TY - JOUR KW - Animals KW - Antineoplastic Agents KW - Breast Neoplasms KW - Cells, Cultured KW - Drug Screening Assays, Antitumor KW - Female KW - Genetic Heterogeneity KW - Humans KW - Mice KW - Mice, Nude KW - organoids KW - Precision Medicine KW - Tissue Banks KW - basal KW - biobank KW - Breast cancer KW - luminal KW - organoids KW - Precision Medicine KW - triple negative AU - Norman Sachs AU - Joep de Ligt AU - Oded Kopper AU - Ewa Gogola AU - Gergana Bounova AU - Fleur Weeber AU - Anjali Vanita Balgobind AU - Karin Wind AU - Ana Gracanin AU - Harry Begthel AU - Jeroen Korving AU - Ruben van Boxtel AU - Alexandra Alves Duarte AU - Daphne Lelieveld AU - Arne van Hoeck AU - Robert Frans Ernst AU - Francis Blokzijl AU - Isaac Johannes Nijman AU - Marlous Hoogstraat AU - Marieke van de Ven AU - David Anthony Egan AU - Vittoria Zinzalla AU - Jurgen Moll AU - Sylvia Fernandez Boj AU - Emile Eugene Voest AU - Lodewyk Wessels AU - Paul Joannes van Diest AU - Sven Rottenberg AU - Robert Gerhardus Jacob Vries AU - Edwin Cuppen AU - Hans Clevers AB - 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. BT - Cell DA - 2018-01-11 DO - 10.1016/j.cell.2017.11.010 IS - 1-2 LA - eng N2 - 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. PY - 2018 SP - 373 EP - 386.e10 T2 - Cell TI - A Living Biobank of Breast Cancer Organoids Captures Disease Heterogeneity VL - 172 SN - 1097-4172 ER -