A Living Biobank of Breast Cancer Organoids Captures Disease Heterogeneity

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A Living Biobank of Breast Cancer Organoids Captures Disease Heterogeneity

Journal Article (2018)

Author(s)

Norman Sachs (Oncode Institute, Foundation Hubrecht Organoid Technology (HUB), University Medical Centre Utrecht, Vertex Pharmaceuticals Inc.)

Joep de Ligt ( University Medical Centre Utrecht, Oncode Institute)

Oded Kopper ( University Medical Centre Utrecht, Oncode Institute)

Ewa Gogola (Nederlands Kanker Instituut - Antoni van Leeuwenhoek ziekenhuis)

Gergana Bounova (Oncode Institute, Nederlands Kanker Instituut - Antoni van Leeuwenhoek ziekenhuis)

Fleur Weeber (Nederlands Kanker Instituut - Antoni van Leeuwenhoek ziekenhuis)

Anjali Vanita Balgobind (Foundation Hubrecht Organoid Technology (HUB), University Medical Centre Utrecht)

Karin Wind ( University Medical Centre Utrecht)

Lodewyk Wessels (TU Delft - Electrical Engineering, Mathematics and Computer Science, Oncode Institute, Nederlands Kanker Instituut - Antoni van Leeuwenhoek ziekenhuis)

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Research Group

Pattern Recognition and Bioinformatics

Breast cancer Organoids Biobank Basal Luminal Precision medicine Triple negative

DOI related publication

https://doi.org/10.1016/j.cell.2017.11.010 Final published version

To reference this document use

https://resolver.tudelft.nl/uuid:a1a387f9-00d3-4e1b-aedb-08e53ec655b0

More Info

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Publication Year

2018

Language

English

Research Group

Pattern Recognition and Bioinformatics

Journal title

Cell

Issue number

1-2

Volume number

172

Pages (from-to)

373-386.e10

Downloads counter

431

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. The heterogeneity of breast cancer subtypes can be captured using organoid cultures that can facilitate drug screens that corroborate with patient responses.