An organoid biobank for childhood kidney cancers that captures disease and tissue heterogeneity

Camilla Calandrini; Frans Schutgens; Rurika Oka; Thanasis Margaritis; Tito Candelli; Luka Mathijsen; Carola Ammerlaan; Ravian L van Ineveld; Sepide Derakhshan; Sanne de Haan; Emmy Dolman; Philip Lijnzaad; Lars Custers; Harry Begthel; Hindrik H D Kerstens; Lindy L Visser; Maarten Rookmaaker; Marianne Verhaar; Godelieve A M Tytgat; Patrick Kemmeren; Ronald R de Krijger; Reem Al-Saadi; Kathy Pritchard-Jones; Marcel Kool; Anne C Rios; Marry M van den Heuvel-Eibrink; Jan J Molenaar; Ruben van Boxtel; Frank C P Holstege; Hans Clevers; Jarno Drost

doi:10.1038/s41467-020-15155-6

An organoid biobank for childhood kidney cancers that captures disease and tissue heterogeneity

Camilla Calandrini, Frans Schutgens, Rurika Oka, Thanasis Margaritis, Tito Candelli, Luka Mathijsen, Carola Ammerlaan, Ravian L van Ineveld, Sepide Derakhshan, Sanne de Haan, Emmy Dolman, Philip Lijnzaad, Lars Custers, Harry Begthel, Hindrik H D Kerstens, Lindy L Visser, Maarten Rookmaaker, Marianne Verhaar, Godelieve A M Tytgat, Patrick KemmerenRonald R de Krijger, Reem Al-Saadi, Kathy Pritchard-Jones, Marcel Kool, Anne C Rios, Marry M van den Heuvel-Eibrink, Jan J Molenaar, Ruben van Boxtel, Frank C P Holstege, Hans Clevers, Jarno Drost

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

Abstract

Kidney tumours are among the most common solid tumours in children, comprising distinct subtypes differing in many aspects, including cell-of-origin, genetics, and pathology. Pre-clinical cell models capturing the disease heterogeneity are currently lacking. Here, we describe the first paediatric cancer organoid biobank. It contains tumour and matching normal kidney organoids from over 50 children with different subtypes of kidney cancer, including Wilms tumours, malignant rhabdoid tumours, renal cell carcinomas, and congenital mesoblastic nephromas. Paediatric kidney tumour organoids retain key properties of native tumours, useful for revealing patient-specific drug sensitivities. Using single cell RNA-sequencing and high resolution 3D imaging, we further demonstrate that organoid cultures derived from Wilms tumours consist of multiple different cell types, including epithelial, stromal and blastemal-like cells. Our organoid biobank captures the heterogeneity of paediatric kidney tumours, providing a representative collection of well-characterised models for basic cancer research, drug-screening and personalised medicine.

Original language	English
Article number	1310
Number of pages	14
Journal	Nature Communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-15155-6
Publication status	Published - 11 Mar 2020

Keywords

Adolescent
Biological Specimen Banks
Carcinoma, Renal Cell/drug therapy
Cell Culture Techniques/methods
Child
Child, Preschool
DNA Methylation
Drug Screening Assays, Antitumor/methods
Female
Gene Expression Regulation, Neoplastic
Genetic Heterogeneity
Genotyping Techniques
Humans
Infant
Kidney/pathology
Kidney Neoplasms/drug therapy
Male
Nephroma, Mesoblastic/drug therapy
Netherlands
Organoids/pathology
Precision Medicine/methods
RNA-Seq
Rhabdoid Tumor/drug therapy
Single-Cell Analysis
Transfection
Tumor Cells, Cultured
Whole Genome Sequencing
Wilms Tumor/drug therapy
Young Adult

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Calandrini, C., Schutgens, F., Oka, R., Margaritis, T., Candelli, T., Mathijsen, L., Ammerlaan, C., van Ineveld, R. L., Derakhshan, S., de Haan, S., Dolman, E., Lijnzaad, P., Custers, L., Begthel, H., Kerstens, H. H. D., Visser, L. L., Rookmaaker, M., Verhaar, M., Tytgat, G. A. M., ... Drost, J. (2020). An organoid biobank for childhood kidney cancers that captures disease and tissue heterogeneity. Nature Communications, 11(1), Article 1310. https://doi.org/10.1038/s41467-020-15155-6

