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. 2018 Jan 11;172(1-2):373-386.e10.
doi: 10.1016/j.cell.2017.11.010. Epub 2017 Dec 7.

A Living Biobank of Breast Cancer Organoids Captures Disease Heterogeneity

Norman Sachs  1 , Joep de Ligt  2 , Oded Kopper  3 , Ewa Gogola  4 , Gergana Bounova  5 , Fleur Weeber  6 , Anjali Vanita Balgobind  7 , Karin Wind  8 , Ana Gracanin  8 , Harry Begthel  8 , Jeroen Korving  8 , Ruben van Boxtel  2 , Alexandra Alves Duarte  4 , Daphne Lelieveld  9 , Arne van Hoeck  2 , Robert Frans Ernst  2 , Francis Blokzijl  2 , Isaac Johannes Nijman  2 , Marlous Hoogstraat  10 , Marieke van de Ven  11 , David Anthony Egan  9 , Vittoria Zinzalla  12 , Jurgen Moll  12 , Sylvia Fernandez Boj  13 , Emile Eugene Voest  6 , Lodewyk Wessels  14 , Paul Joannes van Diest  15 , Sven Rottenberg  16 , Robert Gerhardus Jacob Vries  13 , Edwin Cuppen  2 , Hans Clevers  17
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Free article

A Living Biobank of Breast Cancer Organoids Captures Disease Heterogeneity

Norman Sachs et al. Cell. .
Free 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 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.

Keywords: basal; biobank; breast cancer; luminal; organoids; precision medicine; triple negative.

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