching hands, Blood, vol.123, pp.3847-3848, 2014.

A. E. Geddis, Megakaryopoiesis. Seminars in Hematology, vol.47, pp.212-219, 2010.

K. Tozawa, Y. Ono-uruga, Y. Matsubara, K. Tozawa, Y. Ono-uruga et al., Megakaryopoiesis. Clin Exp Thromb Hemost, vol.1, pp.54-58, 2014.

J. E. Italiano, P. Lecine, R. A. Shivdasani, and J. H. Hartwig, Blood Platelets Are Assembled Principally at the Ends of Proplatelet Processes Produced by Differentiated Megakaryocytes, J Cell Biol, vol.147, pp.1299-1312, 1999.

X. Sim, M. Poncz, P. Gadue, and D. L. French, Understanding platelet generation from megakaryocytes: implications for in vitro-derived platelets, Blood, vol.127, pp.1227-1233, 2016.

L. Raptis and H. A. Menard, Quantitation and characterization of plasma DNA in normals and patients with systemic lupus erythematosus, J Clin Invest, vol.66, pp.1391-1399, 1980.

Y. M. Lo, L. Y. Chan, K. W. Lo, S. F. Leung, J. Zhang et al., Quantitative analysis of cell-free Epstein-Barr virus DNA in plasma of patients with nasopharyngeal carcinoma, Cancer Res, vol.59, pp.1188-1191, 1999.

H. J. Yang, V. W. Liu, P. C. Tsang, A. M. Yip, K. F. Tam et al., Quantification of human papillomavirus DNA in the plasma of patients with cervical cancer, Int. J. Gynecol. Cancer, vol.14, pp.903-910, 2004.

D. Wichmann, M. Panning, T. Quack, S. Kramme, G. Burchard et al., Diagnosing Schistosomiasis by Detection of Cell-Free Parasite DNA in Human Plasma, PLOS Neglected Tropical Diseases, vol.3, p.422, 2009.

S. Spisák, N. Solymosi, P. Ittzés, A. Bodor, D. Kondor et al., Complete Genes May Pass from Food to Human Blood, PLOS ONE, vol.8, p.69805, 2013.

Y. Y. Lui, K. Chik, R. W. Chiu, C. Ho, C. W. Lam et al., Predominant Hematopoietic Origin of Cell-free DNA in Plasma and Serum after Sexmismatched Bone Marrow Transplantation, Clinical Chemistry, vol.48, pp.421-427, 2002.

S. Tug, S. Helmig, E. R. Deichmann, A. Schmeier-jürchott, E. Wagner et al., Exercise-induced increases in cell free DNA in human plasma originate predominantly from cells of the haematopoietic lineage, Exerc Immunol Rev, vol.21, pp.164-173, 2015.

Y. Dor and H. Cedar, Principles of DNA methylation and their implications for biology and medicine, Lancet, vol.392, pp.777-786, 2018.

A. F. Fernandez, Y. Assenov, J. I. Martin-subero, B. Balint, R. Siebert et al., A DNA methylation fingerprint of 1628 human samples, Genome Res, vol.22, pp.407-419, 2012.

A. Kundaje, J. Ernst, M. Bilenky, A. Yen, A. Heravi-moussavi et al.,

L. D. Jager, P. J. Farnham, S. J. Fisher, D. Haussler, S. J. Jones et al., Integrative analysis of 111 reference human epigenomes, Nature, vol.518, pp.317-330, 2015.

S. Moran, A. Martínez-cardús, S. Sayols, E. Musulén, C. Balañá et al., Epigenetic profiling to classify cancer of unknown primary: a multicentre, retrospective analysis, Lancet Oncol, vol.17, pp.1386-1395, 2016.

S. Guo, D. Diep, N. Plongthongkum, H. Fung, K. Zhang et al., Identification of methylation haplotype blocks aids in deconvolution of heterogeneous tissue samples and tumor tissue-of-origin mapping from plasma DNA, Nature Genetics, vol.49, p.635, 2017.

W. Tang, S. Wan, Z. Yang, A. E. Teschendorff, and Q. Zou, Tumor origin detection with tissue-specific miRNA and DNA methylation markers, Bioinformatics, vol.34, pp.398-406, 2018.

K. Sun, P. Jiang, K. C. Chan, J. Wong, Y. K. Cheng et al., Plasma DNA tissue mapping by genome-wide methylation sequencing for noninvasive prenatal, cancer, and transplantation assessments, PNAS, vol.112, pp.5503-5512, 2015.

J. Moss, J. Magenheim, D. Neiman, H. Zemmour, N. Loyfer et al., Comprehensive human cell-type methylation atlas reveals origins of circulating cell-free DNA in health and disease, Nature Communications, vol.9, 2018.

M. W. Snyder, M. Kircher, A. J. Hill, R. M. Daza, and J. Shendure, Cell-free DNA Comprises an In Vivo Nucleosome Footprint that Informs Its Tissues-Of-Origin, Cell, vol.164, pp.57-68, 2016.

R. Lehmann-werman, D. Neiman, H. Zemmour, J. Moss, J. Magenheim et al., Identification of tissue-specific cell death using methylation patterns of circulating DNA, vol.113, pp.1826-1834, 2016.

S. Holdenrieder, P. Stieber, H. Bodenmüller, M. Busch, J. Pawel et al., Circulating Nucleosomes in Serum. Annals of the New York Academy of Sciences, vol.945, pp.93-102, 2006.

H. R. Underhill, J. O. Kitzman, S. Hellwig, N. C. Welker, R. Daza et al., Fragment Length of Circulating Tumor DNA, PLOS Genetics, vol.12, p.1006162, 2016.

V. V. Vlassov, P. P. Laktionov, and E. Y. Rykova, Extracellular nucleic acids, BioEssays, vol.29, pp.654-667, 2007.

F. Mouliere, S. E. Messaoudi, D. Pang, A. Dritschilo, and A. R. Thierry, Multi-marker analysis of circulating cell-free DNA toward personalized medicine for colorectal cancer, Molecular Oncology, vol.8, pp.927-941, 2014.
URL : https://hal.archives-ouvertes.fr/inserm-01076572

F. Mouliere, B. Robert, E. Peyrotte, M. Rio, M. Ychou et al., High Fragmentation Characterizes Tumour-Derived Circulating DNA, PLoS ONE, vol.6, p.23418, 2011.
URL : https://hal.archives-ouvertes.fr/hal-02362667

K. C. Chan, Size Distributions of Maternal and Fetal DNA in Maternal Plasma, Clinical Chemistry, vol.50, pp.88-92, 2004.

G. Leszinski, J. Lehner, U. Gezer, and S. Holdenrieder, Increased DNA integrity in colorectal cancer, In Vivo, vol.28, pp.299-303, 2014.

S. Holdenrieder, A. Burges, O. Reich, F. W. Spelsberg, and P. Stieber, DNA integrity in plasma and serum of patients with malignant and benign diseases, Ann. N. Y. Acad. Sci, vol.1137, pp.162-170, 2008.

C. Sanchez, M. W. Snyder, R. Tanos, J. Shendure, and A. R. Thierry, New insights into structural features and optimal detection of circulating tumor DNA determined by single-strand DNA analysis, npj Genomic Medicine, vol.3, p.31, 2018.
URL : https://hal.archives-ouvertes.fr/hal-02292243

Y. Liu, A new perspective on Darwin's Pangenesis, vol.83, pp.141-149, 2008.

M. Stroun, C. C. Mathon, and J. Stroun, Alteration of hereditary traits in Solanum melongena induced by grafts with Solanum nigrum, Proceedings of the 11th International Congress of Genetics (la Haye, vol.1, p.218, 1963.

M. Stroun, C. Mathon, and J. Stroun, Modifications transmitted to the offspring, provoked by heterograft in Solanum melongena, Archives des Sciences, vol.16, pp.225-245, 1963.

P. B. Gahan and M. Stroun, Nucleic Acids and Molecular Biology, pp.167-189, 2010.

E. H. Szybalska and W. Szybalski, Genetics of human cess line. IV. DNA-mediated heritable transformation of a biochemical trait, Proc. Natl. Acad. Sci. U.S.A, vol.48, pp.2026-2034, 1962.

S. M. Gartler and O. R. Pavlovskis, Demonstration of celluar uptake of polymerized DNA in mammalian cell cultures, Biochem. Biophys. Res. Commun, vol.3, pp.127-131, 1960.

I. Mittra, N. K. Khare, G. V. Raghuram, R. Chaubal, F. Khambatti et al., Circulating nucleic acids damage DNA of healthy cells by integrating into their genomes, J. Biosci, vol.40, pp.91-111, 2015.

