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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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      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\n                      <jats:italic>ERC1-CCNY<\/jats:italic>\n                      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\n                      <jats:italic>REST<\/jats:italic>\n                      deletion identified early through critical clinical thinking and expedited microarray.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00432-026-06455-3","type":"journal-article","created":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T16:01:06Z","timestamp":1775232066000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Improving the diagnosis of renal tumours of young people through integrated molecular analysis"],"prefix":"10.1007","volume":"152","author":[{"given":"Sarah M.","family":"Leiter","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aisosa O.","family":"Guobadia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ben","family":"Fleming","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thankamma V.","family":"Ajithkumar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James N.","family":"Armitage","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G. 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N Engl J Med 373:2336\u20132346","journal-title":"N Engl J Med"}],"container-title":["Journal of Cancer Research and Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00432-026-06455-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00432-026-06455-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00432-026-06455-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T16:01:09Z","timestamp":1775232069000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00432-026-06455-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,3]]},"references-count":45,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["6455"],"URL":"https:\/\/doi.org\/10.1007\/s00432-026-06455-3","relation":{},"ISSN":["1432-1335"],"issn-type":[{"value":"1432-1335","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,3]]},"assertion":[{"value":"29 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 February 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 April 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"GDS has received educational grants from AstraZeneca; consultancy fees from Evinova; travel expenses from MSD; he is Clinical lead (urology) National Kidney Cancer Audit and Topic Advisor for the NICE kidney cancer guideline.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Our study protocol entitled \u2018Assessing the Clinical Benefits of Whole Genome Sequencing for Children with Neoplasms\u2019 was approved by an NHS Research Ethics Committee (reference 22\/WA\/0281) and, in accordance, we declare that the research was performed following the guidelines of this ethics committee.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}],"article-number":"81"}}