{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T06:04:20Z","timestamp":1771567460909,"version":"3.50.1"},"reference-count":17,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T00:00:00Z","timestamp":1771545600000},"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:p>\n                    Congenital lipomatous overgrowth, vascular epidermal nevi, and skeletal abnormalities (CLOVES) syndrome is a rare genetic disorder caused by somatic activating mutations in the\n                    <jats:italic>PIK3CA<\/jats:italic>\n                    gene that arise during embryonic development. Mutations in the PI3K\u2013AKT\u2013mTOR pathway have been linked to various benign overgrowth disorders, including syndromes within the\n                    <jats:italic>PIK3CA<\/jats:italic>\n                    -related overgrowth spectrum. Somatic\n                    <jats:italic>PIK3CA<\/jats:italic>\n                    mutations also occur frequently across many cancer types; however, evidence linking CLOVES syndrome to increased cancer risk is not conclusive. Here, we describe a whole-genome sequencing (WGS) study of a primary pT3 high-grade urothelial carcinoma in a 62-year-old male patient diagnosed with CLOVES syndrome. A left laparoscopic nephroureterectomy was completed. Tumour tissue and a matched blood sample were collected for whole-genome sequencing, and somatic variant detection was performed. The somatic alterations were consistent with previous reports of urothelial carcinoma, including homozygous deletions of\n                    <jats:italic>CDKN2A<\/jats:italic>\n                    and\n                    <jats:italic>CDKN2B<\/jats:italic>\n                    . In this case, we could not detect somatic\n                    <jats:italic>PIK3CA<\/jats:italic>\n                    alterations in this patient\u2019s urothelial carcinoma and suggest that it is unrelated to CLOVES syndrome.\n                  <\/jats:p>","DOI":"10.3389\/fonc.2026.1704090","type":"journal-article","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T05:21:16Z","timestamp":1771564876000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Whole-genome sequencing of urothelial carcinoma in an adult patient with CLOVES syndrome reveals a lack of PIK3CA mutation and a genomic landscape consistent with urothelial carcinoma"],"prefix":"10.3389","volume":"16","author":[{"given":"Lauren","family":"McAuley","sequence":"first","affiliation":[{"name":"Genomic Oncology Research Group, Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland","place":["Dublin, Ireland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Orla","family":"Fitzpatrick","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Beaumont Hospital","place":["Dublin, Ireland"]},{"name":"Cancer Clinical Trials and Research Unit, Beaumont Hospital","place":["Dublin, Ireland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola","family":"Cosgrove","sequence":"additional","affiliation":[{"name":"Genomic Oncology Research Group, Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland","place":["Dublin, Ireland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jad","family":"Yacoub","sequence":"additional","affiliation":[{"name":"Genomic Oncology Research Group, Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland","place":["Dublin, Ireland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liam","family":"Grogan","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Beaumont Hospital","place":["Dublin, Ireland"]},{"name":"Cancer Clinical Trials and Research Unit, Beaumont Hospital","place":["Dublin, Ireland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bryan T.","family":"Hennessy","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Beaumont Hospital","place":["Dublin, Ireland"]},{"name":"Medical Oncology Group, Department of Molecular Medicine, Royal College of Surgeons in Ireland","place":["Dublin, Ireland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon J.","family":"Furney","sequence":"additional","affiliation":[{"name":"Genomic Oncology Research Group, Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland","place":["Dublin, Ireland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sinead","family":"Toomey","sequence":"additional","affiliation":[{"name":"Medical Oncology Group, Department of Molecular Medicine, Royal College of Surgeons in Ireland","place":["Dublin, Ireland"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-023-31593-w","article-title":"PIK3CA and PIK3R1 tumor mutational landscape in a pan-cancer patient cohort and its association with pathway activation and treatment efficacy","volume":"13","author":"Tharin","year":"2023","journal-title":"Sci Rep"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e63466","DOI":"10.1002\/ajmg.a.63466","article-title":"Molecular