Case Report: Whole genome sequencing of urothelial carcinoma in an adult patient with CLOVES syndrome reveals lack of PIK3CA mutation and genomic landscape consistent with urothelial carcinoma

Lauren McAuley¹Orla Fitzpatrick^2,3Nicola Cosgrove¹Jad Yacoub¹Liam Grogan^2,3Bryan T Hennessy^2,4Simon J Furney^1*Sinead Toomey^4*

• ¹Genomic Oncology Research Group, Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland
• ²Department of Medical Oncology, Beaumont Hospital, Dublin, Ireland
• ³Cancer Clinical Trials and Research Unit, Beaumont Hospital, Dublin, Ireland
• ⁴Medical Oncology Group, Department of Molecular Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland

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 other PIK3CA-related overgrowth syndromes. 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 and matched blood were collected for whole genome sequencing and somatic variant detection was performed. 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.