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Cells of origin of ovarian cancer: ovarian surface epithelium or fallopian tube?

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Abstract

Objective

Ovarian cancer is the fifth most common cancer in women and one of the leading causes of death from gynecological malignancies. Despite of its clinical importance, ovarian tumorigenesis is poorly understood and prognosis remains poor. This is particularly true for the most common type of ovarian cancer, high-grade serous ovarian cancer.

Results

Two models are considered, whether it arises from the ovarian surface epithelium or from the fallopian tube. The first model is based on (1) the pro-inflammatory environment caused by ovulation events, (2) the expression pattern of ovarian inclusion cysts, and (3) biomarkers that are shared by the ovarian surface epithelium and malignant growth. The model suggesting a non-ovarian origin is based on (1) tubal precursor lesions, (2) genetic evidence of BRCA1/2 mutation carriers, and (3) recent animal studies. Neither model has clearly demonstrated superiority over the other. Therefore, one can speculate that high-grade serous ovarian cancer may arise from two different sites that undergo similar changes. Both tissues are derived from the same embryologic origin, which may explain how progenitor cells from different sites can respond similar to stimuli within the ovaries. However, distinct molecular drivers, such as BRCA deficiency, may still preferentially arise from one site of origin as precancerous mutations are frequently seen in the fallopian tube.

Conclusions

Confirming the origin of ovarian cancer has important clinical implications when deciding on cancer risk-reducing prophylactic surgery. It will be important to identify key biomarker to uncover the sequence of ovarian tumorigenesis.

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References

  1. Wimberger P, Lehmann N, Kimmig R, Burges A, Meier W, Du Bois A, Group AGOOCS (2007) Prognostic factors for complete debulking in advanced ovarian cancer and its impact on survival. An exploratory analysis of a prospectively randomized phase III study of the Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Cancer Study Group (AGO-OVAR). Gynecol Oncol 106(1):69–74

    Article  PubMed  Google Scholar 

  2. Prat J (2012) New insights into ovarian cancer pathology. Ann Oncol 23(Suppl 10):x111–x117

    Article  PubMed  Google Scholar 

  3. Králíčková M, Vetvicka V (2014) Endometriosis and ovarian cancer. World J Clin Oncol 5(5):800–805

    Article  PubMed  PubMed Central  Google Scholar 

  4. Young RH (2006) From krukenberg to today: the ever present problems posed by metastatic tumors in the ovary: part I. Historical perspective, general principles, mucinous tumors including the krukenberg tumor. Adv Anat Pathol 13(5):205–227

    Article  PubMed  Google Scholar 

  5. Karnezis AN, Cho KR, Gilks CB, Pearce CL, Huntsman DG (2017) The disparate origins of ovarian cancers: pathogenesis and prevention strategies. Nat Rev Cancer 17(1):65–74

    Article  CAS  PubMed  Google Scholar 

  6. Vang R, Shih IM, Kurman RJ (2009) Ovarian low-grade and high-grade serous carcinoma: pathogenesis, clinicopathologic and molecular biologic features, and diagnostic problems. Adv Anat Pathol 16(5):267–282

    Article  PubMed  PubMed Central  Google Scholar 

  7. Barnes B, Berta J, Buttmann-Schweiger N, Liebig J, Jordan S, Kramwinkel K, Niemann H, Nowossadeck E, Poethko-Müller C, Prytz F, Rattay P, Schönfeld I, Starker A, Wienecke A, Wolf U (2016) Bericht zum Krebsgeschehen in Deutschland 2016. Robert Koch Institut, Berlin

    Google Scholar 

  8. Wimberger P, Wehling M, Lehmann N, Kimmig R, Schmalfeldt B, Burges A, Harter P, Pfisterer J, du Bois A (2010) Influence of residual tumor on outcome in ovarian cancer patients with FIGO stage IV disease: an exploratory analysis of the AGO-OVAR (Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Cancer Study Group). Ann Surg Oncol 17(6):1642–1648

    Article  PubMed  Google Scholar 

  9. Ayhan A, Kurman RJ, Yemelyanova A, Vang R, Logani S, Seidman JD, Shih IM (2009) Defining the cut point between low-grade and high-grade ovarian serous carcinomas: a clinicopathologic and molecular genetic analysis. Am J Surg Pathol 33(8):1220–1224

    Article  PubMed  PubMed Central  Google Scholar 

  10. Kim J, Coffey DM, Creighton CJ, Yu Z, Hawkins SM, Matzuk MM (2012) High-grade serous ovarian cancer arises from fallopian tube in a mouse model. Proc Natl Acad Sci USA 109(10):3921–3926

