A Living Biobank of Breast Cancer Organoids Captures Disease Heterogeneity
Breast cancer (BC) comprises multiple distinct subtypes that differ genetically, pathologically, and clinically. Here, we describe a robust protocol for long-term culturing of human mammary epithelial organoids. Using this protocol, >100 primary and metastatic BC organoid lines were generated, br...
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| Veröffentlicht in: | Cell Jg. 172; H. 1-2; S. 373 |
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| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Journal Article |
| Sprache: | Englisch |
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United States
11.01.2018
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| ISSN: | 1097-4172, 1097-4172 |
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| Abstract | Breast cancer (BC) comprises multiple distinct subtypes that differ genetically, pathologically, and clinically. Here, we describe a robust protocol for long-term culturing of human mammary epithelial organoids. Using this protocol, >100 primary and metastatic BC organoid lines were generated, broadly recapitulating the diversity of the disease. BC organoid morphologies typically matched the histopathology, hormone receptor status, and HER2 status of the original tumor. DNA copy number variations as well as sequence changes were consistent within tumor-organoid pairs and largely retained even after extended passaging. BC organoids furthermore populated all major gene-expression-based classification groups and allowed in vitro drug screens that were consistent with in vivo xeno-transplantations and patient response. This study describes a representative collection of well-characterized BC organoids available for cancer research and drug development, as well as a strategy to assess in vitro drug response in a personalized fashion. |
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| AbstractList | Breast cancer (BC) comprises multiple distinct subtypes that differ genetically, pathologically, and clinically. Here, we describe a robust protocol for long-term culturing of human mammary epithelial organoids. Using this protocol, >100 primary and metastatic BC organoid lines were generated, broadly recapitulating the diversity of the disease. BC organoid morphologies typically matched the histopathology, hormone receptor status, and HER2 status of the original tumor. DNA copy number variations as well as sequence changes were consistent within tumor-organoid pairs and largely retained even after extended passaging. BC organoids furthermore populated all major gene-expression-based classification groups and allowed in vitro drug screens that were consistent with in vivo xeno-transplantations and patient response. This study describes a representative collection of well-characterized BC organoids available for cancer research and drug development, as well as a strategy to assess in vitro drug response in a personalized fashion.Breast cancer (BC) comprises multiple distinct subtypes that differ genetically, pathologically, and clinically. Here, we describe a robust protocol for long-term culturing of human mammary epithelial organoids. Using this protocol, >100 primary and metastatic BC organoid lines were generated, broadly recapitulating the diversity of the disease. BC organoid morphologies typically matched the histopathology, hormone receptor status, and HER2 status of the original tumor. DNA copy number variations as well as sequence changes were consistent within tumor-organoid pairs and largely retained even after extended passaging. BC organoids furthermore populated all major gene-expression-based classification groups and allowed in vitro drug screens that were consistent with in vivo xeno-transplantations and patient response. This study describes a representative collection of well-characterized BC organoids available for cancer research and drug development, as well as a strategy to assess in vitro drug response in a personalized fashion. Breast cancer (BC) comprises multiple distinct subtypes that differ genetically, pathologically, and clinically. Here, we describe a robust protocol for long-term culturing of human mammary epithelial organoids. Using this protocol, >100 primary and metastatic BC organoid lines were generated, broadly recapitulating the diversity of the disease. BC organoid morphologies typically matched the histopathology, hormone receptor status, and HER2 status of the original tumor. DNA copy number variations as well as sequence changes were consistent within tumor-organoid pairs and largely retained even after extended passaging. BC organoids furthermore populated all major gene-expression-based classification groups and allowed in vitro drug screens that were consistent with in vivo xeno-transplantations and patient response. This study describes a representative collection of well-characterized BC organoids available for cancer research and drug development, as well as a strategy to assess in vitro drug response in a personalized fashion. |