I. Mittra, K. Pal, N. Pancholi, A. Shaikh, B. Rane et al., Prevention of chemotherapy toxicity by agents that neutralize or degrade cell-free chromatin, Ann. Oncol, vol.28, pp.2119-2127, 2017.

P. Anker, D. Jachertz, M. Stroun, R. Brögger, C. Lederrey et al., Transfer of genetic information from T to B human lymphocytes during an immune response to herpes simplex virus

, C. R. Acad. Sci., D, Sci. Nat, vol.289, pp.217-220, 1979.

P. Anker, D. Jachertz, P. A. Maurice, and M. Stroun, Nude mice injected with DNA released by antigen stimulated human T lymphocytes produce specific antibodies expressing human characteristics, Cell Biochem. Funct, vol.2, pp.33-37, 1984.

D. C. García-olmo, C. Domínguez, M. García-arranz, P. Anker, M. Stroun et al., Cell-free nucleic acids circulating in the plasma of colorectal cancer patients induce the oncogenic transformation of susceptible cultured cells, Cancer Res, vol.70, pp.560-567, 2010.

D. Osti, M. D. Bene, G. Rappa, M. Santos, V. Matafora et al., Clinical Significance of Extracellular Vesicles in Plasma from Glioblastoma Patients, vol.25, pp.266-276, 2019.

L. Han, E. W. , .. Lam, and Y. Sun, Extracellular vesicles in the tumor microenvironment: old stories, but new tales. Molecular Cancer, vol.18, p.59, 2019.

M. Demers, S. L. Wong, K. Martinod, M. Gallant, J. E. Cabral et al., Priming of neutrophils toward NETosis promotes tumor growth, Oncoimmunology, vol.5, p.1134073, 2016.

A. Olsson and J. Cedervall, NETosis in Cancer -Platelet-Neutrophil Crosstalk Promotes Tumor-Associated Pathology, Front Immunol, vol.7, p.373, 2016.

J. Park, R. W. Wysocki, Z. Amoozgar, L. Maiorino, M. R. Fein et al., Cancer cells induce metastasis-supporting neutrophil extracellular DNA traps, Sci Transl Med, vol.8, pp.361-138, 2016.

J. Albrengues, M. A. Shields, D. Ng, C. G. Park, A. Ambrico et al., Neutrophil extracellular traps produced during inflammation awaken dormant cancer cells in mice, Science, vol.361, 2018.

L. Erpenbeck and M. P. Schön, Neutrophil extracellular traps: protagonists of cancer progression?, Oncogene, vol.36, pp.2483-2490, 2017.

A. West, Mitochondrial dysfunction as a trigger of innate immune responses and inflammation, Toxicology, vol.391, pp.54-63, 2017.

C. A. Janeway and R. Medzhitov, Innate Immune Recognition, Annual Review of Immunology, vol.20, pp.197-216, 2002.

O. Takeuchi and S. Akira, Pattern Recognition Receptors and Inflammation, vol.140, pp.805-820, 2010.

A. P. West, A. A. Koblansky, and S. Ghosh, Recognition and Signaling by Toll-Like Receptors, Annual Review of Cell and Developmental Biology, vol.22, pp.409-437, 2006.

D. Goubau, S. Deddouche, and C. Reis-e-sousa, Cytosolic Sensing of Viruses, Immunity, vol.38, pp.855-869, 2013.

L. Schaefer, Complexity of Danger: The Diverse Nature of Damage-associated Molecular Patterns, J. Biol. Chem, vol.289, pp.35237-35245, 2014.

G. Y. Chen and G. Nuñez, Sterile inflammation: sensing and reacting to damage, Nature Reviews Immunology, vol.10, pp.826-837, 2010.

K. L. Rock and H. Kono, The Inflammatory Response to Cell Death, Annual Review of Pathology: Mechanisms of Disease, vol.3, pp.99-126, 2008.

A. Roers, B. Hiller, and V. Hornung, Recognition of Endogenous Nucleic Acids by the Innate Immune System, Immunity, vol.44, pp.739-754, 2016.

D. S. Pisetsky, The origin and properties of extracellular DNA: From PAMP to DAMP, Clinical Immunology, vol.144, pp.32-40, 2012.

G. Marsman, S. Zeerleder, and B. M. Luken, Extracellular histones, cell-free DNA, or nucleosomes: differences in immunostimulation, Cell Death Dis, vol.7, p.2518, 2016.

G. N. Coritsidis, P. C. Beers, and P. M. Rumore, Glomerular uptake of nucleosomes: evidence for receptor-mediated mesangial cell binding, Kidney Int, vol.47, pp.1258-1265, 1995.

E. Ben-chetrit, E. H. Dunsky, S. Wollner, and D. Eilat, In vivo clearance and tissue uptake of an anti-DNA monoclonal antibody and its complexes with DNA, Clin. Exp. Immunol, vol.60, pp.159-168, 1985.

V. Urbonaviciute, B. G. Fürnrohr, S. Meister, L. Munoz, P. Heyder et al., Induction of inflammatory and immune responses by HMGB1-nucleosome complexes: implications for the pathogenesis of SLE, J. Exp. Med, vol.205, pp.3007-3018, 2008.

M. Napirei, H. Karsunky, B. Zevnik, H. Stephan, H. G. Mannherz et al., Features of systemic lupus erythematosus in Dnase1-deficient mice, Nat. Genet, vol.25, pp.177-181, 2000.

F. Martinez-valle, E. Balada, J. Ordi-ros, S. Bujan-rivas, A. Sellas-fernandez et al., DNase 1 activity in patients with systemic lupus erythematosus: relationship with epidemiological, clinical, immunological and therapeutical features, Lupus, vol.18, pp.418-423, 2009.

A. Kustanovich, R. Schwartz, T. Peretz, and A. Grinshpun, Life and death of circulating cell-free DNA, Cancer Biology & Therapy, vol.0, pp.1-11, 2019.

I. D. Vlaminck, H. A. Valantine, T. M. Snyder, C. Strehl, G. Cohen et al., Circulating Cell-Free DNA Enables Noninvasive Diagnosis of Heart Transplant Rejection, Science Translational Medicine, vol.6, pp.241-77, 2014.

A. Avriel, M. P. Wiessman, Y. Almog, Y. Perl, V. Novack et al., Admission Cell Free DNA Levels Predict 28-Day Mortality in Patients with Severe Sepsis in Intensive Care, PLOS ONE, vol.9, p.100514, 2014.

S. H. Nymo, T. Ueland, E. Askevold, C. P. Dahl, L. Gullestad et al., Circulating nucleosomes in chronic heart failure, International Journal of Cardiology, vol.203, pp.742-743, 2016.

Y. Dhondup, T. Ueland, C. P. Dahl, E. T. Askevold, Ø. Sandanger et al., Low Circulating Levels of Mitochondrial and High Levels of Nuclear DNA Predict Mortality in Chronic Heart Failure, J. Card. Fail, vol.22, pp.823-828, 2016.

E. R. Hammond, A. N. Shelling, and L. M. Cree, Nuclear and mitochondrial DNA in blastocoele fluid and embryo culture medium: evidence and potential clinical use, Hum. Reprod, vol.31, pp.1653-1661, 2016.

F. Mouliere and A. R. Thierry, 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, vol.12, pp.209-215, 2012.

A. Volckmar, H. Sültmann, A. Riediger, T. Fioretos, P. Schirmacher et al., A field guide for cancer diagnostics using cell-free DNA: From principles to practice and clinical applications, Genes, Chromosomes and Cancer, vol.57, pp.123-139, 2018.

S. Dawson, D. W. Tsui, M. Murtaza, H. Biggs, O. M. Rueda et al., Analysis of Circulating Tumor DNA to Monitor Metastatic Breast Cancer, 2013.

E. Heitzer, P. Ulz, and J. B. Geigl, Circulating Tumor DNA as a Liquid Biopsy for Cancer, Clinical Chemistry, vol.61, pp.112-123, 2015.

G. Sozzi, D. Conte, M. Leon, R. Cirincione, L. Roz et al., Quantification of Free Circulating DNA As a Diagnostic Marker in Lung Cancer, Journal of Clinical Oncology, vol.21, pp.3902-3908, 2003.

K. Kim, D. G. Shin, M. K. Park, S. H. Baik, T. H. Kim et al., Circulating cell-free DNA as a promising biomarker in patients with gastric cancer: diagnostic validity and significant reduction of cfDNA after surgical resection, Ann Surg Treat Res, vol.86, pp.136-142, 2014.

