Renal tumours account for one in twenty paediatric cancers, with Wilms tumour (WT) the most common in young children and renal cell carcinoma (RCC) predominating in adolescents and young adults. Diagnostic work-up has traditionally focused on clinical features, radiology, and histology, with a limited role for molecular analysis. However, it is estimated that up to one-third of children with WT have underlying cancer predisposition, which could necessitate prolonged treatment and intensive follow-up.
Here we describe five children and young adults treated at a single regional centre in England who had paired tumour and germline whole genome sequencing (WGS) as part of their routine diagnostic work-up.
One child diagnosed radiologically with a WT underwent pre-operative chemotherapy with good clinical and imaging response. Histological examination of the resection raised concerns over RCC; however, WGS was able to confirm that this was a WT with pathognomonic somatic WT changes. A young adult with upfront nephrectomy had a difficult-to-classify tumour; WGS revealed a novel ERC1-CCNY fusion as a likely novel driver event. Two further children, who did not meet clinical criteria for cancer predisposition testing, had predisposition syndromes identified via agnostic WGS. Finally, a child with piebaldism had a WT-associated REST deletion identified early through critical clinical thinking and expedited microarray.
We highlight that molecular analysis, particularly agnostic WGS, has a key routine role in the care of children with renal tumours. It is likely that outcomes for these young people have been improved through more accurate diagnosis and early detection of cancer predisposition.
Journal of cancer research and clinical oncology. 2026 Apr 03*** epublish ***
Sarah M Leiter, Aisosa O Guobadia, Ben Fleming, Thankamma V Ajithkumar, James N Armitage, G A Amos Burke, Charlotte M Burns, Nicholas Coleman, Helen Hatcher, Gail Horan, Anna-May Long, Sarah McDonald, Thomas J Mitchell, James C Nicholson, Thomas Roberts, Grant D Stewart, John A Tadross, Patrick S Tarpey, Claire Trayers, Jamie Trotman, James A Watkins, Anne Y Warren, Gordan M Vujanic, Ruth Armstrong, Sam Behjati, C Elizabeth Hook, Matthew J Murray
Department of Paediatric Haematology and Oncology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK., Department of Radiology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK., Department of Clinical Oncology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK., Department of Urology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK., Cancer Research UK Clinical Trials Unit, School of Medical Sciences, University of Birmingham, Birmingham, B15 2TT, UK., Department of Histopathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK., Department of Oncology, Cambridge University Hospital NHS Trust, Cambridge, CB2 0QQ, UK., Department of Paediatric Surgery, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK., East Genomics Laboratory Hub (E-GLH) Genetics Laboratory, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK., Department of Pathology, Sidra Medicine, Doha, Qatar., Department of Clinical Genetics, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK., Department of Paediatric Haematology and Oncology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK. ., Department of Histopathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK. ., Department of Paediatric Haematology and Oncology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK. .