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A Living Biobank of Breast Cancer Organoids Captures Disease Heterogeneity
Open accessAbstract
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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Metadata
- Authors
- Sachs, N., de Ligt, J., Kopper, O., Gogola, E., Bounova, G., Weeber, F., Balgobind, A. V., Wind, K., Gracanin, A., Begthel, H., Korving, J., van Boxtel, R., Duarte, A. A., Lelieveld, D., van Hoeck, A., Ernst, R. F., Blokzijl, F., Nijman, I. J., Hoogstraat, M., van de Ven, M., Egan, D. A., Zinzalla, V., Moll, J., Boj, S. F., Voest, E. E., Wessels, L., van Diest, P. J., Rottenberg, S., Vries, R. G. J., Cuppen, E., & Clevers, H.
- Affiliations
- Royal Netherlands Academy of Arts and Sciences (NL)
- The Netherlands Cancer Institute (NL)
- University Medical Center Utrecht (NL)
- Utrecht University (NL)
- Boehringer Ingelheim (Austria) (AT)
- Oncode Institute (NL)
- University of Bern (CH)
- Corresponding author
- Clevers, Hans
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2018-01
- Volume
- 172
- Issue
- 1-2
- Pages
- 373-386.e10
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2773981699
- Cited by
- 1,973
- References
- 79
- Citations by year
- 2026: 219 · 2025: 240 · 2024: 288 · 2023: 251 · 2022: 274 · 2021: 259 · 2020: 238 · 2019: 127 · 2018: 74
- FWCI
- 53.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Bern Open Repository and Information System (University of Bern) (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion)
- Funders
- MKMD (114021012)
- Netherlands Organization for Scientific Research (91615182, 114021012)
- Stand Up to Cancer International Translational Cancer Research Grant
- Stichting Vrienden van Hubrecht (2012.010)
- Cancer Genomic Center (2014-186)
- Boehringer-Ingelheim RCV GmbH & Co KG (141947)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Keywords
- breast cancer, organoid biobank, tumor heterogeneity, metastatic breast cancer, long-term organoid culture, copy number variation, gene expression subtypes, hormone receptor status, HER2 status, in vitro drug testing, xenotransplantation
- MeSH terms
- Animals, Antineoplastic Agents, Breast Neoplasms, Cells, Cultured, Drug Screening Assays, Antitumor, Female, Humans, Mice, Nude, Organoids, Tissue Banks, Genetic Heterogeneity, Mice, Precision Medicine
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