J. D. Cohen, L. Li, Y. Wang, C. Thoburn, B. Afsari et al.,

T. Molin, R. Wang, A. P. Roden, J. Klein, L. Ptak et al., Detection and localization of surgically resectable cancers with a multianalyte blood test, Science, vol.359, pp.926-930, 2018.

A. J. Bronkhorst, V. Ungerer, and S. Holdenrieder, The emerging role of cell-free DNA as a molecular marker for cancer management, Biomolecular Detection and Quantification, vol.17, p.100087, 2019.

G. Tian, X. Li, Y. Xie, F. Xu, D. Yu et al., The Early Diagnosis in Lung Cancer by the Detection of Circulating Tumor DNA, p.189340, 2017.

C. Bettegowda, M. Sausen, R. J. Leary, I. Kinde, Y. Wang et al., Detection of Circulating Tumor DNA in Early-and Late-Stage Human Malignancies, vol.6, pp.224-248, 2014.

J. C. Wan, C. Massie, J. Garcia-corbacho, F. Mouliere, J. D. Brenton et al., Liquid biopsies come of age: towards implementation of circulating tumour DNA, Nature Reviews Cancer, vol.17, pp.223-238, 2017.

K. C. Chan, J. K. Woo, A. King, B. C. Zee, W. K. Lam et al.,

S. Chiu, A. C. Leung, A. T. Van-hasselt, Y. M. Chan, and . Lo, Analysis of Plasma Epstein-Barr Virus DNA to Screen for Nasopharyngeal Cancer, New England Journal of Medicine, vol.377, pp.513-522, 2017.

F. Amant, M. Verheecke, I. Wlodarska, L. Dehaspe, P. Brady et al., Presymptomatic Identification of Cancers in Pregnant Women During Noninvasive Prenatal Testing, JAMA Oncol, vol.1, pp.814-819, 2015.

E. Gormally, P. Vineis, G. Matullo, F. Veglia, E. Caboux et al., TP53 and KRAS2 Mutations in Plasma DNA of Healthy Subjects and Subsequent Cancer Occurrence: A Prospective Study, vol.66, pp.6871-6876, 2006.

L. Mao, R. H. Hruban, J. O. Boyle, M. Tockman, and D. Sidransky, Detection of Oncogene Mutations in Sputum Precedes Diagnosis of Lung Cancer, Cancer Res, vol.54, pp.1634-1637, 1994.

C. A. Parkinson, D. Gale, A. M. Piskorz, H. Biggs, C. Hodgkin et al., Exploratory Analysis of TP53 Mutations in Circulating Tumour DNA as Biomarkers of Treatment Response for Patients with Relapsed High-Grade Serous Ovarian Carcinoma: A Retrospective Study, PLOS Medicine, vol.13, p.1002198, 2016.

A. R. Thierry, F. Mouliere, C. Gongora, J. Ollier, B. Robert et al., Origin and quantification of circulating DNA in mice with human colorectal cancer xenografts, Nucleic Acids Res, vol.38, pp.6159-6175, 2010.
URL : https://hal.archives-ouvertes.fr/hal-02362686

A. A. Kamat, F. Z. Bischoff, D. Dang, M. Baldwin, L. Y. Han et al., Circulating cell-free DNA: A novel biomarker for response to therapy in ovarian carcinoma, Cancer Biology & Therapy, vol.5, pp.1369-1374, 2006.

A. D. Nygaard, P. C. Holdgaard, K. G. Spindler, N. Pallisgaard, and A. Jakobsen, The correlation between cell-free DNA and tumour burden was estimated by PET/CT in patients with advanced NSCLC, British Journal of Cancer, vol.110, pp.363-368, 2014.

K. G. Spindler, A. L. Appelt, N. Pallisgaard, R. F. Andersen, I. Brandslund et al., Cell-free DNA in healthy individuals, noncancerous disease and strong prognostic value in colorectal cancer, International Journal of Cancer, vol.135, pp.2984-2991, 2014.

S. E. Messaoudi, F. Mouliere, S. D. Manoir, C. Bascoul-mollevi, B. Gillet et al., Circulating DNA as a Strong Multimarker Prognostic Tool for Metastatic Colorectal Cancer Patient Management Care, Clin Cancer Res, vol.22, pp.3067-3077, 2016.
URL : https://hal.archives-ouvertes.fr/hal-01826197

C. Oshiro, N. Kagara, Y. Naoi, M. Shimoda, A. Shimomura et al., PIK3CA mutations in serum DNA are predictive of recurrence in primary breast cancer patients, Breast Cancer Res. Treat, vol.150, pp.299-307, 2015.

R. Sirera, R. M. Bremnes, A. Cabrera, E. Jantus-lewintre, E. Sanmartín et al., Circulating DNA is a Useful Prognostic Factor in Patients with Advanced Non-small Cell Lung Cancer, Journal of Thoracic Oncology, vol.6, pp.286-290, 2011.

E. Sunami, M. Shinozaki, C. S. Higano, R. Wollman, T. B. Dorff et al., Multimarker circulating DNA assay for assessing blood of prostate cancer patients, Clin. Chem, vol.55, pp.559-567, 2009.

T. Lecomte, A. Berger, F. Zinzindohoué, S. Micard, B. Landi et al., Detection of free-circulating tumor-associated DNA in plasma of colorectal cancer patients and its association with prognosis -Lecomte -2002 -International Journal of Cancer -Wiley Online Library, Int. J. Cancer, vol.100, pp.542-548, 2002.

T. B. Hao, W. Shi, X. J. Shen, J. Qi, X. H. Wu et al., Circulating cell-free DNA in serum as a biomarker for diagnosis and prognostic prediction of colorectal cancer, Br. J. Cancer, vol.111, pp.1482-1489, 2014.

N. Umetani, A. E. Giuliano, S. H. Hiramatsu, F. Amersi, T. Nakagawa et al., Prediction of breast tumor progression by integrity of free circulating DNA in serum, J. Clin. Oncol, vol.24, pp.4270-4276, 2006.

D. Madhavan, M. Wallwiener, K. Bents, M. Zucknick, J. Nees et al., Plasma DNA integrity as a biomarker for primary and metastatic breast cancer and potential marker for early diagnosis, Breast Cancer Res. Treat, vol.146, pp.163-174, 2014.

K. C. Chan, S. Leung, S. Yeung, A. T. Chan, and Y. M. Lo, Persistent aberrations in circulating DNA integrity after radiotherapy are associated with poor prognosis in nasopharyngeal carcinoma patients, Clin. Cancer Res, vol.14, pp.4141-4145, 2008.

A. M. Aravanis, M. Lee, and R. D. Klausner, Next-Generation Sequencing of Circulating Tumor DNA for Early Cancer Detection, Cell, vol.168, pp.571-574, 2017.

J. Jin, X. Wu, J. Yin, M. Li, J. Shen et al., Identification of Genetic Mutations in Cancer: Challenge and Opportunity in the New Era of Targeted Therapy, Front. Oncol, vol.9, 2019.

Y. Chang, B. Tolani, X. Nie, X. Zhi, M. Hu et al., Review of the clinical applications and technological advances of circulating tumor DNA in cancer monitoring, Therapeutics and Clinical Risk Management, 2017.

R. A. Burrell, N. Mcgranahan, J. Bartek, and C. Swanton, The causes and consequences of genetic heterogeneity in cancer evolution, Nature, vol.501, pp.338-345, 2013.

K. H. Allison and G. W. Sledge, Heterogeneity and Cancer, vol.28, pp.772-778, 2014.

M. Gerlinger, A. J. Rowan, S. Horswell, J. Larkin, D. Endesfelder et al., Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing, New England Journal of Medicine, vol.366, pp.883-892, 2012.

L. A. Diaz and A. Bardelli, Liquid Biopsies: Genotyping Circulating Tumor DNA, JCO, vol.32, pp.579-586, 2014.

A. R. Thierry, F. Mouliere, S. E. Messaoudi, C. Mollevi, E. Lopez-crapez et al., Clinical validation of the detection of KRAS and BRAF mutations from circulating tumor DNA, Nature Medicine, vol.20, pp.430-435, 2014.
URL : https://hal.archives-ouvertes.fr/hal-02362372

Y. Li, H. Xu, S. Su, J. Ye, J. Chen et al., Clinical validation of a highly sensitive assay to detect EGFR mutations in plasma cell-free DNA from patients with advanced lung adenocarcinoma, PLOS ONE, vol.12, p.183331, 2017.

