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

Author:

Calandrini Camilla,Schutgens Frans,Oka RurikaORCID,Margaritis Thanasis,Candelli Tito,Mathijsen Luka,Ammerlaan Carola,van Ineveld Ravian L.,Derakhshan Sepide,de Haan Sanne,Dolman Emmy,Lijnzaad Philip,Custers Lars,Begthel Harry,Kerstens Hindrik H. D.,Visser Lindy L.ORCID,Rookmaaker Maarten,Verhaar MarianneORCID,Tytgat Godelieve A. M.,Kemmeren PatrickORCID,de Krijger Ronald R.,Al-Saadi ReemORCID,Pritchard-Jones KathyORCID,Kool Marcel,Rios Anne C.,van den Heuvel-Eibrink Marry M.,Molenaar Jan J.,van Boxtel RubenORCID,Holstege Frank C. P.ORCID,Clevers HansORCID,Drost Jarno

Abstract

AbstractKidney 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.

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry

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