title: Prospective derivation of a living organoid biobank of colorectal cancer patients.
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.
authors.affiliation: 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.
authors.forename: Marc
authors.initials: M
authors.lastname: van de Wetering
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
authors.forename: Hayley E
authors.initials: HE
authors.lastname: Francies
authors.affiliation: The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Francis
authors.affiliation: Computational Cancer Biology, Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands.
authors.forename: Gergana
authors.initials: G
authors.lastname: Bounova
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambridge CB10 1SA, UK.
authors.forename: Francesco
authors.initials: F
authors.lastname: Iorio
authors.affiliation: Department of Surgery, Diakonessenhuis, 3582 KE Utrecht, the Netherlands.
authors.forename: Apollo
authors.initials: A
authors.lastname: Pronk
authors.affiliation: Department of Surgery, Diakonessenhuis, 3582 KE Utrecht, the Netherlands.
authors.forename: Winan
authors.initials: W
authors.lastname: van Houdt
authors.affiliation: Department of Pathology, Diakonessenhuis, 3582 KE Utrecht, the Netherlands.
authors.forename: Joost
authors.initials: J
authors.lastname: van Gorp
authors.affiliation: The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
authors.forename: Amaro
authors.initials: A
authors.lastname: Taylor-Weiner
authors.affiliation: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW), Cancer Genomics and University Medical Center, 3584 CT Utrecht, the Netherlands.
authors.forename: Lennart
authors.initials: L
authors.lastname: Kester
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
authors.forename: Anne
authors.initials: A
authors.lastname: McLaren-Douglas
authors.affiliation: 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.
authors.forename: Joyce
authors.initials: J
authors.lastname: Blokker
authors.affiliation: 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.
authors.forename: Sridevi
authors.initials: S
authors.lastname: Jaksani
authors.affiliation: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW), Cancer Genomics and University Medical Center, 3584 CT Utrecht, the Netherlands.
authors.forename: Sina
authors.initials: S
authors.lastname: Bartfeld
authors.affiliation: Department of Oncogenomics, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.
authors.forename: Richard
authors.initials: R
authors.lastname: Volckman
authors.affiliation: Department of Oncogenomics, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: van Sluis
authors.affiliation: Division of Stem Cell Biology and Developmental Genetics, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
authors.forename: Vivian S W
authors.initials: VS
authors.lastname: Li
authors.affiliation: The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Seepo
authors.affiliation: The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
authors.forename: Chandra
authors.initials: C
authors.lastname: Sekhar Pedamallu
authors.affiliation: The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
authors.forename: Kristian
authors.initials: K
authors.lastname: Cibulskis
authors.affiliation: The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
authors.forename: Scott L
authors.initials: SL
authors.lastname: Carter
authors.affiliation: The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: McKenna
authors.affiliation: The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Lawrence
authors.affiliation: The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
authors.forename: Lee
authors.initials: L
authors.lastname: Lichtenstein
authors.affiliation: The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
authors.forename: Chip
authors.initials: C
authors.lastname: Stewart
authors.affiliation: Department of Oncogenomics, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Koster
authors.affiliation: Department of Oncogenomics, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.
authors.forename: Rogier
authors.initials: R
authors.lastname: Versteeg
authors.affiliation: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW), Cancer Genomics and University Medical Center, 3584 CT Utrecht, the Netherlands.
authors.forename: Alexander
authors.initials: A
authors.lastname: van Oudenaarden
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambridge CB10 1SA, UK.
authors.forename: Julio
authors.initials: J
authors.lastname: Saez-Rodriguez
authors.affiliation: 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.
authors.forename: Robert G J
authors.initials: RG
authors.lastname: Vries
authors.affiliation: The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
authors.forename: Gad
authors.initials: G
authors.lastname: Getz
authors.affiliation: Computational Cancer Biology, Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands.
authors.forename: Lodewyk
authors.initials: L
authors.lastname: Wessels
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Stratton
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
authors.forename: Ultan
authors.initials: U
authors.lastname: McDermott
authors.affiliation: The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Meyerson
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK. Electronic address: mg12@sanger.ac.uk.
authors.forename: Mathew J
authors.initials: MJ
authors.lastname: Garnett
authors.affiliation: 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.
authors.forename: Hans
authors.initials: H
authors.lastname: Clevers
mesh_terms: D018070:Biological Specimen Banks; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D006801:Humans; D015513:Oncogene Proteins / Q000378:metabolism; D009924:Organ Culture Techniques; D009940:Organoids / Q000187:drug effects; D057285:Precision Medicine; D044767:Ubiquitin-Protein Ligases
chemical_list: D004268:DNA-Binding Proteins; D015513:Oncogene Proteins; C496945:RNF43 protein, human; D044767:Ubiquitin-Protein Ligases