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P119 An organoid platform for ovarian cancer captures intra- and interpatient heterogeneity
  1. O Kopper1,2,
  2. CJ de Witte2,3,
  3. K Lõhmussaar1,2,
  4. J Espejo Valle-Inclan2,3,
  5. N Hami2,4,
  6. L Kester1,2,
  7. AV Balgobind1,2,
  8. J Korving1,2,
  9. N Proost5,
  10. H Begthel1,2,
  11. LM van Wijk6,
  12. SA Revilla1,2,
  13. R Theeuwsen5,
  14. M van de Ven5,
  15. MJ van Roosmalen3,
  16. B Ponsioen2,4,
  17. VWH Ho7,
  18. BG Neel7,8,
  19. T Bosse9,
  20. KN Gaarenstroom9,
  21. H Vrieling6,
  22. MPG Vreeswijk6,
  23. PJ van Diest10,
  24. PO Witteveen11,
  25. T Jonges10,
  26. JL Bos2,4,
  27. A van Oudenaarden1,2,
  28. RP Zweemer12,
  29. HJG Snippert2,4,
  30. WP Kloosterman3 and
  31. H Clevers1,2,13
  1. 1Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and UMC Utrecht
  2. 2Oncode Institute
  3. 3Center for Molecular Medicine
  4. 4Molecular Cancer Research, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht
  5. 5Preclinical Intervention Unit of the Mouse Clinic for Cancer and Ageing (MCCA), Netherlands Cancer Institute, Amsterdam
  6. 6Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
  7. 7Princess Margaret Cancer Center, University Health Network, Toronto, ON, Canada
  8. 8Perlmutter Cancer Center, NYU Langone Health, New York, NY, USA
  9. 9Department of Pathology, Leiden University Medical Center, Leiden
  10. 10Department of Pathology
  11. 11Department of Medical Oncology, Cancer Center
  12. 12Department of Gynaecological Oncology, Cancer Center, University Medical Center Utrecht, Utrecht University
  13. 13The Netherlands Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands


Introduction/Background Ovarian cancer (OC) is a heterogeneous disease usually diagnosed at a late stage. Experimental in vitro models that faithfully capture the hallmarks and tumour heterogeneity of OC are limited and hard to establish.

Methodology We present a protocol that enables efficient derivation and long-term expansion of OC organoids.

Results Utilizing this protocol, we have established 56 organoid lines from 32 patients, representing all main subtypes of OC. OC organoids recapitulate histological and genomic features of the pertinent lesion from which they were derived, illustrating intra- and interpatient heterogeneity, and can be genetically modified. We show that OC organoids can be used for drug-screening assays and capture different tumour subtype responses to the gold standard platinum-based chemotherapy, including acquisition of chemoresistance in recurrent disease. Finally, OC organoids can be xenografted, enabling in vivo drug-sensitivity assays.

Conclusion Taken together, this demonstrates their potential application for research and personalized medicine.

Disclosure No competing interests. Applicable funding sources: EIF | Stand Up To Cancer (SU2C) [Clevers, Kopper, Balgobind, Begthel] KWF Kankerbestrijding (Dutch Cancer Society) - UU2015-7743 [de Witte, van Roosmalen, Witteveen, Zweemer, Kloosterman] Gieskes Strijbis Foundation (1816199) [Clevers, Witteveen, Kloosterman, Zweemer, Lõhmussaar, Espejo Valle-Inclan, Hami, Bos, Snippert] Published in Nature Medicine. April 2019.

Abstract P119 Figure 1

Ovarian cancer organoid biobankA. schematic of OC organoid. B. An overview of the number of established OC organoid lines according to their subtype distribution. MBT = Mucinous tumour, SBT = serous borderline tumour, CCC = clear cell carcinoma, END = endometrioid carcinoma, MC = mucinous carcinoma, LGS = low grade serous carcinoma, HGS = high grade serous carcinoma. C. In vitro drug sensitivity assay. Representative dose-response curves of HGS and LGS organoid lines treated with carboplatin/paclitaxel. Organoid line derived from recurrent disease (HGS-1-R3) shows acquired resistance. Dots represent the mean of technical duplicates. Error bars represent s.e.m. of technical duplicates.

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