K. L. Aung, E. Donald, G. Ellison, S. Bujac, L. Fletcher et al., Analytical Validation of BRAF Mutation Testing from Circulating Free DNA Using the Amplification Refractory Mutation Testing System, The Journal of Molecular Diagnostics, vol.16, pp.343-349, 2014.

O. A. Zill, C. Greene, D. Sebisanovic, L. M. Siew, J. Leng et al., Cell-Free DNA Next-Generation Sequencing in Pancreatobiliary Carcinomas, Cancer Discov, vol.5, pp.1040-1048, 2015.

M. J. Higgins, D. Jelovac, E. Barnathan, B. Blair, S. Slater et al.,

B. H. Wolff and . Park, Detection of tumor PIK3CA status in metastatic breast cancer using peripheral blood, Clin. Cancer Res, vol.18, pp.3462-3469, 2012.

A. W. Wyatt, M. Annala, R. Aggarwal, K. Beja, F. Feng et al., Concordance of Circulating Tumor DNA and Matched Metastatic Tissue Biopsy in Prostate Cancer, J. Natl. Cancer Inst, vol.109, 2017.

S. Misale, F. D. Nicolantonio, A. Sartore-bianchi, S. Siena, and A. Bardelli, Resistance to Anti-EGFR Therapy in Colorectal Cancer: From Heterogeneity to Convergent Evolution, Cancer Discov, vol.4, pp.1269-1280, 2014.

A. Kulkarni, H. Al-hraishawi, S. Simhadri, K. M. Hirshfield, S. Chen et al., BRAF Fusion as a Novel Mechanism of Acquired Resistance to Vemurafenib in BRAFV600E Mutant Melanoma, Clin. Cancer Res, vol.23, pp.5631-5638, 2017.

K. Tanaka, K. Nosaki, K. Otsubo, K. Azuma, S. Sakata et al., Acquisition of the T790M resistance mutation during afatinib treatment in EGFR tyrosine kinase inhibitor-naïve patients with non-small cell lung cancer harboring EGFR mutations, Oncotarget, vol.8, pp.68123-68130, 2017.

M. Schreuer, G. Meersseman, S. V. Herrewegen, Y. Jansen, I. Chevolet et al., Quantitative assessment of BRAF V600 mutant circulating cell-free tumor DNA as a tool for therapeutic monitoring in metastatic melanoma patients treated with BRAF/MEK inhibitors, Journal of Translational Medicine, vol.14, p.95, 2016.

H. Bai, Z. Wang, K. Chen, J. Zhao, J. J. Lee et al., Influence of Chemotherapy on EGFR Mutation Status Among Patients With Non-Small-Cell Lung Cancer, JCO, vol.30, pp.3077-3083, 2012.

J. Tie, I. Kinde, Y. Wang, H. L. Wong, J. Roebert et al., Circulating tumor DNA as an early marker of therapeutic response in patients with metastatic colorectal cancer, Ann Oncol, vol.26, pp.1715-1722, 2015.

L. Cabel, F. Riva, V. Servois, A. Livartowski, C. Daniel et al., Circulating tumor DNA changes for early monitoring of anti-PD1 immunotherapy: a proof-of-concept study, Ann Oncol, vol.28, 1996.

L. B. Ahlborn, I. V. Tuxen, F. Mouliere, S. Kinalis, A. Y. Schmidt et al., Circulating tumor DNA as a marker of treatment response in BRAF V600E mutated non-melanoma solid tumors, Oncotarget, vol.9, pp.32570-32579, 2018.

S. Kruger, V. Heinemann, C. Ross, F. Diehl, D. Nagel et al., Repeated mutKRAS ctDNA measurements represent a novel and promising tool for early response prediction and therapy monitoring in advanced pancreatic cancer, Ann Oncol, vol.29, pp.2348-2355, 2018.

C. Demuth, A. Winther-larsen, A. T. Madsen, P. Meldgaard, and B. S. Sorensen, A method for treatment monitoring using circulating tumour DNA in cancer patients without targetable mutations, Oncotarget, vol.9, pp.31066-31076, 2018.

K. G. Spindler, N. Pallisgaard, I. Vogelius, and A. Jakobsen, Quantitative Cell-Free DNA, KRAS, and BRAF Mutations in Plasma from Patients with Metastatic Colorectal Cancer during Treatment with Cetuximab and Irinotecan, Clin Cancer Res, vol.18, pp.1177-1185, 2012.

K. Birkenkamp-demtröder, E. Christensen, I. Nordentoft, M. Knudsen, A. Taber et al., Monitoring Treatment Response and Metastatic Relapse in Advanced Bladder Cancer by Liquid Biopsy Analysis, European Urology, vol.73, pp.535-540, 2018.

L. A. Diaz, R. Williams, J. Wu, I. Kinde, J. R. Hecht et al., The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers, Nature, vol.486, pp.537-540, 2012.

A. R. Thierry, B. Pastor, Z. Jiang, A. D. Katsiampoura, C. Parseghian et al., Circulating DNA demonstrates convergent evolution and common resistance mechanisms during treatment of colorectal cancer, Clin Cancer Res, vol.23, pp.4578-4591, 2017.
URL : https://hal.archives-ouvertes.fr/hal-02292236

M. Murtaza, S. Dawson, D. W. Tsui, D. Gale, T. Forshew et al., Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA, Nature, vol.497, pp.108-112, 2013.

F. Bidard, J. Madic, P. Mariani, S. Piperno-neumann, A. Rampanou et al., Detection rate and prognostic value of circulating tumor cells and circulating tumor DNA in metastatic uveal melanoma, Int. J. Cancer, vol.134, pp.1207-1213, 2014.

T. Reinert, L. V. Schøler, R. Thomsen, H. Tobiasen, S. Vang et al., Analysis of circulating tumour DNA to monitor disease burden following colorectal cancer surgery, Gut, vol.65, pp.625-634, 2016.

M. Frattini, G. Gallino, S. Signoroni, D. Balestra, L. Lusa et al., Quantitative and qualitative characterization of plasma DNA identifies primary and recurrent colorectal cancer, Cancer Lett, vol.263, pp.170-181, 2008.

N. Guo, F. Lou, Y. Ma, J. Li, B. Yang et al., Circulating tumor DNA detection in lung cancer patients before and after surgery, Sci Rep, vol.6, 2016.

F. Diehl, K. Schmidt, M. A. Choti, K. Romans, S. Goodman et al., Circulating mutant DNA to assess tumor dynamics, Nat. Med, vol.14, pp.985-990, 2008.

A. A. Chaudhuri, J. J. Chabon, A. F. Lovejoy, A. M. Newman, H. Stehr et al., Early Detection of Molecular Residual Disease in Localized Lung Cancer by Circulating Tumor DNA Profiling, Cancer Discov, vol.7, pp.1394-1403, 2017.

M. W. Gray, Mitochondrial Evolution, Cold Spring Harb Perspect Biol, vol.4, 2012.

W. Schwartz and L. Margulis, Origin of Eukaryotic Cells. Evidence and Research Implications for a Theory of the Origin and Evolution of Microbial, Plant, and Animal Cells on the Precambrian Earth. Zeitschrift für allgemeine Mikrobiologie, vol.13, pp.186-186, 1973.

J. R. Friedman and J. Nunnari, Mitochondrial form and function, Nature, vol.505, pp.335-343, 2014.

S. W. Tait and D. R. Green, Mitochondria and cell signalling, Journal of Cell Science, vol.125, pp.807-815, 2012.

J. G. Mccarron, C. Wilson, M. E. Sandison, M. L. Olson, J. M. Girkin et al., From Structure to Function: Mitochondrial Morphology, Motion and Shaping in Vascular Smooth Muscle, Journal of Vascular Research, vol.50, pp.357-371, 2013.

J. Nunnari and A. Suomalainen, Mitochondria: In Sickness and in Health, Cell, vol.148, pp.1145-1159, 2012.

A. Rongvaux, Innate immunity and tolerance toward mitochondria, Mitochondrion, vol.41, pp.14-20, 2018.

R. H. Houtkooper and F. M. Vaz, Cardiolipin, the heart of mitochondrial metabolism, Cell. Mol. Life Sci, vol.65, pp.2493-2506, 2008.

D. K. Aanen, J. N. Spelbrink, and M. Beekman, What cost mitochondria? The maintenance of functional mitochondrial DNA within and across generations, Philos Trans R Soc Lond B Biol Sci, vol.369, 2014.

A. Lièvre and P. Laurent-puig, Mutations de l'ADN mitochondrial et cancer colorectal, Gastroentérologie Clinique et Biologique, vol.29, pp.33-40, 2005.

