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

Published: 06/04/2020


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.

Full Access Link: Nature Communications