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

TLDR

Kidney tumours are among the most common solid tumours in children, with distinct subtypes differing in cell‑of‑origin, genetics, and pathology, yet pre‑clinical cell models that capture this heterogeneity are lacking. Here, we describe the first paediatric cancer organoid biobank. The biobank comprises tumour and matched normal kidney organoids from over 50 children across diverse kidney cancer subtypes, such as Wilms tumours, malignant rhabdoid tumours, renal cell carcinomas, and congenital mesoblastic nephromas. Paediatric kidney tumour organoids preserve key tumour properties, reveal patient‑specific drug sensitivities, and, as shown by single‑cell RNA‑seq and 3D imaging, contain multiple cell types; thus the biobank captures tumour heterogeneity and provides well‑characterised models for basic research, drug screening, and personalised medicine.

Abstract

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.