J. Taanman, The mitochondrial genome: structure, transcription, translation and replication, Biochimica et Biophysica Acta (BBA) -Bioenergetics, pp.103-123, 1410.

R. W. Taylor and D. M. Turnbull, Mitochondrial DNA mutations in human disease, Nature Reviews Genetics, vol.6, pp.389-402, 2005.

H. Sharma, A. Singh, C. Sharma, S. K. Jain, and N. Singh, Mutations in the mitochondrial DNA D-loop region are frequent in cervical cancer, Cancer Cell Int, vol.5, p.34, 2005.

C. Kukat, C. A. Wurm, H. Spahr, M. Falkenberg, N. Larsson et al., Superresolution microscopy reveals that mammalian mitochondrial nucleoids have a uniform size and frequently contain a single copy of mtDNA, Proceedings of the National Academy of Sciences, vol.108, pp.13534-13539, 2011.

F. Legros, F. Malka, P. Frachon, A. Lombès, and M. Rojo, Organization and dynamics of human mitochondrial DNA, Journal of Cell Science, vol.117, pp.2653-2662, 2004.

X. J. Chen and R. A. Butow, The organization and inheritance of the mitochondrial genome, Nature Reviews Genetics, vol.6, p.815, 2005.

Y. Wang and D. F. Bogenhagen, Human Mitochondrial DNA Nucleoids Are Linked to Protein Folding Machinery and Metabolic Enzymes at the Mitochondrial Inner Membrane, J. Biol. Chem, vol.281, pp.25791-25802, 2006.

T. I. Alam, Human mitochondrial DNA is packaged with TFAM, Nucleic Acids Research, vol.31, pp.1640-1645, 2003.

I. J. Holt, A. E. Harding, and J. A. Morgan-hughes, Deletions of muscle mitochondrial DNA in patients with mitochondrial myopathies, Nature, vol.331, p.717, 1988.

D. C. Wallace, G. Singh, M. T. Lott, J. A. Hodge, T. G. Schurr et al., Mitochondrial DNA mutation associated with Leber's hereditary optic neuropathy, Science, vol.242, pp.1427-1430, 1988.

E. A. Schon, S. Dimauro, and M. Hirano, Human mitochondrial DNA: roles of inherited and somatic mutations, Nat. Rev. Genet, vol.13, pp.878-890, 2012.

H. A. Tuppen, E. L. Blakely, D. M. Turnbull, and R. W. Taylor, Mitochondrial DNA mutations and human disease, Biochimica et Biophysica Acta (BBA) -Bioenergetics, vol.1797, pp.113-128, 2010.

E. Ylikallio and A. Suomalainen, Mechanisms of mitochondrial diseases, Ann. Med, vol.44, pp.41-59, 2012.

R. E. Giles, H. Blanc, H. M. Cann, and D. C. Wallace, Maternal inheritance of human mitochondrial DNA, Proc. Natl. Acad. Sci. U.S.A, vol.77, pp.6715-6719, 1980.

P. Yu-wai-man, P. G. Griffiths, D. T. Brown, N. Howell, D. M. Turnbull et al., The epidemiology of Leber hereditary optic neuropathy in the North East of England, Am. J. Hum. Genet, vol.72, pp.333-339, 2003.

T. R. Prezant, J. V. Agapian, M. C. Bohlman, X. Bu, S. Oztas et al., Mitochondrial ribosomal RNA mutation associated with both antibiotic-induced and non-syndromic deafness, Nat. Genet, vol.4, pp.289-294, 1993.

D. T. Brown, D. C. Samuels, E. M. Michael, D. M. Turnbull, and P. F. Chinnery, Random Genetic Drift Determines the Level of Mutant mtDNA in Human Primary Oocytes, Am J Hum Genet, vol.68, pp.533-536, 2001.

C. B. Park and N. Larsson, Mitochondrial DNA mutations in disease and aging, J Cell Biol, vol.193, pp.809-818, 2011.

D. Harman, Free radical theory of aging, Mutat. Res, vol.275, pp.257-266, 1992.

L. C. Greaves, A. K. Reeve, R. W. Taylor, and D. M. Turnbull, Mitochondrial DNA and disease, J. Pathol, vol.226, pp.274-286, 2012.

D. C. Wallace, A mitochondrial paradigm for degenerative diseases and ageing, Novartis Found. Symp, vol.235, pp.263-266, 2001.

W. C. Copeland, J. T. Wachsman, F. M. Johnson, and J. S. Penta, Mitochondrial DNA Alterations in Cancer, Cancer Investigation, vol.20, pp.557-569, 2002.

R. W. Chiu, Quantitative Analysis of Circulating Mitochondrial DNA in Plasma, Clinical Chemistry, vol.49, pp.719-726, 2003.

S. Zhong, M. C. Ng, Y. M. Lo, J. C. Chan, and P. J. Johnson, Presence of mitochondrial tRNA Leu(UUR) A to G 3243 mutation in DNA extracted from serum and plasma of patients with type 2 diabetes mellitus, Journal of Clinical Pathology, vol.53, pp.466-469, 2000.

N. Mehra, M. Penning, J. Maas, N. Van-daal, R. H. Giles et al., Circulating Mitochondrial Nucleic Acids Have Prognostic Value for Survival in Patients with Advanced Prostate Cancer, Clin Cancer Res, vol.13, pp.421-426, 2007.

R. Mair, F. Mouliere, C. G. Smith, D. Chandrananda, D. Gale et al., Measurement of Plasma Cell-Free Mitochondrial Tumor DNA Improves Detection of Glioblastoma in Patient-Derived Orthotopic Xenograft Models, Cancer Res, vol.79, pp.220-230, 2019.

E. H. Mahmoud, A. Fawzy, O. K. Ahmad, and A. M. Ali, Plasma Circulating Cell-free Nuclear and Mitochondrial DNA as Potential Biomarkers in the Peripheral Blood of Breast Cancer Patients, Asian Pacific Journal of Cancer Prevention, vol.16, pp.8299-8305, 2016.

J. Fernandes, V. Michel, M. Camorlinga-ponce, A. Gomez, C. Maldonado et al., Circulating Mitochondrial DNA Level, a Noninvasive Biomarker for the Early Detection of Gastric Cancer, Cancer Epidemiol Biomarkers Prev, vol.23, pp.2430-2438, 2014.
URL : https://hal.archives-ouvertes.fr/hal-01652002

J. Ellinger, P. Albers, S. C. Müller, A. V. Ruecker, and P. J. Bastian, Circulating mitochondrial DNA in the serum of patients with testicular germ cell cancer as a novel noninvasive diagnostic biomarker, BJU International, vol.104, pp.48-52, 2009.

J. Ellinger, D. C. Müller, S. C. Müller, S. Hauser, L. C. Heukamp et al., Circulating mitochondrial DNA in serum: A universal diagnostic biomarker for patients with urological malignancies. Urologic Oncology: Seminars and Original Investigations, vol.30, pp.509-515, 2012.

W. Jiang, B. Masayesva, M. Zahurak, A. L. Carvalho, E. Rosenbaum et al., Increased Mitochondrial DNA Content in Saliva Associated with Head and Neck Cancer, Clin Cancer Res, vol.11, pp.2486-2491, 2005.

, Cell-free Circulating Mitochondrial DNA in the Serum: A Potential Non-invasive Biomarker for Ewing's Sarcoma

R. Meddeb, Z. Amir-dache, S. Thezenas, A. Otandault, R. Tanos et al., Quantifying circulating cell-free DNA in humans, Scientific Reports, vol.9, p.5220, 2019.
URL : https://hal.archives-ouvertes.fr/hal-02327317

J. Chen, L. Zhang, X. Yu, H. Zhou, Y. Luo et al., Clinical application of plasma mitochondrial DNA content in patients with lung cancer, Oncology Letters, vol.16, pp.7074-7081, 2018.

P. Xia, H. An, C. Dang, R. Radpour, C. Kohler et al., Decreased mitochondrial DNA content in blood samples of patients with stage I breast cancer, BMC Cancer, vol.9, 2009.

C. Huang, Y. Chen, C. Wu, C. Tsai, Y. Lee et al., Circulating free mitochondrial DNA concentration and its association with erlotinib treatment in patients with adenocarcinoma of the lung, Oncol Lett, vol.7, pp.2180-2184, 2014.

J. Ellinger, S. C. Müller, N. Wernert, A. Ruecker, and P. J. Bastian, Mitochondrial DNA in serum of patients with prostate cancer: a predictor of biochemical recurrence after prostatectomy, BJU Int, vol.102, pp.628-632, 2008.

