A Living Biobank of Breast Cancer Organoids Captures Disease Heterogeneity
Sachs, Norman; de Ligt, Joep; Kopper, Oded; Gogola, Ewa; Bounova, Gergana; Weeber, Fleur; Balgobind, Anjali Vanita; Wind, Karin; Gracanin, Ana; Begthel, Harry; Korving, Jeroen; van Boxtel, Ruben; Duarte, Alexandra Alves; Lelieveld, Daphne; van Hoeck, Arne; Ernst, Robert Frans; Blokzijl, Francis; Nijman, Isaac Johannes; Hoogstraat, Marlous; van de Ven, Marieke; Egan, David Anthony; Zinzalla, Vittoria; Moll, Jurgen; Boj, Sylvia Fernandez; Voest, Emile Eugene; Wessels, Lodewyk; van Diest, Paul Joannes; Rottenberg, Sven; Vries, Robert Gerhardus Jacob; Cuppen, Edwin; Clevers, Hans
(2018) Cell, volume 172, issue 1-2, pp. 373 - 386.e10
(Article)
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
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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.
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Author keywords: basal, biobank, breast cancer, luminal, organoids, precision medicine, triple negative, Biochemistry, Genetics and Molecular Biology(all)
ISSN: 0092-8674
Note: Copyright © 2017 Elsevier Inc. All rights reserved.
(Publisher version, Peer reviewed)