A Living Biobank of Breast Cancer Organoids Captures Disease Heterogeneity

被引：1390

作者：

Sachs, Norman ^{[1
,2
,3
,12
,15
]}

de Ligt, Joep ^{[4
,12
]}

Kopper, Oded ^{[1
,2
,12
]}

Gogola, Ewa ^{[5
]}

Bounova, Gergana ^{[6
,12
]}

Weeber, Fleur ^{[7
]}

Balgobind, Anjali Vanita ^{[3
]}

Wind, Karin ^{[1
,2
]}

Gracanin, Ana ^{[1
,2
]}

Begthel, Harry ^{[1
,2
]}

Korving, Jeroen ^{[1
,2
]}

van Boxtel, Ruben ^{[4
,12
]}

Duarte, Alexandra Alves ^{[5
]}

Lelieveld, Daphne ^{[8
]}

van Hoeck, Arne ^{[4
,12
]}

Ernst, Robert Frans ^{[4
,12
]}

Blokzijl, Francis ^{[4
,12
]}

Nijman, Isaac Johannes ^{[4
,12
]}

Hoogstraat, Marlous ^{[6
]}

van de Ven, Marieke ^{[9
]}

Egan, David Anthony ^{[8
]}

Zinzalla, Vittoria ^{[13
]}

Moll, Jurgen ^{[13
]}

Boj, Sylvia Fernandez ^{[3
,12
]}

Voest, Emile Eugene ^{[7
]}

Wessels, Lodewyk ^{[5
,12
,14
]}

van Diest, Paul Joannes ^{[10
]}

Rottenberg, Sven ^{[5
,11
]}

Vries, Robert Gerhardus Jacob ^{[3
,12
]}

Cuppen, Edwin ^{[4
,12
]}

Clevers, Hans ^{[1
,2
,12
]}

机构：

[1] Royal Netherlands Acad Arts & Sci, Hubrecht Inst, Uppsalalaan 8, NL-3584 CT Utrecht, Netherlands

[2] Univ Med Ctr Utrecht, Uppsalalaan 8, NL-3584 CT Utrecht, Netherlands

[3] Fdn Hubrecht Organoid Technol HUB, Yalelaan 62, NL-3584 CM Utrecht, Netherlands

[4] Univ Utrecht, Univ Med Ctr Utrecht, Ctr Mol Med, Dept Genet, Univ Weg 100, NL-3584 CG Utrecht, Netherlands

[5] Netherlands Canc Inst, Div Mol Pathol, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands

[6] Netherlands Canc Inst, Div Mol Carcinogenesis, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands

[7] Netherlands Canc Inst, Div Mol Oncol & Immunol, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands

[8] Univ Med Ctr, Cell Screening Core, Dept Cell Biol, Ctr Mol Med, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands

[9] Netherlands Canc Inst, MCCA, Preclin Intervent Unit, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands

[10] Univ Med Ctr Utrecht, Dept Pathol, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands

[11] Univ Bern, Inst Anim Pathol, Vetsuisse Fac, Langgassstr 122, CH-3012 Bern, Switzerland

[12] Canc Genom Netherlands, Oncode Inst, NL-3584 CG Utrecht, Netherlands

[13] Boehringer Ingelheim RCV GmbH & Co KG, Pharmacol & Translat Res, Dr Boehringer Gasse 5-11, A-1121 Vienna, Austria

[14] Delft Univ Technol, Fac EEMCS, Delft, Netherlands

[15] Vertex Pharmaceut Inc, San Diego, CA 92121 USA

来源：

CELL | 2018年 / 172卷 / 1-2期

关键词：

PATHOLOGICAL PROGNOSTIC-FACTORS; COPY NUMBER; R/BIOCONDUCTOR PACKAGE; MUTATIONAL PROCESSES; SOMATIC MUTATION; STEM-CELLS; IN-VITRO; EXPRESSION; GENOME; MODELS;

D O I：

10.1016/j.cell.2017.11.010

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Breast cancer (BC) comprises multiple distinct subtypes that differ genetically, pathologically, and clinically. Here, we describe a robust protocol for long-term culturing of human mammary epithelial organoids. Using this protocol, >100 primary and metastatic BC organoid lines were generated, broadly recapitulating the diversity of the disease. BC organoid morphologies typically matched the histopathology, hormone receptor status, and HER2 status of the original tumor. DNA copy number variations as well as sequence changes were consistent within tumor-organoid pairs and largely retained even after extended passaging. BC organoids furthermore populated all major gene-expression-based classification groups and allowed in vitro drug screens that were consistent with in vivo xeno-transplantations and patient response. This study describes a representative collection of well-characterized BC organoids available for cancer research and drug development, as well as a strategy to assess in vitro drug response in a personalized fashion.

引用

页码：373 / +

页数：24

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