M. Patrushev, V. Kasymov, V. Patrusheva, T. Ushakova, V. Gogvadze et al., Mitochondrial permeability transition triggers the release of mtDNA fragments, Cell. Mol. Life Sci, vol.61, pp.3100-3103, 2004.

R. J. Youle and D. P. Narendra, Mechanisms of mitophagy, Nature Reviews Molecular Cell Biology, vol.12, pp.9-14, 2011.

T. Oka, S. Hikoso, O. Yamaguchi, M. Taneike, T. Takeda et al., Mitochondrial DNA that escapes from autophagy causes inflammation and heart failure, Nature, vol.485, pp.251-255, 2012.

H. Nakahirakiichi and C. M. , The Roles of Mitochondrial Damage-Associated Molecular Patterns in Diseases, Antioxidants & Redox Signaling, 2015.

A. Kaczmarek, P. Vandenabeele, and D. V. Krysko, Necroptosis: The Release of Damage-Associated Molecular Patterns and Its Physiological Relevance, Immunity, vol.38, pp.209-223, 2013.

A. Maeda and B. Fadeel, Mitochondria released by cells undergoing TNF-?-induced necroptosis act as danger signals, Cell Death & Disease, vol.5, pp.1312-1312, 2014.

L. H. Boudreau, A. Duchez, N. Cloutier, D. Soulet, N. Martin et al., Platelets release mitochondria serving as substrate for bactericidal group IIA-secreted phospholipase A2 to promote inflammation, Blood, vol.124, pp.2173-2183, 2014.

B. Ingelsson, D. Söderberg, T. Strid, A. Söderberg, A. Bergh et al., Lymphocytes eject interferogenic mitochondrial DNA webs in response to CpG and non-CpG oligodeoxynucleotides of class C, PNAS, vol.115, pp.478-487, 2018.

P. Jiang, C. W. Chan, K. C. Chan, S. H. Cheng, J. Wong et al., Lengthening and shortening of plasma DNA in hepatocellular carcinoma patients, Proceedings of the National Academy of Sciences, vol.112, pp.1317-1325, 2015.

R. Zhang, K. Nakahira, X. Guo, A. M. Choi, and Z. Gu, Very Short Mitochondrial DNA Fragments and Heteroplasmy in Human Plasma, Scientific Reports, vol.6, p.36097, 2016.

P. Burnham, M. S. Kim, S. Agbor-enoh, H. Luikart, H. A. Valantine et al., Single-stranded DNA library preparation uncovers the origin and diversity of ultrashort cell-free DNA in plasma, Scientific Reports, vol.6, 2016.

C. Newell, S. Hume, S. C. Greenway, L. Podemski, J. Shearer et al., Plasmaderived cell-free mitochondrial DNA: A novel non-invasive methodology to identify mitochondrial DNA haplogroups in humans, Mol. Genet. Metab, vol.125, pp.332-337, 2018.

M. Li, R. Schröder, S. Ni, B. Madea, and M. Stoneking, Extensive tissue-related and allelerelated mtDNA heteroplasmy suggests positive selection for somatic mutations, Proc Natl Acad Sci U S A, vol.112, pp.2491-2496, 2015.

Q. Zhang, K. Itagaki, and C. J. Hauser, Mitochondrial DNA is released by shock and activates neutrophils via p38 MAP kinase, Shock, vol.34, pp.55-59, 2010.

C. G. Mccarthy, C. F. Wenceslau, S. Goulopoulou, S. Ogbi, B. Baban et al., Circulating mitochondrial DNA and Toll-like receptor 9 are associated with vascular dysfunction in spontaneously hypertensive rats, Cardiovasc. Res, vol.107, pp.119-130, 2015.

K. Zaremba-niedzwiedzka, E. F. Caceres, J. H. Saw, D. Bäckström, L. Juzokaite et al., Asgard archaea illuminate the origin of eukaryotic cellular complexity, Nature, vol.541, pp.353-358, 2017.

A. Caicedo, P. M. Aponte, F. Cabrera, C. Hidalgo, and M. Khoury, Artificial Mitochondria Transfer: Current Challenges, Advances, and Future Applications, Stem Cells International, 2017.

T. Kitani, D. Kami, T. Kawasaki, M. Nakata, S. Matoba et al., Direct Human Mitochondrial Transfer: A Novel Concept Based on the Endosymbiotic Theory. Transplantation Proceedings, vol.46, pp.1233-1236, 2014.

J. L. Spees, S. D. Olson, M. J. Whitney, and D. J. Prockop, Mitochondrial transfer between cells can rescue aerobic respiration, Proc. Natl. Acad. Sci. U.S.A, vol.103, pp.1283-1288, 2006.

M. N. Islam, S. R. Das, M. T. Emin, M. Wei, L. Sun et al., Mitochondrial transfer from bonemarrow-derived stromal cells to pulmonary alveoli protects against acute lung injury, Nat. Med, vol.18, pp.759-765, 2012.

K. Hayakawa, E. Esposito, X. Wang, Y. Terasaki, Y. Liu et al., Transfer of mitochondria from astrocytes to neurons after stroke, Nature, vol.535, pp.551-555, 2016.

T. Ahmad, S. Mukherjee, B. Pattnaik, M. Kumar, S. Singh et al., Miro1 regulates intercellular mitochondrial transport & enhances mesenchymal stem cell rescue efficacy, EMBO J, vol.33, pp.994-1010, 2014.

C. A. Pacak, J. M. Preble, H. Kondo, P. Seibel, S. Levitsky et al., Actin-dependent mitochondrial internalization in cardiomyocytes: evidence for rescue of mitochondrial function, Biology Open, vol.4, pp.622-626, 2015.

M. V. Jackson, T. J. Morrison, D. F. Doherty, D. F. Mcauley, M. A. Matthay et al., Mitochondrial Transfer via Tunneling Nanotubes is an Important Mechanism by Which Mesenchymal Stem Cells Enhance Macrophage Phagocytosis in the In Vitro and In Vivo Models of ARDS, Stem Cells, vol.34, pp.2210-2223, 2016.

D. Torralba, F. Baixauli, and F. Sánchez-madrid, Mitochondria Know No Boundaries: Mechanisms and Functions of Intercellular Mitochondrial Transfer, vol.4, p.107, 2016.

M. A. Clark and J. W. Shay, Mitochondrial transformation of mammalian cells, NATURE, vol.295, pp.605-607, 1982.

M. P. King and G. Attardi, Injection of mitochondria into human cells leads to a rapid replacement of the endogenous mitochondrial DNA, Cell, vol.52, pp.811-819, 1988.

M. P. King and G. Attardi, Human cells lacking mtDNA: repopulation with exogenous mitochondria by complementation, Science, vol.246, pp.500-503, 1989.

A. Caicedo, V. Fritz, J. Brondello, M. Ayala, I. Dennemont et al., MitoCeption as a new tool to assess the effects of mesenchymal stem/stromal cell mitochondria on cancer cell metabolism and function, Scientific Reports, vol.5, 2015.
URL : https://hal.archives-ouvertes.fr/hal-01834600

S. E. Messaoudi, F. Rolet, F. Mouliere, and A. R. Thierry, Circulating cell free DNA: Preanalytical considerations, Clinica Chimica Acta, vol.424, pp.222-230, 2013.

R. Meddeb, E. Pisareva, and A. R. Thierry, Guidelines for the Preanalytical Conditions for Analyzing Circulating Cell-Free DNA, Clin. Chem, vol.65, pp.623-633, 2019.
URL : https://hal.archives-ouvertes.fr/hal-02421322

R. A. Haraszti, M. Didiot, E. Sapp, J. Leszyk, S. A. Shaffer et al., High-resolution proteomic and lipidomic analysis of exosomes and microvesicles from different cell sources, Journal of Extracellular Vesicles, vol.5, p.32570, 2016.

M. Durcin, A. Fleury, E. Taillebois, G. Hilairet, Z. Krupova et al., Characterisation of adipocyte-derived extracellular vesicle subtypes identifies distinct protein and lipid signatures for large and small extracellular vesicles, Journal of Extracellular Vesicles, vol.6, p.1305677, 2017.
URL : https://hal.archives-ouvertes.fr/hal-01606680

J. Kowal, G. Arras, M. Colombo, M. Jouve, J. P. Morath et al., Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes, PNAS, vol.113, pp.968-977, 2016.
URL : https://hal.archives-ouvertes.fr/inserm-02450678

S. Keerthikumar, L. Gangoda, M. Liem, P. Fonseka, I. Atukorala et al., Proteogenomic analysis reveals exosomes are more oncogenic than ectosomes, Oncotarget, vol.6, pp.15375-15396, 2015.

