Improving the diagnosis of renal tumours of young people through integrated molecular analysis

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.

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Journal
Journal of Cancer Research and Clinical Oncology
Published
2026-04-03
DOI
https://doi.org/10.1007/s00432-026-06455-3
Primary Topic
Renal and related cancers
Type
article
Field-Weighted Citation Impact
0.00

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article

Improving the diagnosis of renal tumours of young people through integrated molecular analysis

Thankamma Ajithkumar, Gail Horan, Ben J. Fleming, Claire Trayers et al.
Journal of Cancer Research and Clinical Oncology
Renal and related cancers
article

Improving the diagnosis of renal tumours of young people through integrated molecular analysis

Thankamma Ajithkumar, Gail Horan, Ben J. Fleming, Claire Trayers, Patrick S. Tarpey, Anne Y. Warren, Nicholas Coleman, James C. Nicholson, Sarah M. Leiter, Matthew J. Murray, Anna‐May Long, James Watkins, Jamie Trotman, John A. Tadross, Thomas J. Mitchell, Helen Hatcher, James N. Armitage, C. Elizabeth Hook, Ruth Armstrong, Gordan M. Vujanic, Aisosa O. Guobadia, Sam Behjati, Charlotte M. Burns, G. A. Amos Burke, Grant D. Stewart, Thomas Roberts, Sarah McDonald
article en

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.

Journal of Cancer Research and Clinical OncologyVol. 152(4)
University of Cambridge (GB), Cambridge University Hospitals NHS Foundation Trust (GB), Wellcome Sanger Institute (GB), Cambridge School (PT), Wellcome/MRC Institute of Metabolic Science (GB), Cancer Research UK Clinical Trials Unit (GB), Weill Cornell Medical College in Qatar (QA), Birmingham Women’s and Children’s NHS Foundation Trust (GB), Wellcome Trust (GB), Medical Research Council (GB)
Wellcome Trust, Children's Cancer and Leukaemia Group, Mark Foundation For Cancer Research, Cancer Research UK, National Institute for Health and Care Research, University of Cambridge, NIHR Cambridge Biomedical Research Centre, Cancer Research UK Cambridge Institute, University of Cambridge
Openalex Percentile: Top 31%
Renal and related cancers
DOIOpen Access PDFOpenAlex
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