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
Hauptverfasser: 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
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 11.01.2018
Schlagworte:
Animals
Antineoplastic Agents - pharmacology
Breast Neoplasms - genetics
Breast Neoplasms - pathology
Cells, Cultured
Drug Screening Assays, Antitumor - methods
Female
Genetic Heterogeneity
Humans
Mice
Mice, Nude
Organoids - drug effects
Organoids - pathology
Precision Medicine - methods
Tissue Banks
organoids
triple negative
breast cancer
precision medicine
basal
biobank
luminal
ISSN:1097-4172, 1097-4172
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Zusammenfassung: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.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1097-4172
1097-4172
DOI:10.1016/j.cell.2017.11.010