Molecular characterisation of oncogenic urothelial mosaic mutations in patients with extensive keratinocytic epidermal naevi
| Autor: | Inmaculada Hernández-Muñoz, Evelyn Andrades, Laura Camacho, Ramon M. Pujol, Alejandra Gadea, Miriam García-Calvente, Conchi Fernandez-Rodríguez, Asunción Vicente, Beatriz Bellosillo, Agustín Toll |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
Keratinocytes Male 0301 basic medicine Skin Neoplasms Carcinogenesis Biology medicine.disease_cause Malignant transformation Proto-Oncogene Proteins p21(ras) Young Adult 03 medical and health sciences 0302 clinical medicine Genetics medicine Humans In patient HRAS Receptor Fibroblast Growth Factor Type 2 Urothelium Nevus Gene Genetics (clinical) Mutation Middle Aged Highly sensitive 030104 developmental biology 030220 oncology & carcinogenesis Cancer research Female Screening measures |
| Zdroj: | Journal of Medical Genetics. 57:601-604 |
| ISSN: | 1468-6244 0022-2593 |
| DOI: | 10.1136/jmedgenet-2019-106296 |
| Popis: | Background: Keratinocytic epidermal naevi (KENs) are congenital benign skin mosaic lesions that share common mutations with some subsets of urothelial carcinomas. Moreover, several patients with extensive KEN who also developed urothelial carcinomas at young ages have been reported. Thus, patients with extensive KEN may harbour mosaic urothelial oncogenic mutations that would favour the early development of urothelial carcinomas. Methods: We selected five patients with extensive KEN involving the lower part of the back and performed a molecular characterisation of urothelial and cutaneous samples using a next-generation sequencing (NGS) custom panel targeting candidate oncogenic genes. Results: Mosaic pathogenic mutations were detected in KEN in all patients. In four out of five patients, mosaic pathogenic mutations in FGFR2 or HRAS were also detected in samples from the urothelial tract. Moreover, we report a patient who developed urothelial carcinomas at age 29 and harboured an HRAS G12S mutation both in skin and urothelial tumour samples. Conclusions: We conclude that patients with extensive KEN involving the lower part of the back frequently harbour oncogenic mutations in the urothelium that may induce the development of carcinomas. NGS panels can be considered as highly sensitive tools to identify this subgroup of patients, which might permit adoption of screening measures to detect malignant transformation at early stages. |
| Databáze: | OpenAIRE |
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