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Auersperg N (2013) The origin of ovarian cancers—hypotheses and controversies. Front Biosci (Schol Ed) 5:709–719

    Article  Google Scholar 

  12. Moser AR, Pitot HC, Dove WF (1990) A dominant mutation that predisposes to multiple intestinal neoplasia in the mouse. Science 247(4940):322–324

    Article  CAS  PubMed  Google Scholar 

  13. Holme Ø, Bretthauer M, Fretheim A, Odgaard-Jensen J, Hoff G (2013) Flexible sigmoidoscopy versus faecal occult blood testing for colorectal cancer screening in asymptomatic individuals. Cochrane Database Syst Rev 9:CD009259

    Google Scholar 

  14. Vaughan S, Coward JI, Bast RC, Berchuck A, Berek JS, Brenton JD, Coukos G, Crum CC, Drapkin R, Etemadmoghadam D, Friedlander M, Gabra H, Kaye SB, Lord CJ, Lengyel E, Levine DA, McNeish IA, Menon U, Mills GB, Nephew KP, Oza AM, Sood AK, Stronach EA, Walczak H, Bowtell DD, Balkwill FR (2011) Rethinking ovarian cancer: recommendations for improving outcomes. Nat Rev Cancer 11(10):719–725

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Auersperg N (2013) The origin of ovarian cancers—hypotheses and controversies. Front Biosci (Schol Ed) 5:709–719

    Article  Google Scholar 

  16. Kim J, Coffey DM, Creighton CJ, Yu Z, Hawkins SM, Matzuk MM (2012) High-grade serous ovarian cancer arises from fallopian tube in a mouse model. Proc Natl Acad Sci USA 109(10):3921–3926

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Fathalla MF (1971) Incessant ovulation—a factor in ovarian neoplasia? Lancet 2(7716):163

    Article  CAS  PubMed  Google Scholar 

  18. Ness RB, Grisso JA, Klapper J, Schlesselman JJ, Silberzweig S, Vergona R, Morgan M, Wheeler JE (2000) Risk of ovarian cancer in relation to estrogen and progestin dose and use characteristics of oral contraceptives. SHARE Study Group. Steroid hormones and reproductions. Am J Epidemiol 152(3):233–241

    Article  CAS  PubMed  Google Scholar 

  19. Risch HA, McLaughlin JR, Cole DE, Rosen B, Bradley L, Fan I, Tang J, Li S, Zhang S, Shaw PA, Narod SA (2006) Population BRCA1 and BRCA2 mutation frequencies and cancer penetrances: a kin-cohort study in Ontario, Canada. J Natl Cancer Inst 98(23):1694–1706

    Article  CAS  PubMed  Google Scholar 

  20. Antoniou A, Pharoah PD, Narod S, Risch HA, Eyfjord JE, Hopper JL, Loman N, Olsson H, Johannsson O, Borg A, Pasini B, Radice P, Manoukian S, Eccles DM, Tang N, Olah E, Anton-Culver H, Warner E, Lubinski J, Gronwald J, Gorski B, Tulinius H, Thorlacius S, Eerola H, Nevanlinna H, Syrjakoski K, Kallioniemi OP, Thompson D, Evans C, Peto J, Lalloo F, Evans DG, Easton DF (2003) Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet 72(5):1117–1130

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Network CGAR (2011) Integrated genomic analyses of ovarian carcinoma. Nature 474(7353):609–615

    Article  Google Scholar 

  22. Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, Liu Q, Cochran C, Bennett LM, Ding W et al (1994) A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 266(5182):66–71

    Article  CAS  PubMed  Google Scholar 

  23. Moynahan ME, Pierce AJ, Jasin M (2001) BRCA2 is required for homology-directed repair of chromosomal breaks. Mol Cell 7(2):263–272