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title = "An organoid biobank for childhood kidney cancers that captures disease and tissue heterogeneity",

abstract = "Kidney tumours are among the most common solid tumours in children, comprising distinct subtypes differing in many aspects, including cell-of-origin, genetics, and pathology. Pre-clinical cell models capturing the disease heterogeneity are currently lacking. Here, we describe the first paediatric cancer organoid biobank. It contains tumour and matching normal kidney organoids from over 50 children with different subtypes of kidney cancer, including Wilms tumours, malignant rhabdoid tumours, renal cell carcinomas, and congenital mesoblastic nephromas. Paediatric kidney tumour organoids retain key properties of native tumours, useful for revealing patient-specific drug sensitivities. Using single cell RNA-sequencing and high resolution 3D imaging, we further demonstrate that organoid cultures derived from Wilms tumours consist of multiple different cell types, including epithelial, stromal and blastemal-like cells. Our organoid biobank captures the heterogeneity of paediatric kidney tumours, providing a representative collection of well-characterised models for basic cancer research, drug-screening and personalised medicine.",

keywords = "Adolescent, Biological Specimen Banks, Carcinoma, Renal Cell/drug therapy, Cell Culture Techniques/methods, Child, Child, Preschool, DNA Methylation, Drug Screening Assays, Antitumor/methods, Female, Gene Expression Regulation, Neoplastic, Genetic Heterogeneity, Genotyping Techniques, Humans, Infant, Kidney/pathology, Kidney Neoplasms/drug therapy, Male, Nephroma, Mesoblastic/drug therapy, Netherlands, Organoids/pathology, Precision Medicine/methods, RNA-Seq, Rhabdoid Tumor/drug therapy, Single-Cell Analysis, Transfection, Tumor Cells, Cultured, Whole Genome Sequencing, Wilms Tumor/drug therapy, Young Adult",

author = "Camilla Calandrini and Frans Schutgens and Rurika Oka and Thanasis Margaritis and Tito Candelli and Luka Mathijsen and Carola Ammerlaan and {van Ineveld}, {Ravian L} and Sepide Derakhshan and {de Haan}, Sanne and Emmy Dolman and Philip Lijnzaad and Lars Custers and Harry Begthel and Kerstens, {Hindrik H D} and Visser, {Lindy L} and Maarten Rookmaaker and Marianne Verhaar and Tytgat, {Godelieve A M} and Patrick Kemmeren and {de Krijger}, {Ronald R} and Reem Al-Saadi and Kathy Pritchard-Jones and Marcel Kool and Rios, {Anne C} and {van den Heuvel-Eibrink}, {Marry M} and Molenaar, {Jan J} and {van Boxtel}, Ruben and Holstege, {Frank C P} and Hans Clevers and Jarno Drost",

year = "2020",

month = mar,

day = "11",

doi = "10.1038/s41467-020-15155-6",

language = "English",

volume = "11",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

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Calandrini, C, Schutgens, F, Oka, R, Margaritis, T, Candelli, T, Mathijsen, L, Ammerlaan, C, van Ineveld, RL, Derakhshan, S, de Haan, S, Dolman, E, Lijnzaad, P, Custers, L, Begthel, H, Kerstens, HHD, Visser, LL, Rookmaaker, M, Verhaar, M, Tytgat, GAM, Kemmeren, P, de Krijger, RR, Al-Saadi, R, Pritchard-Jones, K, Kool, M, Rios, AC, van den Heuvel-Eibrink, MM, Molenaar, JJ, van Boxtel, R, Holstege, FCP, Clevers, H & Drost, J 2020, 'An organoid biobank for childhood kidney cancers that captures disease and tissue heterogeneity', Nature Communications, vol. 11, no. 1, 1310. https://doi.org/10.1038/s41467-020-15155-6

TY - JOUR

T1 - An organoid biobank for childhood kidney cancers that captures disease and tissue heterogeneity