| Author | Clevers, Hans Rottenberg, Sven Gogola, Ewa Weeber, Fleur van Boxtel, Ruben van Diest, Paul Joannes Sachs, Norman Begthel, Harry Ernst, Robert Frans Nijman, Isaac Johannes Egan, David Anthony Korving, Jeroen Kopper, Oded Boj, Sylvia Fernandez Balgobind, Anjali Vanita van Hoeck, Arne Zinzalla, Vittoria Voest, Emile Eugene Wessels, Lodewyk Blokzijl, Francis van de Ven, Marieke Moll, Jurgen de Ligt, Joep Duarte, Alexandra Alves Gracanin, Ana Lelieveld, Daphne Vries, Robert Gerhardus Jacob Wind, Karin Bounova, Gergana Hoogstraat, Marlous Cuppen, Edwin |
| Author_xml | – sequence: 1 givenname: Norman surname: Sachs fullname: Sachs, Norman organization: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands; Foundation Hubrecht Organoid Technology (HUB), Yalelaan 62, 3584 CM Utrecht, the Netherlands; Cancer Genomics Netherlands, Oncode Institute, 3584 CG Utrecht, the Netherlands – sequence: 2 givenname: Joep surname: de Ligt fullname: de Ligt, Joep organization: Center for Molecular Medicine, Department of Genetics, University Medical Center Utrecht, Utrecht University, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands; Cancer Genomics Netherlands, Oncode Institute, 3584 CG Utrecht, the Netherlands – sequence: 3 givenname: Oded surname: Kopper fullname: Kopper, Oded organization: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands; Cancer Genomics Netherlands, Oncode Institute, 3584 CG Utrecht, the Netherlands – sequence: 4 givenname: Ewa surname: Gogola fullname: Gogola, Ewa organization: Division of Molecular Pathology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands – sequence: 5 givenname: Gergana surname: Bounova fullname: Bounova, Gergana organization: Division of Molecular Carcinogenesis, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands; Cancer Genomics Netherlands, Oncode Institute, 3584 CG Utrecht, the Netherlands – sequence: 6 givenname: Fleur surname: Weeber fullname: Weeber, Fleur organization: Division of Molecular Oncology and Immunology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands – sequence: 7 givenname: Anjali Vanita surname: Balgobind fullname: Balgobind, Anjali Vanita organization: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands; Foundation Hubrecht Organoid Technology (HUB), Yalelaan 62, 3584 CM Utrecht, the Netherlands – sequence: 8 givenname: Karin surname: Wind fullname: Wind, Karin organization: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands – sequence: 9 givenname: Ana surname: Gracanin fullname: Gracanin, Ana organization: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands – sequence: 10 givenname: Harry surname: Begthel fullname: Begthel, Harry organization: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands – sequence: 11 givenname: Jeroen surname: Korving fullname: Korving, Jeroen organization: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands – sequence: 12 givenname: Ruben surname: van Boxtel fullname: van Boxtel, Ruben organization: Center for Molecular Medicine, Department of Genetics, University Medical Center Utrecht, Utrecht University, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands; Cancer Genomics Netherlands, Oncode Institute, 3584 CG Utrecht, the Netherlands – sequence: 13 givenname: Alexandra Alves surname: Duarte fullname: Duarte, Alexandra Alves organization: Division of Molecular Pathology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands – sequence: 14 givenname: Daphne surname: Lelieveld fullname: Lelieveld, Daphne organization: Cell Screening Core, Department of Cell Biology, Center for Molecular Medicine, University Medical Center, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands – sequence: 15 givenname: Arne surname: van Hoeck fullname: van Hoeck, Arne organization: Center for Molecular Medicine, Department of Genetics, University Medical Center Utrecht, Utrecht University, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands; Cancer Genomics Netherlands, Oncode Institute, 3584 CG Utrecht, the Netherlands – sequence: 16 givenname: Robert Frans surname: Ernst fullname: Ernst, Robert Frans organization: Center for Molecular Medicine, Department of