G. Defossez, L. Guyader-peyrou, S. Uhry, Z. Grosclaude, P. Remontet et al., Estimations nationales de l'incidence et de la mortalité par cancer en France métropolitaine entre 1990 et 2018 / 2019 / Maladies chroniques et traumatismes / Rapports et synthèses / Publications et outils / Accueil, 2019.

D. C. Grossman, S. J. Curry, D. K. Owens, M. J. Barry, K. W. Davidson et al., Screening for Ovarian Cancer, JAMA [Internet], vol.319, issue.6, p.588, 2018.

A. Cowppli-bony, Z. Uhry, L. Remontet, A. Guizard, N. Voirin et al., Survie des personnes atteintes de cancer en France métropolitaine 1989-2013 -Partie 1 : tumeurs solides, 2016.

, Les cancers en France en 2018 -L'essentiel des faits et chiffres (édition 2019) -Ref : ETKAFR19 [Internet, 2019.

R. Kurman, M. Carcangiu, S. Herrington, and R. Young, WHO classification of tumours of female reproductive organs, 2014.

B. M. Reid, J. B. Permuth, and T. A. Sellers, Epidemiology of ovarian cancer: a review, 2017.

T. R. Soong, B. E. Howitt, N. Horowitz, M. R. Nucci, and C. P. Crum, The fallopian tube, "precursor escape" and narrowing the knowledge gap to the origins of high-grade serous carcinoma, Gynecol Oncol, vol.152, issue.2, pp.426-459, 2019.

M. F. Fathalla, . Incessant-ovulation-a-factor, . In, and . Neoplasia-?-lancet,

M. F. Fathalla, Incessant ovulation and ovarian cancer -a hypothesis re-visited. Facts, views Vis ObGyn, vol.5, pp.292-299, 2013.

L. J. Havrilesky, P. G. Moorman, W. J. Lowery, J. M. Gierisch, R. R. Coeytaux et al., Oral Contraceptive Pills as Primary Prevention for Ovarian Cancer, Obstet Gynecol, 2013.

. Jul, , vol.122, pp.139-186, 2019.

J. Kim, E. Park, O. Kim, J. Schilder, D. Coffey et al., Cell Origins of High-Grade Serous Ovarian Cancer. Cancers (Basel) [Internet], vol.10, p.433, 2018.

L. Dubeau, The cell of origin of ovarian epithelial tumors and the ovarian surface epithelium dogma: does the emperor have no clothes? Gynecol Oncol, 1999.

W. Cheng, J. Liu, H. Yoshida, D. Rosen, and H. Naora, Lineage infidelity of epithelial ovarian cancers is controlled by HOX genes that specify regional identity in the reproductive tract, Nat Med, vol.11, issue.5, pp.531-538, 2005.

P. S. Tanwar, G. Mohapatra, S. Chiang, D. A. Engler, L. Zhang et al., Loss of LKB1 and PTEN tumor suppressor genes in the ovarian surface epithelium induces papillary serous ovarian cancer, Carcinogenesis, vol.35, issue.3, p.491, 2003.

E. E. Meserve, J. Brouwer, and C. P. Crum, Serous tubal intraepithelial neoplasia: the concept and its application, vol.30, pp.710-731, 2017.

J. Piek, P. J. Van-diest, R. P. Zweemer, J. W. Jansen, R. Poort-keesom et al., Dysplastic changes in prophylactically removed Fallopian tubes of women predisposed to developing ovarian cancer, J Pathol, vol.195, issue.4, pp.451-457, 2001.

Y. Lee, A. Miron, R. Drapkin, M. Nucci, F. Medeiros et al., A candidate precursor to serous carcinoma that originates in the distal fallopian tube, J Pathol, vol.211, issue.1, pp.26-35, 2007.

D. W. Kindelberger, Y. Lee, A. Miron, M. S. Hirsch, C. Feltmate et al., Intraepithelial carcinoma of the fimbria and pelvic serous carcinoma: Evidence for a causal relationship, Am J Surg Pathol, vol.31, issue.2, pp.161-170, 2007.

S. I. Labidi-galy, E. Papp, D. Hallberg, N. Niknafs, V. Adleff et al., High grade serous ovarian carcinomas originate in the fallopian tube, Nat Commun, vol.8, issue.1, p.1093, 2017.

T. R. Soong, B. E. Howitt, A. Miron, N. S. Horowitz, F. Campbell et al., Evidence for lineage continuity between early serous proliferations (ESPs) in the Fallopian tube and disseminated high-grade serous carcinomas, J Pathol, vol.246, issue.3, pp.344-51, 2009.