V. R. Minciacchi, S. You, C. Spinelli, S. Morley, M. Zandian et al.,

E. Kim, E. T. Hosseini-beheshti, M. Guns, Y. S. Gleave, S. Gho et al., Large oncosomes contain distinct protein cargo and represent a separate functional class of tumor-derived extracellular vesicles, Oncotarget, vol.6, pp.11327-11341, 2015.

S. Dames, L. Chou, Y. Xiao, T. Wayman, J. Stocks et al., The Development of Next-Generation Sequencing Assays for the Mitochondrial Genome and 108 Nuclear Genes Associated with Mitochondrial Disorders, The Journal of Molecular Diagnostics, vol.15, pp.526-534, 2013.

R. Lacroix, C. Judicone, P. Poncelet, S. Robert, L. Arnaud et al., Impact of pre-analytical parameters on the measurement of circulating microparticles: towards standardization of protocol, Journal of Thrombosis and Haemostasis, vol.10, pp.437-446, 2012.

C. Rigothier, R. Daculsi, S. Lepreux, P. Auguste, J. Villeneuve et al., CD154 Induces Matrix Metalloproteinase-9 Secretion in Human Podocytes, vol.117, pp.2737-2747, 2016.
URL : https://hal.archives-ouvertes.fr/inserm-02870968

E. Lázaro-ibáñez, C. Lässer, G. V. Shelke, R. Crescitelli, S. C. Jang et al., DNA analysis of low-and high-density fractions defines heterogeneous subpopulations of small extracellular vesicles based on their DNA cargo and topology, Journal of Extracellular Vesicles, vol.8, p.1656993, 2019.

C. Frezza, S. Cipolat, and L. Scorrano, Organelle isolation: functional mitochondria from mouse liver, muscle and cultured filroblasts, Nature Protocols, vol.2, pp.287-295, 2007.

S. Cointe, C. Judicone, S. Robert, M. J. Mooberry, P. Poncelet et al., Standardization of microparticle enumeration across different flow cytometry platforms: results of a multicenter collaborative workshop, J Thromb Haemost, vol.15, pp.187-193, 2017.
URL : https://hal.archives-ouvertes.fr/hal-01459831

G. Marcoux, A. Duchez, N. Cloutier, P. Provost, P. A. Nigrovic et al., Revealing the diversity of extracellular vesicles using high-dimensional flow cytometry analyses, Scientific Reports, vol.6, p.35928, 2016.

S. Pickles, N. Arbour, C. Vande, and . Velde, Immunodetection of Outer Membrane Proteins by Flow Cytometry of Isolated Mitochondria, J Vis Exp, 2014.

N. Arraud, C. Gounou, R. Linares, and A. R. Brisson, A simple flow cytometry method improves the detection of phosphatidylserine-exposing extracellular vesicles, Journal of Thrombosis and Haemostasis, vol.13, pp.237-247, 2015.

S. Mastoridis, G. M. Bertolino, G. Whitehouse, F. Dazzi, A. Sanchez-fueyo et al., Multiparametric Analysis of Circulating Exosomes and Other Small Extracellular Vesicles by, Advanced Imaging Flow Cytometry. Front. Immunol, vol.9, 2018.

T. Kobayashi, S. Kuroda, M. Tada, K. Houkin, Y. Iwasaki et al., Calcium-induced mitochondrial swelling and cytochrome c release in the brain: its biochemical characteristics and implication in ischemic neuronal injury, Brain Research, vol.960, pp.62-70, 2003.

J. J. Lemasters, T. P. Theruvath, Z. Zhong, and A. Nieminen, Mitochondrial Calcium and the Permeability Transition in Cell Death, Biochim Biophys Acta, vol.1787, pp.1395-1401, 2009.

P. Florian, A. Taras, R. Ulrike, O. Georg, R. Manfred et al., Mitochondria Are a Subset of Extracellular Vesicles Released by Activated Monocytes and Induce Type I IFN and TNF Responses in Endothelial Cells, Circulation Research, vol.125, pp.43-52, 2019.

A. Saraste and K. Pulkki, Morphologic and biochemical hallmarks of apoptosis, Cardiovasc Res, vol.45, pp.528-537, 2000.

M. Zhu, A. S. Barbas, L. Lin, U. Scheuermann, M. Bishawi et al., Mitochondria Released by Apoptotic Cell Death Initiate Innate Immune Responses, ImmunoHorizons, vol.2, pp.384-397, 2018.

H. Wajant, The Fas Signaling Pathway: More Than a Paradigm, Science, vol.296, pp.1635-1636, 2002.

K. Mcarthur, L. W. Whitehead, J. M. Heddleston, L. Li, B. S. Padman et al.,

L. Saunders, C. Sugiana, R. Lessene, L. D. Osellame, T. Chew et al., BAK/BAX macropores facilitate mitochondrial herniation and mtDNA efflux during apoptosis, Science, vol.359, p.6047, 2018.

E. Kayser, M. M. Sedensky, P. G. Morgan, and C. L. Hoppel, Mitochondrial Oxidative Phosphorylation Is Defective in the Long-lived Mutant clk-1, J. Biol. Chem, vol.279, pp.54479-54486, 2004.

K. Jason, M. Jeffery, and D. , Regulated Necrotic Cell Death, Circulation Research, vol.116, pp.1800-1809, 2015.

T. Eleftheriadis, G. Pissas, V. Liakopoulos, and I. Stefanidis, Cytochrome c as a Potentially Clinical Useful Marker of Mitochondrial and Cellular Damage, Frontiers in Immunology, vol.7, 2016.

R. Jemmerson, B. Laplante, and A. Treeful, Release of intact, monomeric cytochrome c from apoptotic and necrotic cells, Cell Death Differ, vol.9, pp.538-548, 2002.

D. G. Phinney, M. Di-giuseppe, J. Njah, E. Sala, S. Shiva et al., Mesenchymal stem cells use extracellular vesicles to outsource mitophagy and shuttle microRNAs, Nature Communications, vol.6, 2015.

E. L. Mills, B. Kelly, and L. A. O'neill, Mitochondria are the powerhouses of immunity, Nature Immunology, vol.18, pp.488-498, 2017.

A. Rodríguez-nuevo and A. Zorzano, The sensing of mitochondrial DAMPs by nonimmune cells, Cell Stress, vol.3, pp.195-207, 2019.

S. Grazioli and J. Pugin, Mitochondrial Damage-Associated Molecular Patterns: From Inflammatory Signaling to Human Diseases, Frontiers in Immunology, vol.9, p.832, 2018.

R. B. Seth, L. Sun, C. Ea, and Z. J. Chen, Identification and Characterization of MAVS, a Mitochondrial Antiviral Signaling Protein that Activates NF-?B and IRF3, Cell, vol.122, pp.669-682, 2005.

R. Zhou, A. S. Yazdi, P. Menu, and J. Tschopp, A role for mitochondria in NLRP3 inflammasome activation, Nature, vol.469, pp.221-225, 2011.

A. Rodriguez, J. Nakhle, E. Griessinger, and M. Vignais, Intercellular mitochondria trafficking highlighting the dual role of mesenchymal stem cells as both sensors and rescuers of tissue injury, Cell Cycle, vol.17, pp.712-721, 2018.
URL : https://hal.archives-ouvertes.fr/inserm-01855876

M. Mahrouf-yorgov, L. Augeul, C. C. Silva, M. Jourdan, M. Rigolet et al., Mesenchymal stem cells sense mitochondria released from damaged cells as danger signals to activate their rescue properties, Cell Death and Differentiation, vol.24, pp.1224-1238, 2017.
URL : https://hal.archives-ouvertes.fr/hal-01827519

M. Vignais, A. Caicedo, J. Brondello, and C. Jorgensen, Cell Connections by Tunneling Nanotubes: Effects of Mitochondrial Trafficking on Target Cell Metabolism, Homeostasis, and Response to Therapy, vol.2017, 2017.
URL : https://hal.archives-ouvertes.fr/hal-01759757

H. Han, J. Hu, Q. Yan, J. Zhu, Z. Zhu et al., Bone marrowderived mesenchymal stem cells rescue injured H9c2 cells via transferring intact mitochondria through tunneling nanotubes in an in vitro simulated ischemia/reperfusion model, Mol Med Rep, vol.13, pp.1517-1524, 2016.

K. Liu, K. Ji, L. Guo, W. Wu, H. Lu et al., Mesenchymal stem cells rescue injured endothelial cells in an in vitro ischemia-reperfusion model via tunneling nanotube like structure-mediated mitochondrial transfer, Microvasc. Res, vol.92, pp.10-18, 2014.