Genetics, University Medical Center Utrecht, Utrecht University, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands; Cancer Genomics Netherlands, Oncode Institute, 3584 CG Utrecht, the Netherlands – sequence: 17 givenname: Francis surname: Blokzijl fullname: Blokzijl, Francis organization: Center for Molecular Medicine, Department of Genetics, University Medical Center Utrecht, Utrecht University, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands; Cancer Genomics Netherlands, Oncode Institute, 3584 CG Utrecht, the Netherlands – sequence: 18 givenname: Isaac Johannes surname: Nijman fullname: Nijman, Isaac Johannes organization: Center for Molecular Medicine, Department of Genetics, University Medical Center Utrecht, Utrecht University, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands; Cancer Genomics Netherlands, Oncode Institute, 3584 CG Utrecht, the Netherlands – sequence: 19 givenname: Marlous surname: Hoogstraat fullname: Hoogstraat, Marlous organization: Division of Molecular Carcinogenesis, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands – sequence: 20 givenname: Marieke surname: van de Ven fullname: van de Ven, Marieke organization: Mouse Clinic for Cancer and Aging (MCCA), Preclinical Intervention Unit, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands – sequence: 21 givenname: David Anthony surname: Egan fullname: Egan, David Anthony organization: Cell Screening Core, Department of Cell Biology, Center for Molecular Medicine, University Medical Center, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands – sequence: 22 givenname: Vittoria surname: Zinzalla fullname: Zinzalla, Vittoria organization: Pharmacology and Translational Research, Boehringer Ingelheim RCV GmbH & Co KG, Dr. Boehringer-Gasse 5-11, 1121 Vienna, Austria – sequence: 23 givenname: Jurgen surname: Moll fullname: Moll, Jurgen organization: Pharmacology and Translational Research, Boehringer Ingelheim RCV GmbH & Co KG, Dr. Boehringer-Gasse 5-11, 1121 Vienna, Austria – sequence: 24 givenname: Sylvia Fernandez surname: Boj fullname: Boj, Sylvia Fernandez organization: Foundation Hubrecht Organoid Technology (HUB), Yalelaan 62, 3584 CM Utrecht, the Netherlands; Cancer Genomics Netherlands, Oncode Institute, 3584 CG Utrecht, the Netherlands – sequence: 25 givenname: Emile Eugene surname: Voest fullname: Voest, Emile Eugene organization: Division of Molecular Oncology and Immunology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands – sequence: 26 givenname: Lodewyk surname: Wessels fullname: Wessels, Lodewyk organization: Division of Molecular Pathology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands; Cancer Genomics Netherlands, Oncode Institute, 3584 CG Utrecht, the Netherlands; Faculty of EEMCS, Delft University of Technology, Delft, the Netherlands – sequence: 27 givenname: Paul Joannes surname: van Diest fullname: van Diest, Paul Joannes organization: Department of Pathology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands – sequence: 28 givenname: Sven surname: Rottenberg fullname: Rottenberg, Sven organization: Division of Molecular Pathology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands; Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, Länggassstrasse 122, 3012 Bern, Switzerland – sequence: 29 givenname: Robert Gerhardus Jacob surname: Vries fullname: Vries, Robert Gerhardus Jacob organization: Foundation Hubrecht Organoid Technology (HUB), Yalelaan 62, 3584 CM Utrecht, the Netherlands; Cancer Genomics Netherlands, Oncode Institute, 3584 CG Utrecht, the Netherlands – sequence: 30 givenname: Edwin surname: Cuppen fullname: Cuppen, Edwin organization: Center for Molecular Medicine, Department of Genetics, University Medical Center Utrecht, Utrecht University, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands; Cancer Genomics Netherlands, Oncode Institute, 3584 CG Utrecht, the Netherlands – sequence: 31 givenname: Hans surname: Clevers fullname: Clevers, Hans email: h.clevers@hubrecht.eu organization: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands; Cancer Genomics Netherlands, Oncode Institute, 3584 CG Utrecht, the Netherlands. Electronic address: h.clevers@hubrecht.eu |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/29224780$$D View this record in MEDLINE/PubMed |
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| Keywords | organoids triple negative breast cancer precision medicine basal biobank luminal |
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| Title | A Living Biobank of Breast Cancer Organoids Captures Disease Heterogeneity |
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