R. Perets, G. A. Wyant, K. W. Muto, J. G. Bijron, B. B. Poole et al., Transformation of the Fallopian Tube Secretory Epithelium Leads to High-Grade Serous Ovarian Cancer in Brca;Tp53;Pten Models. Cancer Cell, vol.24, pp.751-65, 2013.

W. Xian, A. Miron, M. Roh, D. R. Semmel, Y. Yassin et al., The Li-Fraumeni syndrome (LFS): a model for the initiation of p53 signatures in the distal Fallopian tube, J Pathol, vol.220, issue.1, pp.17-23, 2010.

P. D. Pharoah and B. A. Ponder, The genetics of ovarian cancer, Best Pract Res Clin Obstet Gynaecol, vol.16, issue.4, pp.449-68, 2002.

T. Walsh, S. Casadei, M. K. Lee, C. C. Pennil, A. S. Nord et al., Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing, Proc Natl Acad Sci, vol.108, issue.44, pp.18032-18039, 2011.

Y. Miki, J. Swensen, D. Shattuck-eidens, P. A. Futreal, K. Harshman et al., A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1, Science

R. Wooster, G. Bignell, J. Lancaster, S. Swift, S. Seal et al., Identification of the breast cancer susceptibility gene BRCA2, Nature, vol.378, issue.6559, pp.789-92, 1995.

A. C. Antoniou, S. Casadei, T. Heikkinen, D. Barrowdale, K. Pylkäs et al., Breast-Cancer Risk in Families with Mutations in PALB2, N Engl J Med, vol.371, issue.6, pp.497-506, 2014.

V. Bonadona, B. Bonaïti, S. Olschwang, S. Grandjouan, L. Huiart et al., Cancer Risks Associated With Germline Mutations in MLH1 MSH2 MSH6 Genes in Lynch Syndrome, JAMA, vol.305, issue.22, p.2304, 2011.
URL : https://hal.archives-ouvertes.fr/hal-00780536

I. Gorodetska, I. Kozeretska, A. Dubrovska, and . Brca-genes, The Role in Genome Stability, Cancer Stemness and Therapy Resistance, J Cancer, vol.10, 2019.

J. M. Noh, D. H. Choi, H. Baek, S. J. Nam, J. E. Lee et al., Associations between BRCA Mutations in High-Risk Breast Cancer Patients and Familial Cancers Other than Breast or Ovary, J Breast Cancer, vol.15, issue.3, pp.283-290, 2012.

G. Stelzer, N. Rosen, I. Plaschkes, S. Zimmerman, M. Twik et al., The GeneCards Suite: From Gene Data Mining to Disease Genome Sequence Analyses, Current Protocols in Bioinformatics

N. J. Hoboken and . Usa, , 2016.

, , vol.33

P. Gaudet, P. Michel, M. Zahn-zabal, A. Britan, I. Cusin et al., The neXtProt knowledgebase on human proteins: 2017 update, Nucleic Acids Res, vol.45, issue.D1, pp.177-82, 2017.

R. Roy, J. Chun, and S. N. Powell, BRCA1 and BRCA2: different roles in a common pathway of genome protection HHS Public Access, 2019.

M. S. Cline, R. G. Liao, M. T. Parsons, P. B. Alquaddoomi, F. Antoniou et al., BRCA Exchange as a global resource for variants in BRCA1 and BRCA2, vol.14, p.1007752, 2018.

Y. Laitman, B. Feng, I. M. Zamir, J. N. Weitzel, P. Duncan et al., Haplotype analysis of the 185delAG BRCA1 mutation in ethnically diverse populations, Eur J Hum Genet, 2013.

. Feb, , vol.21, pp.212-218, 2019.

N. Hamel, B. Feng, L. Foretova, D. Stoppa-lyonnet, S. A. Narod et al., On the origin and diffusion of BRCA1 c.5266dupC (5382insC) in European populations, Eur J Hum Genet, vol.19, issue.3, pp.300-306, 2011.
URL : https://hal.archives-ouvertes.fr/hal-00828528

C. Heramb, T. Wangensteen, E. M. Grindedal, S. L. Ariansen, S. Lothe et al., BRCA1 and BRCA2 mutation spectrum -an update on mutation distribution in a large cancer genetics clinic in Norway, Hered Cancer Clin Pract, vol.16, issue.1, 2018.

J. Hoeijmakers, Genome maintenance mechanisms for preventing cancer, Nature

J. Seol, E. Y. Shim, and S. E. Lee, Microhomology-mediated end joining: Good, bad and ugly

C. Chen, W. Feng, P. X. Lim, E. M. Kass, and M. Jasin, Homology-Directed Repair and the Role of BRCA1, BRCA2, and Related Proteins in Genome Integrity and Cancer, Annu Rev Cancer Biol [Internet], vol.2, issue.1, pp.313-349, 2018.

