Prospective Derivation of a Living Organoid Biobank of Colorectal Cancer Patients

被引：1997

作者：

van de Wetering, Marc ^{[1
,2
]}

Francies, Hayley E. ^{[3
]}

Francis, Joshua M. ^{[4
,5
,6
]}

Bounova, Gergana ^{[7
]}

Iorio, Francesco ^{[8
]}

Pronk, Apollo ^{[9
]}

van Houdt, Winan ^{[9
]}

van Gorp, Joost ^{[10
]}

Taylor-Weiner, Amaro ^{[4
,5
]}

Kester, Lennart ^{[1
]}

McLaren-Douglas, Anne ^{[3
]}

Blokker, Joyce ^{[1
,2
]}

Jaksani, Sridevi ^{[1
,2
]}

Bartfeld, Sina ^{[1
]}

Volckman, Richard ^{[11
]}

van Sluis, Peter ^{[11
]}

Li, Vivian S. W. ^{[12
]}

Seepo, Sara ^{[4
,5
]}

Pedamallu, Chandra Sekhar ^{[4
,5
,6
]}

Cibulskis, Kristian ^{[4
,5
]}

Carter, Scott L. ^{[4
,5
,6
]}

McKenna, Aaron ^{[4
,5
]}

Lawrence, Michael S. ^{[4
,5
]}

Lichtenstein, Lee ^{[4
,5
]}

Stewart, Chip ^{[5
]}

Koster, Jan ^{[11
]}

Versteeg, Rogier ^{[11
]}

van Oudenaarden, Alexander ^{[1
]}

Saez-Rodriguez, Julio ^{[8
]}

Vries, Robert G. J. ^{[1
,2
]}

Getz, Gad ^{[4
,5
,6
]}

Wessels, Lodewyk ^{[7
]}

Stratton, Michael R. ^{[3
]}

McDermott, Ultan ^{[3
]}

Meyerson, Matthew ^{[4
,5
,6
]}

Garnett, Mathew J. ^{[3
]}

Clevers, Hans ^{[1
,2
]}

机构：

[1] Canc Genom & Univ Med Ctr, Royal Netherlands Acad Arts & Sci KNAW, Hubrecht Inst, NL-3584 CT Utrecht, Netherlands

[2] Fdn Hubrecht Organoid Technol HUB, NL-3584 CT Utrecht, Netherlands

[3] Wellcome Trust Sanger Inst, Hinxton CB10 1SA, Cambs, England

[4] MIT, Broad Inst, Cambridge, MA 02142 USA

[5] Harvard Univ, Cambridge, MA 02142 USA

[6] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[7] Netherlands Canc Inst, Computat Canc Biol, NL-1066 CX Amsterdam, Netherlands

[8] European Bioinformat Inst, European Mol Biol, Cambridge CB10 1SA, England

[9] Diakonessen Hosp, Dept Surg, NL-3582 KE Utrecht, Netherlands

[10] Diakonessen Hosp, Dept Pathol, NL-3582 KE Utrecht, Netherlands

[11] Univ Amsterdam, Acad Med Ctr, Dept Oncogenom, NL-1105 AZ Amsterdam, Netherlands

[12] MRC Natl Inst Med Res, Div Stem Cell Biol & Dev Genet, London NW7 1AA, England

来源：

CELL | 2015年 / 161卷 / 04期

关键词：

SMALL-INTESTINE; DRUG-SENSITIVITY; WNT RECEPTORS; COLON-CANCER; STEM-CELLS; GENE; LGR5; EPITHELIUM; MUTATIONS; GENOME;

D O I：

10.1016/j.cell.2015.03.053

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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.

引用

页码：933 / 945

页数：13

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