Implementing cell-free DNA of pancreatic cancer patient-derived organoids for personalized oncology

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Zahra Dantes - , Technical University of Munich (Author)
  • Hsi-Yu Yen - , Technical University of Munich (Author)
  • Nicole Pfarr - , Technical University of Munich (Author)
  • Christof Winter - , Technical University of Munich, Helmholtz-Zentrum Dresden-Rossendorf (Author)
  • Katja Steiger - , Technical University of Munich (Author)
  • Alexander Muckenhuber - , Technical University of Munich (Author)
  • Alexander Hennig - , Chair of Systems Biology and Genetics, Dresden University of Technology, University Hospital Carl Gustav Carus Dresden (Author)
  • Sebastian Lange - , Center for International Studies, Technical University of Munich, Klin & Poliklin Innere Med 2 (Author)
  • Thomas Engleitner - , Technical University of Munich (Author)
  • Rupert Oellinger - , Technical University of Munich (Author)
  • Roman Maresch - , Technical University of Munich (Author)
  • Felix Orben - , Technical University of Munich (Author)
  • Irina Heid - , Technical University of Munich (Author)
  • Georgios Kaissis - , Technical University of Munich (Author)
  • Kuangyu Shi - , Technical University of Munich (Author)
  • Geoffrey Topping - , Technical University of Munich (Author)
  • Fabian Stoegbauer - , Technical University of Munich (Author)
  • Matthias Wirth - , Free University of Berlin (Author)
  • Katja Peschke - , Technical University of Munich (Author)
  • Aristeidis Papargyriou - , Technical University of Munich (Author)
  • Massoud Rezaee-Oghazi - , Technical University of Munich (Author)
  • Karin Feldmann - , Technical University of Munich (Author)
  • Arlett P. G. Schaefer - , Technical University of Munich (Author)
  • Raphela Ranjan - , Technical University of Munich (Author)
  • Clara Lubeseder-Martellato - , Technical University of Munich (Author)
  • Daniel E. Stange - , German Center for Neurodegenerative Diseases, Dresden site (Partner: DZNE of the Helmholtz Association), German Cancer Consortium (Partner: DKTK, DKFZ), Department of Visceral, Thoracic and Vascular Surgery, Dresden University of Technology, University Hospital Carl Gustav Carus Dresden (Author)
  • Thilo Welsch - , Helmholtz-Zentrum Dresden-Rossendorf, Dresden University of Technology (Author)
  • Marc Martignoni - , Technical University of Munich (Author)
  • Gueralp O. Ceyhan - , Technical University of Munich (Author)
  • Helmut Friess - , Technical University of Munich (Author)
  • Alexander Herner - , Technical University of Munich (Author)
  • Lucia Liotta - , Technical University of Munich (Author)
  • Matthias Treiber - , Technical University of Munich (Author)
  • Guido von Figura - , Technical University of Munich (Author)
  • Mohamed Abdelhafez - , Technical University of Munich (Author)
  • Peter Klare - , Technical University of Munich (Author)
  • Christoph Schlag - , Technical University of Munich (Author)
  • Hana Alguel - , Technical University of Munich (Author)
  • Jens Siveke - , Helmholtz-Zentrum Dresden-Rossendorf, University of Duisburg-Essen (Author)
  • Rickmer Braren - , Helmholtz-Zentrum Dresden-Rossendorf, Dresden University of Technology (Author)
  • Gregor Weirich - , Technical University of Munich (Author)
  • Wilko Weichert - , Technical University of Munich, Helmholtz-Zentrum Dresden-Rossendorf (Author)
  • Dieter Saur - , Technical University of Munich, Helmholtz-Zentrum Dresden-Rossendorf (Author)
  • Roland Rad - , Technical University of Munich, Helmholtz-Zentrum Dresden-Rossendorf (Author)
  • Roland M. Schmid - , Technical University of Munich (Author)
  • Guenter Schneider - , Technical University of Munich, Helmholtz-Zentrum Dresden-Rossendorf (Author)
  • Maximilian Reichert - , Technical University of Munich, Helmholtz-Zentrum Dresden-Rossendorf (Author)

Abstract

One of the major challenges in using pancreatic cancer patient-derived organoids (PDOs) in precision oncology is the time from biopsy to functional characterization. This is particularly true for endoscopic ultrasound-guided fine-needle aspiration biopsies, typically resulting in specimens with limited tumor cell yield. Here, we tested conditioned media of individual PDOs for cell-free DNA to detect driver mutations already early on during the expansion process to accelerate the genetic characterization of PDOs as well as subsequent functional testing. Importantly, genetic alterations detected in the PDO supernatant, collected as early as 72 hours after biopsy, recapitulate the mutational profile of the primary tumor, indicating suitability of this approach to subject PDOs to drug testing in a reduced time frame. In addition, we demonstrated that this workflow was practicable, even in patients for whom the amount of tumor material was not sufficient for molecular characterization by established means. Together, our findings demonstrate that generating PDOs from very limited biopsy material permits molecular profiling and drug testing. With our approach, this can be achieved in a rapid and feasible fashion with broad implications in clinical practice.

Details

Original languageEnglish
Number of pages12
JournalJCI insight
Publication statusPublished - 6 Aug 2020
Peer-reviewedYes

External IDs

PubMed 32614802
Scopus 85089206125

Keywords

Keywords

  • Ductal adenocarcinoma, Breast-cancer, Stem-cell, Tumor, Subtypes, Biobank, Models