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Cell. 2015 May 7;161(4):933-45. doi: 10.1016/j.cell.2015.03.053.

Prospective derivation of a living organoid biobank of colorectal cancer patients.

Author information

1
Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW), Cancer Genomics and University Medical Center, 3584 CT Utrecht, the Netherlands; Foundation Hubrecht Organoid Technology (HUB), 3584 CT Utrecht, the Netherlands.
2
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
3
The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
4
Computational Cancer Biology, Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands.
5
European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambridge CB10 1SA, UK.
6
Department of Surgery, Diakonessenhuis, 3582 KE Utrecht, the Netherlands.
7
Department of Pathology, Diakonessenhuis, 3582 KE Utrecht, the Netherlands.
8
The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
9
Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW), Cancer Genomics and University Medical Center, 3584 CT Utrecht, the Netherlands.
10
Department of Oncogenomics, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.
11
Division of Stem Cell Biology and Developmental Genetics, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
12
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK. Electronic address: mg12@sanger.ac.uk.
13
Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW), Cancer Genomics and University Medical Center, 3584 CT Utrecht, the Netherlands; Foundation Hubrecht Organoid Technology (HUB), 3584 CT Utrecht, the Netherlands. Electronic address: h.clevers@hubrecht.eu.

Abstract

In Rspondin-based 3D cultures, Lgr5 stem cells from multiple organs form ever-expanding epithelial organoids that retain their tissue identity. We report the establishment of tumor organoid cultures from 20 consecutive colorectal carcinoma (CRC) patients. For most, organoids were also generated from adjacent normal tissue. Organoids closely recapitulate several properties of the original tumor. The spectrum of genetic changes within the "living biobank" agrees well with previous large-scale mutational analyses of CRC. Gene expression analysis indicates that the major CRC molecular subtypes are represented. Tumor organoids are amenable to high-throughput drug screens allowing detection of gene-drug associations. As an example, a single organoid culture was exquisitely sensitive to Wnt secretion (porcupine) inhibitors and carried a mutation in the negative Wnt feedback regulator RNF43, rather than in APC. Organoid technology may fill the gap between cancer genetics and patient trials, complement cell-line- and xenograft-based drug studies, and allow personalized therapy design. PAPERCLIP.

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PMID:
25957691
DOI:
10.1016/j.cell.2015.03.053
[Indexed for MEDLINE]
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