K. B. Kuchenbaecker, J. L. Hopper, D. R. Barnes, K. Phillips, T. M. Mooij et al., Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers, JAMA, vol.317, issue.23, p.2402, 2017.

A. Meindl, H. Hellebrand, C. Wiek, V. Erven, B. Wappenschmidt et al., Germline mutations in breast and ovarian cancer pedigrees establish RAD51C as a human cancer susceptibility gene, Nat Genet, vol.42, issue.5, pp.410-414, 2010.

C. Loveday, C. Turnbull, E. Ruark, R. Xicola, E. Ramsay et al., Germline RAD51C mutations confer susceptibility to ovarian cancer, Nat Genet, vol.44, issue.5, pp.475-481, 2012.

H. Song, E. Dicks, S. J. Ramus, J. P. Tyrer, M. P. Intermaggio et al., Contribution of Germline Mutations in the RAD51B , RAD51C , and RAD51D Genes to Ovarian Cancer in the Population, J Clin Oncol, vol.33, issue.26, pp.2901-2908, 2015.

C. Loveday, C. Turnbull, E. Ramsay, D. Hughes, E. Ruark et al., Germline mutations in RAD51D confer susceptibility to ovarian cancer, Nat Genet, 2011.

S. B. Cantor, D. W. Bell, S. Ganesan, E. M. Kass, R. Drapkin et al., BACH1, a novel helicase-like protein, interacts directly with BRCA1 and contributes to its DNA repair function, vol.105, pp.149-60, 2001.

T. Rafnar, D. F. Gudbjartsson, P. Sulem, A. Jonasdottir, A. Sigurdsson et al., Mutations in BRIP1 confer high risk of ovarian cancer, Nat Genet, vol.43, issue.11, pp.1104-1111, 2011.

N. Weber-lassalle, J. Hauke, J. Ramser, L. Richters, E. Groß et al., BRIP1 loss-offunction mutations confer high risk for familial ovarian cancer, but not familial breast cancer, Breast Cancer Res [Internet], vol.20, issue.1, 2018.

J. Moretta, P. Berthet, V. Bonadona, O. Caron, O. Cohen-haguenauer et al., Recommandations françaises du Groupe Génétique et Cancer pour l'analyse en panel de gènes dans les prédispositions héréditaires au cancer du sein ou de l'ovaire. Bull Cancer [Internet], vol.105, pp.907-924, 2018.

A. Finch, M. Beiner, J. Lubinski, H. T. Lynch, P. Moller et al., Salpingo-oophorectomy and the Risk of Ovarian, Fallopian Tube, and Peritoneal Cancers in Women With a BRCA1 or BRCA2 Mutation, JAMA, vol.296, issue.2, p.185, 2006.

, Femmes porteuses d'une mutation de BRCA1 ou BRCA2 / Détection précoce du cancer du sein et des annexes et stratégies de réduction du risque -Ref : RECOBRCA17

M. J. Casey, C. Synder, C. Bewtra, S. A. Narod, P. Watson et al., Intra-abdominal carcinomatosis after prophylactic oophorectomy in women of hereditary breast ovarian cancer syndrome kindreds associated with BRCA1 and BRCA2 mutations, Gynecol Oncol, vol.97, issue.2, pp.457-67, 2005.

S. M. Domchek, T. M. Friebel, C. F. Singer, G. Evans, D. Lynch et al., Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality, JAMA -J Am Med Assoc, vol.304, issue.9, pp.967-75, 2010.

J. T. Henderson, E. M. Webber, and G. F. Sawaya, Screening for Ovarian Cancer, JAMA [Internet], vol.319, issue.6, p.595, 2018.

. Mandel-p and . Metais-p, Les acides nucléiques du plasma sanguin chez l'homme. C R Seances Soc Biol Fil, vol.142, pp.241-244, 1948.

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, issue.3, pp.646-50, 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, vol.51, pp.2116-2136, 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, issue.5, pp.318-340, 1989.

V. Vasioukhin, P. Anker, P. Maurice, J. Lyautey, C. Lederrey et al., Point mutations of the Nras gene in the blood plasma DNA of patients with myelodysplastic syndrome or acute myelogenous leukaemia, Br J Haematol, vol.86, issue.4, pp.774-783, 1994.

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&quot, Nat Rev Cancer, 1994.

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, Nat Commun, vol.9, issue.1, 2018.

