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 Cibulskis; Scott 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

doi:https://doi.org/10.1016/j.cell.2015.03.053

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

Research output: Contribution to journal › Article › Academic › peer-review

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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

Original language	English
Pages (from-to)	933-945
Journal	Cell
Volume	161
Issue number	4
DOIs	https://doi.org/10.1016/j.cell.2015.03.053
Publication status	Published - 2015

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https://doi.org/10.1016/j.cell.2015.03.053

Cite this

van de Wetering, M., Francies, H. E., Francis, J. M., Bounova, G., Iorio, F., Pronk, A., van Houdt, W., van Gorp, J., Taylor-Weiner, A., Kester, L., McLaren-Douglas, A., Blokker, J., Jaksani, S., Bartfeld, S., Volckman, R., van Sluis, P., Li, V. S. W., Seepo, S., Sekhar Pedamallu, C., ... Clevers, H. (2015). Prospective derivation of a living organoid biobank of colorectal cancer patients. Cell, 161(4), 933-945. https://doi.org/10.1016/j.cell.2015.03.053

@article{3938784846d64b18ac723b0837cd2151,

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",

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

year = "2015",

doi = "https://doi.org/10.1016/j.cell.2015.03.053",

language = "English",

volume = "161",

pages = "933--945",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

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van de Wetering, M, Francies, HE, Francis, JM, Bounova, G, Iorio, F, Pronk, A, van Houdt, W, van Gorp, J, Taylor-Weiner, A, Kester, L, McLaren-Douglas, A, Blokker, J, Jaksani, S, Bartfeld, S, Volckman, R, van Sluis, P, Li, VSW, Seepo, S, Sekhar Pedamallu, C, Cibulskis, K, Carter, SL, McKenna, A, Lawrence, MS, Lichtenstein, L, Stewart, C, Koster, J , Versteeg, R, van Oudenaarden, A, Saez-Rodriguez, J, Vries, RGJ, Getz, G, Wessels, L, Stratton, MR, McDermott, U, Meyerson, M, Garnett, MJ & Clevers, H 2015, 'Prospective derivation of a living organoid biobank of colorectal cancer patients', Cell, vol. 161, no. 4, pp. 933-945. https://doi.org/10.1016/j.cell.2015.03.053

TY - JOUR

T1 - Prospective derivation of a living organoid biobank of colorectal cancer patients

AU - van de Wetering, Marc

AU - Francies, Hayley E.

AU - Francis, Joshua M.

AU - Bounova, Gergana

AU - Iorio, Francesco

AU - Pronk, Apollo

AU - van Houdt, Winan

AU - van Gorp, Joost

AU - Taylor-Weiner, Amaro

AU - Kester, Lennart

AU - McLaren-Douglas, Anne

AU - Blokker, Joyce

AU - Jaksani, Sridevi

AU - Bartfeld, Sina

AU - Volckman, Richard

AU - van Sluis, Peter

AU - Li, Vivian S. W.

AU - Seepo, Sara

AU - Sekhar Pedamallu, Chandra

AU - Cibulskis, Kristian

AU - Carter, Scott L.

AU - McKenna, Aaron

AU - Lawrence, Michael S.

AU - Lichtenstein, Lee

AU - Stewart, Chip

AU - Koster, Jan

AU - Versteeg, Rogier

AU - van Oudenaarden, Alexander

AU - Saez-Rodriguez, Julio

AU - Vries, Robert G. J.

AU - Getz, Gad

AU - Wessels, Lodewyk

AU - Stratton, Michael R.

AU - McDermott, Ultan

AU - Meyerson, Matthew

AU - Garnett, Mathew J.

AU - Clevers, Hans

PY - 2015

Y1 - 2015

N2 - 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

AB - 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

U2 - https://doi.org/10.1016/j.cell.2015.03.053

DO - https://doi.org/10.1016/j.cell.2015.03.053

M3 - Article

C2 - 25957691

SN - 0092-8674

VL - 161

SP - 933

EP - 945

JO - Cell

JF - Cell

IS - 4

ER -