    Article  CAS  PubMed  Google Scholar 

  24. Moynahan ME, Chiu JW, Koller BH, Jasin M (1999) Brca1 controls homology-directed DNA repair. Mol Cell 4(4):511–518

    Article  CAS  PubMed  Google Scholar 

  25. Rebbeck TR, Mitra N, Wan F, Sinilnikova OM, Healey S, McGuffog L, Mazoyer S, Chenevix-Trench G, Easton DF, Antoniou AC, Nathanson KL, Laitman Y, Kushnir A, Paluch-Shimon S, Berger R, Zidan J, Friedman E, Ehrencrona H, Stenmark-Askmalm M, Einbeigi Z, Loman N, Harbst K, Rantala J, Melin B, Huo D, Olopade OI, Seldon J, Ganz PA, Nussbaum RL, Chan SB, Odunsi K, Gayther SA, Domchek SM, Arun BK, Lu KH, Mitchell G, Karlan BY, Walsh C, Lester J, Godwin AK, Pathak H, Ross E, Daly MB, Whittemore AS, John EM, Miron A, Terry MB, Chung WK, Goldgar DE, Buys SS, Janavicius R, Tihomirova L, Tung N, Dorfling CM, van Rensburg EJ, Steele L, Neuhausen SL, Ding YC, Ejlertsen B, Gerdes AM, Hansen T, Ramón y Cajal T, Osorio A, Benitez J, Godino J, Tejada MI, Duran M, Weitzel JN, Bobolis KA, Sand SR, Fontaine A, Savarese A, Pasini B, Peissel B, Bonanni B, Zaffaroni D, Vignolo-Lutati F, Scuvera G, Giannini G, Bernard L, Genuardi M, Radice P, Dolcetti R, Manoukian S, Pensotti V, Gismondi V, Yannoukakos D, Fostira F, Garber J, Torres D, Rashid MU, Hamann U, Peock S, Frost D, Platte R, Evans DG, Eeles R, Davidson R, Eccles D, Cole T, Cook J, Brewer C, Hodgson S, Morrison PJ, Walker L, Porteous ME, Kennedy MJ, Izatt L, Adlard J, Donaldson A, Ellis S, Sharma P, Schmutzler RK, Wappenschmidt B, Becker A, Rhiem K, Hahnen E, Engel C, Meindl A, Engert S, Ditsch N, Arnold N, Plendl HJ, Mundhenke C, Niederacher D, Fleisch M, Sutter C, Bartram CR, Dikow N, Wang-Gohrke S, Gadzicki D, Steinemann D, Kast K, Beer M, Varon-Mateeva R, Gehrig A, Weber BH, Stoppa-Lyonnet D, Houdayer C, Belotti M, Gauthier-Villars M, Damiola F, Boutry-Kryza N, Lasset C, Sobol H, Peyrat JP, Muller D, Fricker JP, Collonge-Rame MA, Mortemousque I, Nogues C, Rouleau E, Isaacs C, De Paepe A, Poppe B, Claes K, De Leeneer K, Piedmonte M, Rodriguez G, Wakely K, Boggess J, Blank SV, Basil J, Azodi M, Phillips KA, Caldes T, de la Hoya M, Romero A, Nevanlinna H, Aittomäki K, van der Hout AH, Hogervorst FB, Verhoef S, Collée JM, Seynaeve C, Oosterwijk JC, Gille JJ, Wijnen JT, Gómez Garcia EB, Kets CM, Ausems MG, Aalfs CM, Devilee P, Mensenkamp AR, Kwong A, Olah E, Papp J, Diez O, Lazaro C, Darder E, Blanco I, Salinas M, Jakubowska A, Lubinski J, Gronwald J, Jaworska-Bieniek K, Durda K, Sukiennicki G, Huzarski T, Byrski T, Cybulski C, Toloczko-Grabarek A, Złowocka-Perłowska E, Menkiszak J, Arason A, Barkardottir RB, Simard J, Laframboise R, Montagna M, Agata S, Alducci E, Peixoto A, Teixeira MR, Spurdle AB, Lee MH, Park SK, Kim SW, Friebel TM, Couch FJ, Lindor NM, Pankratz VS, Guidugli L, Wang X, Tischkowitz M, Foretova L, Vijai J, Offit K, Robson M, Rau-Murthy R, Kauff N, Fink-Retter A, Singer CF, Rappaport C, Gschwantler-Kaulich D, Pfeiler G, Tea MK, Berger A, Greene MH, Mai PL, Imyanitov EN, Toland AE, Senter L, Bojesen A, Pedersen IS, Skytte AB, Sunde L, Thomassen M, Moeller ST, Kruse TA, Jensen UB, Caligo MA, Aretini P, Teo SH, Selkirk CG, Hulick PJ, Andrulis I, Consortium C (2015) Association of type and location of BRCA1 and BRCA2 mutations with risk of breast and ovarian cancer. JAMA 313(13):1347–1361

