{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T16:14:53Z","timestamp":1787588093409,"version":"build-2736575974"},"reference-count":47,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,6,28]],"date-time":"2025-06-28T00:00:00Z","timestamp":1751068800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006244","name":"Stichting Kinderen Kankervrij","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006244","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p><jats:italic>SMARCA4<\/jats:italic> is a known susceptibility gene for malignant rhabdoid tumors (MRT) in children and small cell carcinoma of the ovary hypercalcemic type (SCCOHT) in young females and women. Recently, a novel association between germline <jats:italic>SMARCA4<\/jats:italic> variants and predisposition to neuroblastoma was proposed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We present a single\u2010center study summarizing the clinical and genetic data of pediatric and adolescent cancer patients with a germline <jats:italic>SMARCA4<\/jats:italic> variant diagnosed with and\/or treated for an MRT, SCCOHT, or neuroblastoma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified nine patients with germline <jats:italic>SMARCA4<\/jats:italic> variants, including one patient with an MRT, four patients with a SCCOHT, and four patients with a neuroblastoma. We observed two novel pathogenic <jats:italic>SMARCA4<\/jats:italic> variants that were initially missed using diagnostic testing: a low\u2010mosaic pathogenic <jats:italic>SMARCA4<\/jats:italic> variant in the patient with an MRT, and a germline <jats:italic>SMARCA4<\/jats:italic> partial gene deletion, encompassing the promoter region, in a patient with a SCCOHT. The patients with neuroblastoma in our cohort had a strikingly old age at diagnosis (range: 10\u201322\u00a0years old). In three of four patients with neuroblastoma, the germline <jats:italic>SMARCA4<\/jats:italic> variant was a variant of unknown significance (VUS). In two of their neuroblastomas, we observed loss of heterozygosity at the <jats:italic>SMARCA4<\/jats:italic> locus, and loss of BRG1 expression was found in one of these.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study highlights that awareness is needed for easy\u2010to\u2010miss germline variants in <jats:italic>SMARCA4<\/jats:italic> and that knowledge about variant types, cancer spectrum, and cancer penetrance in individuals with a germline <jats:italic>SMARCA4<\/jats:italic> variant is still evolving.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.31872","type":"journal-article","created":{"date-parts":[[2025,6,28]],"date-time":"2025-06-28T06:09:09Z","timestamp":1751090949000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Novel Findings in Pediatric and Adolescent Patients With Cancer and a Germline <i>SMARCA4<\/i> Variant"],"prefix":"10.1002","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2012-0611","authenticated-orcid":false,"given":"Nienke","family":"van Engelen","sequence":"first","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald. R.","family":"de Krijger","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology  Utrecht The Netherlands"},{"name":"Department of Pathology University Medical Center Utrecht  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle M.","family":"Kleisman","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lennart. A.","family":"Kester","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saskia M. J.","family":"Hopman","sequence":"additional","affiliation":[{"name":"Department of Genetics University Medical Center Utrecht Utrecht University  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariette E. G.","family":"Kranendonk","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marijn A.","family":"Vermeulen","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carli","family":"Tops","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8566-839X","authenticated-orcid":false,"given":"Seok\u2010Young","family":"Kim","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Clevers","sequence":"additional","affiliation":[{"name":"Hubrecht Institute Royal Netherlands Academy of Arts and Sciences and University Medical Center  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kornelia","family":"Neveling","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland. 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