{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T15:36:06Z","timestamp":1778600166322,"version":"3.51.4"},"reference-count":12,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,6,22]],"date-time":"2023-06-22T00:00:00Z","timestamp":1687392000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Nephroblastoma (Wilms tumor (WT)) is an embryonal tumor accounting for &amp;gt;90% of pediatric renal cancers. About 10% of WTs harbor pathogenic germline mutations. The <jats:italic>REST<\/jats:italic> gene, classified as a putative tumor suppressor, is affected in 2% of WTs. High-throughput molecular methods facilitate advanced diagnostics of cancer. In addition to this, germline mutations in <jats:italic>REST<\/jats:italic> are also associated with familial gingival fibromatosis (GFM). Reciprocally, none of the articles on <jats:italic>REST<\/jats:italic>mut WT mentions GFM as a comorbid condition. This report provides unique evidence on the WT-GFM comorbidity in <jats:italic>REST<\/jats:italic>mut carriers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Case presentation<\/jats:title><jats:p>Patient 1 (a 5-year-old boy with unilateral WT) is a proband, who has two healthy siblings. Patient 2 (a 4-year-old girl with bilateral WT) is a proband from <jats:italic>in vitro<\/jats:italic> fertilization (IVF) triplets, with a sister and brother without WT. We analyzed probands\u2019 DNA extracted from peripheral blood leucocytes with a custom-targeted next-generation sequencing (NGS)-198 gene panel. The detected variants were checked in family members by Sanger sequencing. Patient 1 had a pathogenic germline mutation in <jats:italic>REST:<\/jats:italic> c.1035_1036insTA, p.(E346*), as did his mother and both brothers. There were two other WT cases in this family (proband\u2019s maternal uncles). Patient 2 had a pathogenic germline variant in <jats:italic>REST<\/jats:italic>: c.2668_2671del, p.(E891Pfs*6), as well as her sister. The mutation was probably inherited from their deceased father, as he had gingival fibromatosis. Family members with <jats:italic>REST<\/jats:italic> mutations from both families had gingival fibromatosis. A somatic <jats:italic>REST<\/jats:italic> c.663C&amp;gt;A p.C221* mutation was identified in one patient with WT. At the moment both patients with WT are under dynamic observation without signs of the disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Here, we describe two clinical cases of WT in nonrelated young children with germline-inactivating <jats:italic>REST<\/jats:italic> variants identified by next-generation sequencing. Both patients present with familial gingival fibromatosis, regarded as clinically useful comorbidity indicative of the tumor predisposition syndrome. The two cases illustrate Wilms tumor-gingival fibromatosis comorbidity in carriers of germline-inactivated <jats:italic>REST<\/jats:italic> alleles previously identified as a predisposition factor for both conditions.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2023.1192489","type":"journal-article","created":{"date-parts":[[2023,6,24]],"date-time":"2023-06-24T03:12:09Z","timestamp":1687576329000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Case Report: Two clinical cases of Wilms tumor comorbid to gingival fibromatosis in young children with constitutionally mutated REST"],"prefix":"10.3389","volume":"13","author":[{"given":"Anastasiya S.","family":"Salomatina","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liudmila A.","family":"Yasko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria A.","family":"Kurnikova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yulia M.","family":"Mareeva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruslan K.","family":"Abasov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nina V.","family":"Gegeliya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna M.","family":"Mitrofanova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalia Y.","family":"Usman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Galina A.","family":"Novichkova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander E.","family":"Druy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,6,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"409","DOI":"10.3109\/08880018.2014.930767","article-title":"Wilms\u2019 tumor: a 24-year retrospective study from a single center","volume":"31","author":"Erginel","year":"2014","journal-title":"Pediatr Hematol Oncol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1097\/mop.0000000000000988","article-title":"New approaches to risk stratification for wilms tumor","volume":"33","author":"Nelson","year":"2021","journal-title":"Curr Opin Pediatr"},{"key":"B3","volume-title":"Wilms\u2019 tumour: a systematic review of risk factors and meta-analysis","author":"Chu","year":"2010"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.21037\/tau.2020.03.27","article-title":"Syndromic wilms tumor: a review of predisposing conditions, surveillance 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