Prospective derivation of a living organoid biobank of colorectal cancer patients

Marc van de Wetering, Hayley E Francies, Joshua M Francis, Gergana Bounova, Francesco Iorio, Apollo Pronk, Winan van Houdt, Joost van Gorp, Amaro Taylor-Weiner, Lennart Kester, Anne McLaren-Douglas, Joyce Blokker, Sridevi Jaksani, Sina Bartfeld, Richard Volckman, Peter van Sluis, Vivian S W Li, Sara Seepo, Chandra Sekhar Pedamallu, Kristian CibulskisScott L Carter, Aaron McKenna, Michael S Lawrence, Lee Lichtenstein, Chip Stewart, Jan Koster, Rogier Versteeg, Alexander van Oudenaarden, Julio Saez-Rodriguez, Robert G J Vries, Gad Getz, Lodewyk Wessels, Michael R Stratton, Ultan McDermott, Matthew Meyerson, Mathew J Garnett, Hans Clevers

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgaveArtikelWetenschappelijkpeer review

Samenvatting

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.

Originele taal-2Engels
Pagina's (van-tot)933-45
Aantal pagina's13
TijdschriftCell
Volume161
Nummer van het tijdschrift4
DOI's
StatusGepubliceerd - 07 mei 2015

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