An organoid biobank for childhood kidney cancers that captures disease and tissue heterogeneity
Calandrini, Camilla; Schutgens, Frans; Oka, Rurika; 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.; Rookmaaker, Maarten; Verhaar, Marianne; Tytgat, Godelieve A.M.; Kemmeren, Patrick; de Krijger, Ronald R.; Al-Saadi, Reem; Pritchard-Jones, Kathy; Kool, Marcel; Rios, Anne C.; van den Heuvel-Eibrink, Marry M.; Molenaar, Jan J.; van Boxtel, Ruben; Holstege, Frank C.P.; Clevers, Hans; Drost, Jarno
(2020) Nature Communications, volume 11, issue 1
(Article)
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
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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.
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Keywords: General Chemistry, General Biochemistry,Genetics and Molecular Biology, General Physics and Astronomy, Journal Article
ISSN: 2041-1723
Publisher: Nature Publishing Group
(Peer reviewed)