A Living Biobank of Breast Cancer Organoids Captures Disease Heterogeneity
| Autor: | Harry Begthel, Fleur Weeber, Lodewyk F. A. Wessels, Marieke van der Ven, Robert G.J. Vries, Jeroen Korving, Karin Wind, Alexandra A. Duarte, Robert F Ernst, Anjali Vanita Balgobind, Isaac J. Nijman, Ruben van Boxtel, Sylvia F. Boj, Edwin Cuppen, Gergana Bounova, Sven Rottenberg, Arne Van Hoeck, Paul J. van Diest, Francis Blokzijl, Daphne Lelieveld, David A. Egan, Vittoria Zinzalla, Ana Gracanin, Emile E. Voest, Joep de Ligt, Oded Kopper, Hans Clevers, Marlous Hoogstraat, Ewa Gogola, Norman Sachs, Jürgen Moll |
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| Přispěvatelé: | Hubrecht Institute for Developmental Biology and Stem Cell Research |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty precision medicine Disease Biology Biochemistry General Biochemistry Genetics and Molecular Biology triple negative 03 medical and health sciences Breast cancer breast cancer basal medicine Organoid Journal Article Copy-number variation 610 Medicine & health organoids luminal 630 Agriculture Genetic heterogeneity Biochemistry Genetics and Molecular Biology(all) medicine.disease Biobank biobank 030104 developmental biology Drug development Cancer research 570 Life sciences biology Histopathology Genetics and Molecular Biology(all) |
| Zdroj: | Cell. Elsevier B.V. Cell, 172(1-2), 373. Cell Press |
| ISSN: | 0092-8674 |
| Popis: | 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. The heterogeneity of breast cancer subtypes can be captured using organoid cultures that can facilitate drug screens that corroborate with patient responses. |
| Databáze: | OpenAIRE |
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