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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

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
Authors: Lauren McAuley; Orla Fitzpatrick; Nicola Cosgrove; Jad Yacoub; Liam Grogan; Bryan T. Hennessy; Simon J. Furney; Sinead Toomey
Source: Frontiers in Oncology, Vol 16 (2026)
Publisher Information: Frontiers Media S.A.
Publication Year: 2026
Collection: Directory of Open Access Journals: DOAJ Articles
Subject Terms: cancer; case report; CLOVES syndrome; PIK3CA; PIK3CA-related overgrowth spectrum; urothelial carcinoma; Neoplasms. Tumors. Oncology. Including cancer and carcinogens; RC254-282
Description: Congenital lipomatous overgrowth, vascular epidermal nevi, and skeletal abnormalities (CLOVES) syndrome is a rare genetic disorder caused by somatic activating mutations in the PIK3CA gene that arise during embryonic development. Mutations in the PI3K–AKT–mTOR pathway have been linked to various benign overgrowth disorders, including syndromes within the PIK3CA-related overgrowth spectrum. Somatic PIK3CA 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 CDKN2A and CDKN2B. In this case, we could not detect somatic PIK3CA alterations in this patient’s urothelial carcinoma and suggest that it is unrelated to CLOVES syndrome.
Document Type: article in journal/newspaper
Language: English
Relation: https://www.frontiersin.org/articles/10.3389/fonc.2026.1704090/full; https://doaj.org/toc/2234-943X; https://doaj.org/article/9a7e150aadc04b35aa5f41ca2affe56e
DOI: 10.3389/fonc.2026.1704090
Availability: https://doi.org/10.3389/fonc.2026.1704090; https://doaj.org/article/9a7e150aadc04b35aa5f41ca2affe56e
Accession Number: edsbas.8A54A8A8
Database: BASE