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Bowen NJ, Walker LD, Matyunina LV, Logani S, Totten KA, Benigno BB, McDonald JF (2009) Gene expression profiling supports the hypothesis that human ovarian surface epithelia are multipotent and capable of serving as ovarian cancer initiating cells. BMC Med Genom 2:71

    Article  Google Scholar 

  27. Schepers AG, Snippert HJ, Stange DE, van den Born M, van Es JH, van de Wetering M, Clevers H (2012) Lineage tracing reveals Lgr5+ stem cell activity in mouse intestinal adenomas. Science 337(6095):730–735

    Article  CAS  PubMed  Google Scholar 

  28. Barker N, Ridgway RA, van Es JH, van de Wetering M, Begthel H, van den Born M, Danenberg E, Clarke AR, Sansom OJ, Clevers H (2009) Crypt stem cells as the cells-of-origin of intestinal cancer. Nature 457(7229):608–611

    Article  CAS  PubMed  Google Scholar 

  29. Pothuri B, Leitao MM, Levine DA, Viale A, Olshen AB, Arroyo C, Bogomolniy F, Olvera N, Lin O, Soslow RA, Robson ME, Offit K, Barakat RR, Boyd J (2010) Genetic analysis of the early natural history of epithelial ovarian carcinoma. PLoS One 5(4):e10358

    Article  PubMed  PubMed Central  Google Scholar 

  30. Sharma A, Gentry-Maharaj A, Burnell M, Fourkala EO, Campbell S, Amso N, Seif MW, Ryan A, Parmar M, Jacobs I, Menon U (2012) Assessing the malignant potential of ovarian inclusion cysts in postmenopausal women within the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a prospective cohort study. BJOG 119(2):207–219

    Article  CAS  PubMed  Google Scholar 

  31. Dubeau L (1999) The cell of origin of ovarian epithelial tumors and the ovarian surface epithelium dogma: does the emperor have no clothes? Gynecol Oncol 72(3):437–442

    Article  CAS  PubMed  Google Scholar 

  32. Kindelberger DW, Lee Y, Miron A, Hirsch MS, Feltmate C, Medeiros F, Callahan MJ, Garner EO, Gordon RW, Birch C, Berkowitz RS, Muto MG, Crum CP (2007) Intraepithelial carcinoma of the fimbria and pelvic serous carcinoma: evidence for a causal relationship. Am J Surg Pathol 31(2):161–169

    Article  PubMed  Google Scholar 

  33. Kurman RJ, Shih IM (2011) Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer—shifting the paradigm. Hum Pathol 42(7):918–931

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Zeppernick F, Meinhold-Heerlein I, Shih IM (2015) Precursors of ovarian cancer in the fallopian tube: serous tubal intraepithelial carcinoma—an update. J Obstet Gynaecol Res 41(1):6–11

    Article  PubMed  Google Scholar 

  35. Piek JM, van Diest PJ, Zweemer RP, Jansen JW, Poort-Keesom RJ, Menko FH, Gille JJ, Jongsma AP, Pals G, Kenemans P, Verheijen RH (2001) Dysplastic changes in prophylactically removed Fallopian tubes of women predisposed to developing ovarian cancer. J Pathol 195(4):451–456

    Article  CAS  PubMed  Google Scholar 

  36. Piek JM, Kenemans P, Verheijen RH (2004) Intraperitoneal serous adenocarcinoma: a critical appraisal of three hypotheses on its cause. Am J Obstet Gynecol 191(3):718–732

    Article  PubMed  Google Scholar 

  37. Ahmed AA, Etemadmoghadam D, Temple J, Lynch AG, Riad M, Sharma R, Stewart C, Fereday S, Caldas C, Defazio A, Bowtell D, Brenton JD (2010) Driver mutations in TP53 are ubiquitous in high grade serous carcinoma of the ovary. J Pathol 221(1):49–56

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Singer G, Stohr R, Cope L, Dehari R, Hartmann A, Cao DF, Wang TL, Kurman RJ, Shih Ie M (2005) Patterns of p53 mutations separate ovarian serous borderline tumors and low- and high-grade carcinomas and provide support for a new model of ovarian carcinogenesis: a mutational analysis with immunohistochemical correlation. Am J Surg Pathol 29(2):218–224

    Article  PubMed  Google Scholar 

  39. Hofstetter G, Berger A, Schuster E, Wolf A, Hager G, Vergote I, Cadron I, Sehouli J, Braicu EI, Mahner S, Speiser P, Marth C, Zeimet AG, Ulmer H, Zeillinger R, Concin N (2011) Delta133p53 is an independent prognostic marker in p53 mutant advanced serous ovarian cancer. Br J Cancer 105(10):1593–1599