J. Phallen, M. Sausen, V. Adleff, A. Leal, C. Hruban et al., Direct detection of early-stage cancers using circulating tumor DNA, Sci Transl Med, vol.9, issue.403, p.2415, 2017.

F. Mouliere, D. Chandrananda, A. M. Piskorz, E. K. Moore, J. Morris et al., Enhanced detection of circulating tumor DNA by fragment size analysis, Sci Transl Med [Internet], vol.10, issue.466, p.4921, 2018.

A. R. Thierry, S. El-messaoudi, P. B. Gahan, P. Anker, and M. Stroun, Origins, structures, and functions of circulating DNA in oncology, Cancer Metastasis Rev, vol.35, issue.3, pp.347-76, 2016.
URL : https://hal.archives-ouvertes.fr/hal-02299112

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, Sci Transl Med, vol.6, issue.224, pp.224-248, 2014.

S. Hellwig, D. A. Nix, K. M. Gligorich, O. Shea, J. M. Thomas et al., Automated size selection for short cell-free DNA fragments enriches for circulating tumor DNA and improves error correction during next generation sequencing, vol.13, p.197333, 2018.

M. Stroun, P. Anker, J. Lyautey, C. Lederrey, and P. A. Maurice, Isolation and characterization of DNA from the plasma of cancer patients, Eur J Cancer Clin Oncol, 1987.

J. D. Cohen, L. Li, Y. Wang, C. Thoburn, B. Afsari et al., Detection and localization of surgically resectable cancers with a multi-analyte blood test, Science [Internet], vol.359, issue.6378, pp.926-956, 2018.

A. Yokoi, Y. Yoshioka, A. Hirakawa, Y. Yamamoto, M. Ishikawa et al., A combination of circulating miRNAs for the early detection of ovarian cancer, Oncotarget, vol.8, issue.52, pp.89811-89834, 2017.

M. Widschwendter, M. Zikan, B. Wahl, H. Lempiäinen, T. Paprotka et al., The potential of circulating tumor DNA methylation analysis for the early detection and management of ovarian cancer, Genome Med, vol.9, issue.1, p.116, 2017.

D. Bell, A. Berchuck, M. Birrer, J. Chien, D. W. Cramer et al., Integrated genomic analyses of ovarian carcinoma, Nature, vol.474, issue.7353, pp.609-624, 2011.

A. J. Bronkhorst, J. Aucamp, and P. J. Pretorius, Cell-free DNA: Preanalytical variables, Clinica Chimica Acta. Elsevier B.V, vol.450, pp.243-53, 2015.

A. Patch, C. E. Etemadmoghadam, D. Garsed, D. W. George, J. Fereday et al., Wholegenome characterization of chemoresistant ovarian cancer, Nature, vol.521, issue.7553, pp.489-94, 2015.

Y. K. Wang, A. Bashashati, M. S. Anglesio, D. R. Cochrane, D. S. Grewal et al., Genomic consequences of aberrant DNA repair mechanisms stratify ovarian cancer histotypes, Nat Genet, vol.49, issue.6, pp.856-65, 2017.

V. Plagnol, J. Curtis, M. Epstein, K. Y. Mok, E. Stebbings et al., A robust model for read count data in exome sequencing experiments and implications for copy number variant calling, Bioinformatics, vol.28, issue.21, pp.2747-54, 2012.

S. Richards, N. Aziz, S. Bale, D. Bick, S. Das et al., Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology, Genet Med, vol.17, issue.5, pp.405-429, 2015.

H. Jung, J. A. Lefferts, and G. J. Tsongalis, Utilization of the oncoscan microarray assay in cancer diagnostics, Appl Cancer Res, vol.37, issue.1, 2017.

K. A. Hoadley, C. Yau, T. Hinoue, D. M. Wolf, A. J. Lazar et al., Cell-of-Origin Patterns Dominate the Molecular Classification of 10,000 Tumors from 33 Types of, Cancer. Cell, vol.173, issue.2, pp.291-304, 2018.

O. Østrup, L. B. Ahlborn, U. Lassen, M. Mau-sørensen, and F. C. Nielsen, Detection of copy number alterations in cell-free tumor DNA from plasma. BBA Clin, vol.7, pp.120-126, 2017.

J. J. Salk, K. Loubet-senear, E. Maritschnegg, C. C. Valentine, L. N. Williams et al., Ultra-Sensitive TP53 Sequencing for Cancer Detection Reveals Progressive Clonal Selection in Normal Tissue over a Century of Human Lifespan, Cell Rep, vol.28, issue.1, pp.132-144, 2019.
URL : https://hal.archives-ouvertes.fr/hal-02180268

A. Fowler, S. Mahamdallie, E. Ruark, S. Seal, R. E. Clarke et al., Accurate clinical detection of exon copy number variants in a targeted NGS panel using DECoN. Wellcome Open Res, vol.1, 2016.

