Improving the diagnosis of renal tumours of young people through integrated molecular analysis
Leiter, Sarah M Guobadia, Aisosa O Fleming, Ben Ajithkumar, Thankamma V Armitage, James N Burke, G A Amos Burns, Charlotte M Coleman, Nicholas Hatcher, Helen Horan, Gail
Leiter, Sarah M
Guobadia, Aisosa O
Fleming, Ben
Ajithkumar, Thankamma V
Armitage, James N
Burke, G A Amos
Burns, Charlotte M
Coleman, Nicholas
Hatcher, Helen
Horan, Gail
Abstract
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSION: 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.
MIDER Authors
Affiliations
Date
2026-04-03
Type
Article
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Citation
Leiter SM, Guobadia AO, Fleming B, Ajithkumar TV, Armitage JN, Burke GAA, Burns CM, Coleman N, Hatcher H, Horan G, Long AM, McDonald S, Mitchell TJ, Nicholson JC, Roberts T, Stewart GD, Tadross JA, Tarpey PS, Trayers C, Trotman J, Watkins JA, Warren AY, Vujanic GM, Armstrong R, Behjati S, Hook CE, Murray MJ. Improving the diagnosis of renal tumours of young people through integrated molecular analysis. J Cancer Res Clin Oncol. 2026 Apr 3;152(4):81. doi: 10.1007/s00432-026-06455-3