Overview

• Researchers applied nanorate sequencing and whole-genome analysis of single-cell organoids to Wilms tumor samples from infants, uncovering 72 to 111 additional mutations per cell and millions per tumor overall.
• The unexpectedly high mutational burden challenges the view that childhood cancers are genetically simple and suggests these tumors could respond to immunotherapies used in adult oncology.
• Tumor evolution mapping identified a spontaneous FOXR2 gene mutation arising during fetal kidney development that defines a rare congenital Wilms tumor subtype.
• The FOXR2 mutation’s distinctive histology and genetic profile offer a biomarker for tailored diagnostics and the development of individualized treatment regimens.
• With roughly 85 UK children diagnosed with Wilms tumor each year, the findings underscore an urgent need for new therapeutic strategies informed by detailed genomic insights.