AU - Calandrini, Camilla

AU - Schutgens, Frans

AU - Oka, Rurika

AU - Margaritis, Thanasis

AU - Candelli, Tito

AU - Mathijsen, Luka

AU - Ammerlaan, Carola

AU - van Ineveld, Ravian L

AU - Derakhshan, Sepide

AU - de Haan, Sanne

AU - Dolman, Emmy

AU - Lijnzaad, Philip

AU - Custers, Lars

AU - Begthel, Harry

AU - Kerstens, Hindrik H D

AU - Visser, Lindy L

AU - Rookmaaker, Maarten

AU - Verhaar, Marianne

AU - Tytgat, Godelieve A M

AU - Kemmeren, Patrick

AU - de Krijger, Ronald R

AU - Al-Saadi, Reem

AU - Pritchard-Jones, Kathy

AU - Kool, Marcel

AU - Rios, Anne C

AU - van den Heuvel-Eibrink, Marry M

AU - Molenaar, Jan J

AU - van Boxtel, Ruben

AU - Holstege, Frank C P

AU - Clevers, Hans

AU - Drost, Jarno

PY - 2020/3/11

Y1 - 2020/3/11

N2 - Kidney tumours are among the most common solid tumours in children, comprising distinct subtypes differing in many aspects, including cell-of-origin, genetics, and pathology. Pre-clinical cell models capturing the disease heterogeneity are currently lacking. Here, we describe the first paediatric cancer organoid biobank. It contains tumour and matching normal kidney organoids from over 50 children with different subtypes of kidney cancer, including Wilms tumours, malignant rhabdoid tumours, renal cell carcinomas, and congenital mesoblastic nephromas. Paediatric kidney tumour organoids retain key properties of native tumours, useful for revealing patient-specific drug sensitivities. Using single cell RNA-sequencing and high resolution 3D imaging, we further demonstrate that organoid cultures derived from Wilms tumours consist of multiple different cell types, including epithelial, stromal and blastemal-like cells. Our organoid biobank captures the heterogeneity of paediatric kidney tumours, providing a representative collection of well-characterised models for basic cancer research, drug-screening and personalised medicine.

AB - Kidney tumours are among the most common solid tumours in children, comprising distinct subtypes differing in many aspects, including cell-of-origin, genetics, and pathology. Pre-clinical cell models capturing the disease heterogeneity are currently lacking. Here, we describe the first paediatric cancer organoid biobank. It contains tumour and matching normal kidney organoids from over 50 children with different subtypes of kidney cancer, including Wilms tumours, malignant rhabdoid tumours, renal cell carcinomas, and congenital mesoblastic nephromas. Paediatric kidney tumour organoids retain key properties of native tumours, useful for revealing patient-specific drug sensitivities. Using single cell RNA-sequencing and high resolution 3D imaging, we further demonstrate that organoid cultures derived from Wilms tumours consist of multiple different cell types, including epithelial, stromal and blastemal-like cells. Our organoid biobank captures the heterogeneity of paediatric kidney tumours, providing a representative collection of well-characterised models for basic cancer research, drug-screening and personalised medicine.

KW - Adolescent

KW - Biological Specimen Banks

KW - Carcinoma, Renal Cell/drug therapy

KW - Cell Culture Techniques/methods

KW - Child

KW - Child, Preschool

KW - DNA Methylation

KW - Drug Screening Assays, Antitumor/methods

KW - Female

KW - Gene Expression Regulation, Neoplastic

KW - Genetic Heterogeneity

KW - Genotyping Techniques

KW - Humans

KW - Infant

KW - Kidney/pathology

KW - Kidney Neoplasms/drug therapy

KW - Male

KW - Nephroma, Mesoblastic/drug therapy

KW - Netherlands

KW - Organoids/pathology

KW - Precision Medicine/methods

KW - RNA-Seq

KW - Rhabdoid Tumor/drug therapy

KW - Single-Cell Analysis

KW - Transfection

KW - Tumor Cells, Cultured

KW - Whole Genome Sequencing

KW - Wilms Tumor/drug therapy

KW - Young Adult

U2 - 10.1038/s41467-020-15155-6

DO - 10.1038/s41467-020-15155-6

M3 - Article

C2 - 32161258

SN - 2041-1723

VL - 11

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 1310

ER -

An organoid biobank for childhood kidney cancers that captures disease and tissue heterogeneity

Abstract

Keywords

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