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Lee Y, Miron A, Drapkin R, Nucci MR, Medeiros F, Saleemuddin A, Garber J, Birch C, Mou H, Gordon RW, Cramer DW, McKeon FD, Crum CP (2007) A candidate precursor to serous carcinoma that originates in the distal fallopian tube. J Pathol 211(1):26–35

    Article  CAS  PubMed  Google Scholar 

  41. Rebbeck TR, Kauff ND, Domchek SM (2009) Meta-analysis of risk reduction estimates associated with risk-reducing salpingo-oophorectomy in BRCA1 or BRCA2 mutation carriers. J Natl Cancer Inst 101(2):80–87

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Kuhlmann JD, Baraniskin A, Hahn SA, Mosel F, Bredemeier M, Wimberger P, Kimmig R, Kasimir-Bauer S (2014) Circulating U2 small nuclear RNA fragments as a novel diagnostic tool for patients with epithelial ovarian cancer. Clin Chem 60(1):206–213

    Article  CAS  PubMed  Google Scholar 

  43. Wimberger P, Chebouti I, Kasimir-Bauer S, Lachmann R, Kuhlisch E, Kimmig R, Süleyman E, Kuhlmann JD (2014) Explorative investigation of vascular endothelial growth factor receptor expression in primary ovarian cancer and its clinical relevance. Gynecol Oncol 133(3):467–472

    Article  CAS  PubMed  Google Scholar 

  44. Barker N, Bartfeld S, Clevers H (2010) Tissue-resident adult stem cell populations of rapidly self-renewing organs. Cell Stem Cell 7(6):656–670

    Article  CAS  PubMed  Google Scholar 

  45. Ng A, Tan S, Singh G, Rizk P, Swathi Y, Tan TZ, Huang RY, Leushacke M, Barker N (2014) Lgr5 marks stem/progenitor cells in ovary and tubal epithelia. Nat Cell Biol 16(8):745–757

    Article  CAS  PubMed  Google Scholar 

  46. Yan KS, Janda CY, Chang J, Zheng GXY, Larkin KA, Luca VC, Chia LA, Mah AT, Han A, Terry JM, Ootani A, Roelf K, Lee M, Yuan J, Li X, Bolen CR, Wilhelmy J, Davies PS, Ueno H, von Furstenberg RJ, Belgrader P, Ziraldo SB, Ordonez H, Henning SJ, Wong MH, Snyder MP, Weissman IL, Hsueh AJ, Mikkelsen TS, Garcia KC, Kuo CJ (2017) Non-equivalence of Wnt and R-spondin ligands during Lgr5(+) intestinal stem-cell self-renewal. Nature 545(7653):238–242

    Article  CAS  PubMed  Google Scholar 

  47. Barker N, van Es JH, Kuipers J, Kujala P, van den Born M, Cozijnsen M, Haegebarth A, Korving J, Begthel H, Peters PJ, Clevers H (2007) Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature 449(7165):1003–1007

    Article  CAS  PubMed  Google Scholar 

  48. Leushacke M, Barker N (2012) Lgr5 and Lgr6 as markers to study adult stem cell roles in self-renewal and cancer. Oncogene 31(25):3009–3022

    Article  CAS  PubMed  Google Scholar 

  49. Sun Y, Jia X, Wu X (2016) High Expressions of Lgr5 and ALDH1 in primary epithelial ovarian cancer correlate with advanced tumor stage and grade as well as poor prognosis of the patients. Gynecol Obstet Invest 81:162–168

    Article  CAS  Google Scholar 

  50. Flesken-Nikitin A, Hwang CI, Cheng CY, Michurina TV, Enikolopov G, Nikitin AY (2013) Ovarian surface epithelium at the junction area contains a cancer-prone stem cell niche. Nature 495(7440):241–245

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Kessler M, Hoffmann K, Brinkmann V, Thieck O, Jackisch S, Toelle B, Berger H, Mollenkopf HJ, Mangler M, Sehouli J, Fotopoulou C, Meyer TF (2015) The Notch and Wnt pathways regulate stemness and differentiation in human fallopian tube organoids. Nat Commun 6:8989

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Schmeler KM, Lu KH (2008) Gynecologic cancers associated with Lynch syndrome/HNPCC. Clin Transl Oncol 10(6):313–317