A. Piskorz, K. K. Lin, J. A. Morris, E. Mann, A. M. Oza et al., Feasibility of monitoring response to the PARP inhibitor rucaparib with targeted deep sequencing of circulating tumor DNA (ctDNA) in women with high-grade serous carcinoma on the ARIEL2 trial, J Clin Oncol, vol.34, pp.5549-5549, 2016.

E. L. Christie, S. Fereday, K. Doig, S. Pattnaik, S. Dawson et al.,

, Germline Mutations Detected in Circulating Tumor DNA From Patients With High-Grade Serous Ovarian Cancer, J Clin Oncol, vol.35, issue.12, pp.1274-80, 2017.

M. R. Radke, J. D. Isaacson, K. K. Lin, L. Vo, M. I. Harrell et al., BRCA Reversion Mutations in Circulating Tumor DNA Predict Primary and Acquired Resistance to the PARP Inhibitor Rucaparib in High-Grade Ovarian Carcinoma, Cancer Discov, vol.9, issue.2, pp.210-219, 2018.

E. Pereira, O. Camacho-vanegas, S. Anand, R. Sebra, S. C. Camacho et al., Personalized circulating tumor DNA biomarkers dynamically predict treatment response and survival in gynecologic cancers, PLoS One, vol.10, issue.12, 2015.

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, 2016.

Y. M. Kim, S. W. Lee, Y. J. Lee, H. Y. Lee, J. E. Lee et al., Prospective study of the efficacy and utility of TP53 mutations in circulating tumor DNA as a non-invasive biomarker of treatment response monitoring in patients with high-grade serous ovarian carcinoma, J Gynecol Oncol, vol.30, issue.3, 2019.

G. Macintyre, T. E. Goranova, D. Silva, D. Ennis, D. Piskorz et al., Copy number signatures and mutational processes in ovarian carcinoma, Nat Genet [Internet], vol.50, issue.9, pp.1262-70, 2018.

M. Nakabayashi, A. Kawashima, R. Yasuhara, Y. Hayakawa, S. Miyamoto et al., Massively parallel sequencing of cell-free DNA in plasma for detecting gynaecological tumour-associated copy number alteration Correction: Publisher Correction, vol.8, p.11205, 2018.

A. Vanderstichele, P. Busschaert, D. Smeets, C. Landolfo, E. Van-nieuwenhuysen et al., Chromosomal Instability in Cell-Free DNA as a Highly Specific Biomarker for Detection of Ovarian Cancer in Women with Adnexal Masses, Clin Cancer Res, 2017.

C. J. Creighton, A. Hernandez-herrera, A. Jacobsen, D. A. Levine, P. Mankoo et al., Integrated Analyses of microRNAs Demonstrate Their Widespread Influence on Gene Expression in High-Grade Serous Ovarian Carcinoma, PLoS One

, , vol.7, p.34546, 2019.

, Mutations TP53 de faible fréquence allélique : peut-on s'affranchir de la biopsie pour différencier une mosaïque d'une hématopoïèse clonale ? In: Assise de génétique 2020, 2020.

B. Kim, S. Lee, and J. R. Choi, Somatic mosaic truncating mutations of PPM1D in blood can result from expansion of a mutant clone under selective pressure of chemotherapy, p.2020, 2019.

,

J. I. Hsu, T. Dayaram, A. Tovy, D. Braekeleer, E. Jeong et al., PPM1D Mutations Drive Clonal Hematopoiesis in Response to Cytotoxic Chemotherapy, Cell Stem Cell, vol.23, issue.5, pp.700-713, 2018.

. Serment-de-galien-je-jure, en présence des maîtres de la Faculté, des conseillers de l'ordre des Pharmaciens et de mes condisciples

, D'honorer ceux qui m'ont instruit(e) dans les préceptes de mon art et de leur témoigner ma reconnaissance en restant fidèle à leur enseignement

, intérêt de la santé publique, ma profession avec conscience et de respecter non seulement la législation en vigueur, mais aussi les règles de l'honneur

, De ne jamais oublier ma responsabilité et mes devoirs envers le malade et sa dignité humaine

, En aucun cas, je ne consentirai à utiliser mes connaissances et mon état pour corrompre les moeurs et favoriser des actes criminels

, Que les hommes m'accordent leur estime si je suis fidèle à mes promesses

, Que je sois couvert d'opprobre et méprisé de mes confrères si j'y manque