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

Congenital lipomatous overgrowth, vascular epidermal nevi, and skeletal abnormalities (CLOVES) syndrome is a rare genetic disorder caused by somatic activating mutations in the <i>PIK3CA</i> 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 <i>PIK3CA</i>-related overgrowth spectrum. Somatic <i>PIK3CA</i> 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 <i>CDKN2A</i> and <i>CDKN2B</i>. In this case, we could not detect somatic <i>PIK3CA</i> alterations in this patient's urothelial carcinoma and suggest that it is unrelated to CLOVES syndrome.