    Article  CAS  PubMed  Google Scholar 

  53. Pölcher M, Hauptmann S, Fotopoulou C, Schmalfeldt B, Meinhold-Heerlein I, Mustea A, Runnebaum I, Sehouli J (2015) Opportunistic salpingectomies for the prevention of a high-grade serous carcinoma: a statement by the Kommission Ovar of the AGO. Arch Gynecol Obstet 292(1):231–234

    Article  PubMed  Google Scholar 

  54. Kotsopoulos J, Terry KL, Poole EM, Rosner B, Murphy MA, Hecht JL, Crum CP, Missmer SA, Cramer DW, Tworoger SS (2013) Ovarian cancer risk factors by tumor dominance, a surrogate for cell of origin. Int J Cancer 133(3):730–739

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Mungenast F, Thalhammer T (2014) Estrogen biosynthesis and action in ovarian cancer. Front Endocrinol (Lausanne) 5:192

    Google Scholar 

  56. Zhou B, Sun Q, Cong R, Gu H, Tang N, Yang L, Wang B (2008) Hormone replacement therapy and ovarian cancer risk: a meta-analysis. Gynecol Oncol 108(3):641–651

    Article  CAS  PubMed  Google Scholar 

  57. Hernandez E, Rosenshein NB, Bhagavan BS, Parmley TH (1984) Tumor heterogeneity and histopathology in epithelial ovarian cancer. Obstet Gynecol 63(3):330–334

    CAS  PubMed  Google Scholar 

  58. Alizadeh AA, Aranda V, Bardelli A, Blanpain C, Bock C, Borowski C, Caldas C, Califano A, Doherty M, Elsner M, Esteller M, Fitzgerald R, Korbel JO, Lichter P, Mason CE, Navin N, Pe’er D, Polyak K, Roberts CW, Siu L, Snyder A, Stower H, Swanton C, Verhaak RG, Zenklusen JC, Zuber J, Zucman-Rossi J (2015) Toward understanding and exploiting tumor heterogeneity. Nat Med 21(8):846–853

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Merritt MA, Bentink S, Schwede M, Iwanicki MP, Quackenbush J, Woo T, Agoston ES, Reinhardt F, Crum CP, Berkowitz RS, Mok SC, Witt AE, Jones MA, Wang B, Ince TA (2013) Gene expression signature of normal cell-of-origin predicts ovarian tumor outcomes. PLoS One 8(11):e80314

    Article  PubMed  PubMed Central  Google Scholar 

  60. Domcke S, Sinha R, Levine DA, Sander C, Schultz N (2013) Evaluating cell lines as tumour models by comparison of genomic profiles. Nat Commun 4:2126

    Article  PubMed  PubMed Central  Google Scholar 

  61. Ince TA, Sousa AD, Jones MA, Harrell JC, Agoston ES, Krohn M, Selfors LM, Liu W, Chen K, Yong M, Buchwald P, Wang B, Hale KS, Cohick E, Sergent P, Witt A, Kozhekbaeva Z, Gao S, Agoston AT, Merritt MA, Foster R, Rueda BR, Crum CP, Brugge JS, Mills GB (2015) Characterization of twenty-five ovarian tumour cell lines that phenocopy primary tumours. Nat Commun 6:7419

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Kauff ND, Satagopan JM, Robson ME, Scheuer L, Hensley M, Hudis CA, Ellis NA, Boyd J, Borgen PI, Barakat RR, Norton L, Castiel M, Nafa K, Offit K (2002) Risk-reducing salpingo-oophorectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med 346(21):1609–1615

    Article  PubMed  Google Scholar 

  63. Song T, Kim MK, Kim ML, Jung YW, Yun BS, Seong SJ, Kwon SH (2017) Impact of opportunistic salpingectomy on anti-Müllerian hormone in patients undergoing laparoscopic hysterectomy: a multicentre randomised controlled trial. BJOG 124(2):314–320

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. German Cancer Consortium (DKTK), Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany

    Daniel Martin Klotz & Pauline Wimberger

  2. Department of Gynecology and Obstetrics, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

    Daniel Martin Klotz & Pauline Wimberger

  3. National Center for Tumor Diseases (NCT), Partner Site Dresden, Dresden, Germany

    Daniel Martin Klotz & Pauline Wimberger

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Klotz, D.M., Wimberger, P. Cells of origin of ovarian cancer: ovarian surface epithelium or fallopian tube?. Arch Gynecol Obstet 296, 1055–1062 (2017). https://doi.org/10.1007/s00404-017-4529-z

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