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

• Published in: Nature communications Vol. 11; no. 1; p. 1310
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 11.03.2020; Nature Publishing Group UK; Nature Portfolio
• Subjects: Adolescent; Biobanks; Biological Specimen Banks; Cancer; Carcinoma, Renal Cell - drug therapy; Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - pathology; Cell culture; Cell Culture Techniques - methods; Child; Child, Preschool; Children; DNA Methylation; Drug Screening Assays, Antitumor - methods; Female; Gene Expression Regulation, Neoplastic; Gene sequencing; Genetic Heterogeneity; Genetics; Genotyping Techniques; Heterogeneity; Humans; Image resolution; Infant; Kidney - pathology; Kidney cancer; Kidney Neoplasms - drug therapy; Kidney Neoplasms - genetics; Kidney Neoplasms - pathology; Kidneys; Male; Nephroma, Mesoblastic - drug therapy; Nephroma, Mesoblastic - genetics; Nephroma, Mesoblastic - pathology; Netherlands; Organoids; Organoids - pathology; Precision medicine; Precision Medicine - methods; Renal cell carcinoma; Rhabdoid Tumor - drug therapy; Rhabdoid Tumor - genetics; Rhabdoid Tumor - pathology; Ribonucleic acid; RNA; RNA-Seq; Single-Cell Analysis; Solid tumors; Transfection; Tumor Cells, Cultured; Tumors; Whole Genome Sequencing; Wilms Tumor - drug therapy; Wilms Tumor - genetics; Wilms Tumor - pathology; Young Adult; Netherlands
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-15155-6

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.