E. Y. Plotnikov, T. G. Khryapenkova, S. I. Galkina, G. T. Sukhikh, and D. B. Zorov, Cytoplasm and organelle transfer between mesenchymal multipotent stromal cells and renal tubular cells in co-culture, Experimental Cell Research, vol.316, pp.2447-2455, 2010.

A. Acquistapace, T. Bru, P. Lesault, F. Figeac, A. E. Coudert et al., Human Mesenchymal Stem Cells Reprogram Adult Cardiomyocytes Toward a Progenitor-Like State Through Partial Cell Fusion and Mitochondria Transfer, STEM CELLS, vol.29, pp.812-824, 2011.
URL : https://hal.archives-ouvertes.fr/inserm-00591072

L. Ippolito, A. Morandi, M. L. Taddei, M. Parri, G. Comito et al., Cancer-associated fibroblasts promote prostate cancer malignancy via metabolic rewiring and mitochondrial transfer, Oncogene, vol.38, pp.5339-5355, 2019.

A. S. Tan, J. W. Baty, L. Dong, A. Bezawork-geleta, B. Endaya et al., Mitochondrial genome acquisition restores respiratory function and tumorigenic potential of cancer cells without mitochondrial DNA, Cell Metab, vol.21, pp.81-94, 2015.

J. Pasquier, B. S. Guerrouahen, H. Thawadi, P. Ghiabi, M. Maleki et al., Preferential transfer of mitochondria from endothelial to cancer cells through tunneling nanotubes modulates chemoresistance, J Transl Med, vol.11, p.94, 2013.
URL : https://hal.archives-ouvertes.fr/inserm-00828594

E. E. Kesner, A. Saada-reich, and H. Lorberboum-galski, Characteristics of Mitochondrial Transformation into Human Cells. Scientific Reports, vol.6, 2016.

D. Patel, J. Rorbach, K. Downes, M. J. Szukszto, M. L. Pekalski et al., Macropinocytic entry of isolated mitochondria in epidermal growth factor-activated human osteosarcoma cells, Scientific Reports, vol.7, p.12886, 2017.

T. Kitani, D. Kami, S. Matoba, and S. Gojo, Internalization of isolated functional mitochondria: involvement of macropinocytosis, Journal of Cellular and Molecular Medicine, vol.18, pp.1694-1703, 2014.

E. Boilard, A. Duchez, and A. Brisson, The diversity of platelet microparticles, Curr. Opin. Hematol, vol.22, pp.437-444, 2015.

C. Hsu, L. Tseng, and H. Lee, Role of mitochondrial dysfunction in cancer progression, Exp Biol Med (Maywood), vol.241, pp.1281-1295, 2016.

H. Lee, S. Li, J. Lin, C. Wu, D. Yeh et al., Somatic mutations in the D-loop and decrease in the copy number of mitochondrial DNA in human hepatocellular carcinoma, Mutat. Res, vol.547, pp.71-78, 2004.

C. Wu, P. Yin, W. Hung, A. F. Li, S. Li et al., Mitochondrial DNA mutations and mitochondrial DNA depletion in gastric cancer, Genes Chromosomes Cancer, vol.44, pp.19-28, 2005.

L. Tseng, P. Yin, C. Chi, C. Hsu, C. Wu et al., Mitochondrial DNA mutations and mitochondrial DNA depletion in breast cancer, Genes Chromosomes Cancer, vol.45, pp.629-638, 2006.

M. M. Kim, J. D. Clinger, B. G. Masayesva, P. K. Ha, M. L. Zahurak et al., Mitochondrial DNA quantity increases with histopathologic grade in premalignant and malignant head and neck lesions, Clin. Cancer Res, vol.10, pp.8512-8515, 2004.

C. Lin, S. Chang, L. Wang, T. Chou, W. Hsu et al., The role of mitochondrial DNA alterations in esophageal squamous cell carcinomas, J. Thorac. Cardiovasc. Surg, vol.139, pp.189-197, 2010.

K. L. Hertweck and S. Dasgupta, The Landscape of mtDNA Modifications in Cancer: A Tale of Two Cities, Front. Oncol, vol.7, 2017.

M. Brandon, P. Baldi, and D. C. Wallace, Mitochondrial mutations in cancer, Oncogene, vol.25, pp.4647-4662, 2006.

A. Chatterjee, E. Mambo, and D. Sidransky, Mitochondrial DNA mutations in human cancer, Oncogene, vol.25, pp.4663-4674, 2006.

O. Warburg, On the Origin of Cancer Cells, Science, vol.123, pp.309-314, 1956.

W. Zong, J. D. Rabinowitz, and E. White, Mitochondria and Cancer, Molecular Cell, vol.61, pp.667-676, 2016.

S. Matoba, J. Kang, W. D. Patino, A. Wragg, M. Boehm et al., regulates mitochondrial respiration, Science, vol.312, pp.1650-1653, 2006.

K. Ksi??akowska-?akoma, M. ?y?a, and J. R. Wilczy?ski, Mitochondrial dysfunction in cancer, Prz Menopauzalny, vol.13, pp.136-144, 2014.

S. Vyas, E. Zaganjor, and M. C. Haigis, Mitochondria and Cancer. Cell, vol.166, pp.555-566, 2016.

P. Maycotte, A. Marín-hernández, M. Goyri-aguirre, M. Anaya-ruiz, J. Reyes-leyva et al., Mitochondrial dynamics and cancer, vol.39, p.1010428317698391, 2017.

G. Arismendi-morillo, Electron microscopy morphology of the mitochondrial network in human cancer, The International Journal of Biochemistry & Cell Biology, vol.41, pp.2062-2068, 2009.

A. Lièvre, C. Chapusot, A. Bouvier, F. Zinzindohoué, F. Piard et al., Clinical Value of Mitochondrial Mutations in Colorectal Cancer. JCO, vol.23, pp.3517-3525, 2005.

. Résumé,

, Des facteurs non solubles tels que l'ADN circulant et les vésicules extracellulaires ont récemment été ajoutés à la liste de ces composants et ont fait l'objet d'études approfondies en raison de leur rôle dans la communication intercellulaire. Or, l'ADN circulant (ADNcir) est composé de fragments d'ADN libres ou associés à d'autres particules, libérés par tous les types cellulaires. Cet ADN est non seulement de l'ADN génomique mais aussi de l'ADN mitochondrial extra-chromosomique. De nombreux travaux réalisés au cours des dernières années indiquent que l'analyse quantitative et qualitative de l'ADNcir représente une avancée dans les applications cliniques en tant que biomarqueur non invasif de diagnostic, de pronostic et de suivi thérapeutique. Cependant, malgré l'avenir prometteur de cet ADNcir dans les applications cliniques, notamment en oncologie, les connaissances sur ses origines, Le plasma transporte des cellules sanguines avec un mélange de composés, y compris les nutriments, déchets, anticorps, et messagers chimiques...dans tout l'organisme

, En examinant l'intégrité de cet ADN, ainsi que la taille et la densité des structures associées, ce travail a révélé la présence de particules denses d'une taille supérieure à 0,2 µm contenant des génomes mitochondriaux complets et non fragmentés. Nous avons caractérisé ces structures notamment par microscopie électronique et cytométrie en flux et nous avons identifié des mitochondries intactes dans le milieu extracellulaire in vitro et ex-vivo (dans des échantillons de plasma d'individus sains), Le principal objectif de ma thèse a été d'identifier et de caractériser les propriétés structurales de l'ADN extracellulaire d'origine mitochondrial

, dont 1-une étude visant à évaluer l'influence des paramètres pré-analytiques et démographiques sur la quantification d'ADNcir d'origine nucléaire et mitochondrial sur une cohorte composée de 104 individus sains et 118 patients atteints de cancer colorectal métastatique, 2-une étude dont l'objectif était d'évaluer l'influence de l'hypoxie sur le relargage de l'ADN circulant in vitro et in vivo, et 3-une étude visant à évaluer le potentiel de l'analyse de l'ADN, Par ailleurs, j'ai participé à d'autres travaux réalisées dans l'équipe

, Ce manuscrit présente une synthèse récente de la littérature sur l'ADNcir, ses différents mécanismes de relargage, qui vont de pair avec la caractérisation structurelle de cet ADN, ses aspects fonctionnels et ses différentes applications en cliniques. De plus, cette thèse apporte des connaissances nouvelles sur la structure de l'ADN mitochondrial extracellulaire tout en ouvrant de nouvelles pistes de réflexion notamment sur l'impact que pourrait avoir la présence de ces structures circulantes sur la communication cellulaire