characterization of 13 patients with PIK3CA-related overgrowth spectrum using a targeted deep sequencing approach","volume":"194","author":"de Kock","year":"2024","journal-title":"Am J Med Genet A"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2018.08.003","article-title":"Cancer-associated PIK3CA mutations in overgrowth disorders","volume":"24","author":"Madsen","year":"2018","journal-title":"Trends Mol Med"},{"key":"B4","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1002\/AJMG.A.36836","article-title":"PIK3CA-related overgrowth spectrum (PROS): diagnostic and testing eligibility criteria, differential diagnosis, and evaluation","author":"Keppler-Noreuil","year":"2014","journal-title":"Am J Med Genet A"},{"key":"B5","doi-asserted-by":"publisher","first-page":"e30393","DOI":"10.1002\/pbc.30393","article-title":"A case of high-risk neuroblastoma in a child with CLOVES syndrome","volume":"70","author":"Girgis","year":"2023","journal-title":"Pediatr Blood Cancer"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2020.153285","article-title":"Molecular analysis of a uterine broad ligament leiomyoma in a patient with CLOVES syndrome","volume":"216","author":"Karpathiou","year":"2020","journal-title":"Pathol Res Pract"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1111\/cge.14410","article-title":"Low risk of embryonic and other cancers in PIK3CA-related overgrowth spectrum: Impact on screening recommendations","volume":"104","author":"Faivre","year":"2023","journal-title":"Clin Genet"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-019-0720-x","article-title":"Prevalence of pathogenic germline cancer risk variants in high-risk urothelial carcinoma","volume":"22","author":"Nassar","year":"2020","journal-title":"Genetics in Medicine"},{"key":"B9","doi-asserted-by":"publisher","first-page":"4586","DOI":"10.1158\/1078-0432.CCR-23-1283","article-title":"Clinical and genomic landscape of FGFR3-altered urothelial carcinoma and treatment outcomes with erdafitinib: a real-world experience","volume":"29","author":"Guercio","year":"2023","journal-title":"Clin Cancer Res"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2013.135","article-title":"Advanced urothelial carcinoma: next-generation sequencing reveals diverse genomic alterations and targets of therapy","volume":"27","author":"Ross","year":"2013","journal-title":"Mod Pathol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"4104","DOI":"10.1128\/MCB.00289-08","article-title":"The TSC1-TSC2 complex is required for proper activation of mTOR complex 2","volume":"28","author":"Huang","year":"2008","journal-title":"Mol Cell Biol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-021-01765-x","article-title":"PRDM4 inhibits cell proliferation and tumorigenesis by inactivating the PI3K\/AKT signaling pathway through targeting of PTEN in cervical carcinoma","volume":"40","author":"Yang","year":"2021","journal-title":"Oncogene"},{"key":"B13","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1038\/NG.2329","article-title":"De novo somatic mutations in components of the PI3K-AKT3-mTOR pathway cause hemimegalencephaly","volume":"44","author":"Lee","year":"2012","journal-title":"Nat Genet"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1048","DOI":"10.1016\/J.JPEDS.2014.12.069","article-title":"Lymphatic and other vascular malformative\/overgrowth disorders are caused by somatic mutations in PIK3CA","volume":"166","author":"Luks","year":"2015","journal-title":"J Pediatr"},{"key":"B15","doi-asserted-by":"publisher","first-page":"e26684","DOI":"10.1002\/PBC.26684","article-title":"Sonographic screening for Wilms tumor in children with CLOVES syndrome","volume":"64","author":"Peterman","year":"2017","journal-title":"Pediatr Blood Cancer"},{"key":"B16","doi-asserted-by":"publisher","first-page":"e1252","DOI":"10.1002\/CTM2.1252","article-title":"Tumour purity as an underlying key factor in tumour mutation detection in colorectal cancer","volume":"13","author":"Yu","year":"2023","journal-title":"Clin Transl Med"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2023.07.001","article-title":"Urothelium-specific expression of mutationally activated Pik3ca initiates early lesions of non-invasive bladder cancer","volume":"193","author":"Shuman","year":"2023","journal-title":"The American Journal of Pathology"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1704090\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T05:21:17Z","timestamp":1771564877000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1704090\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,20]]},"references-count":17,"alternative-id":["10.3389\/fonc.2026.1704090"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2026.1704090","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,20]]},"article-number":"1704090"}}