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Molecular characterisation of oncogenic urothelial mosaic mutations in patients with extensive keratinocytic epidermal naevi
  1. Alejandra Gadea1,
  2. Inmaculada Hernández-Muñoz1,
  3. Asunción Vicente2,
  4. Evelyn Andrades1,
  5. Miriam García-Calvente3,
  6. Laura Camacho4,
  7. Conchi Fernandez-Rodríguez5,
  8. Beatriz Bellosillo4,6,
  9. Ramon Pujol1,7,
  10. Agustín Toll8
  1. 1 Group of Inflammatory and Neoplastic Dermatological Diseases, IMIM, Barcelona, Catalunya, Spain
  2. 2 Dermatology, Sant Joan de Deu Hospital, Barcelona, Catalunya, Spain
  3. 3 Department of Medicine, University of Barcelona, Barcelona, Catalunya, Spain
  4. 4 Department of Pathology, Hospital del Mar, Barcelona, Catalunya, Spain
  5. 5 Department of Pathology, Consorci Parc de Salut MAR de Barcelona, Barcelona, Catalunya, Spain
  6. 6 Cancer Research Program, IMIM (Hospital del Mar Medical Research Institute), Hospital del Mar, Barcelona, Catalunya, Spain
  7. 7 Dermatology, Consorci Parc de Salut MAR de Barcelona, Barcelona, Catalunya, Spain
  8. 8 Dermatology, Hospital Clinic de Barcelona, Barcelona, Spain
  1. Correspondence to Dr Agustín Toll, Dermatology, Hospital Clinic de Barcelona, Barcelona 08036, Spain; atoll{at}


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.

  • epidermal nevus
  • urothelial cancer
  • mosaicism
  • genetic screening/counselling

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  • Contributors AG performed all the genetic analysis and designed the genetic panel, and drafted and revised the paper. EA, MG-C, LC, CF-R and BB performed the genetic analysis and revised the paper. AV and RP gathered all clinical data from the patients, and drafted and revised the paper. IH-M analysed the genetic data and revised the paper. AT implemented the study, collected the clinical data and drafted and revised the paper.

  • Funding This study was supported by the grant PI15/00236 from Fondo de Investigación Sanitaria (FIS), Instituto de Salud Carlos III FEDER, Ministerio de Economía y Competitividad, Spain, and from the “Xarxa de Bancs de tumors sponsored by Pla Director d’Oncologia de Catalunya (XBTC)

  • Competing interests None declared.

  • Patient consent for publication Obtained.

  • Ethics approval The study was approved by the clinical ethics committee of the centre and complies with the regulations of the Declaration of Helsinki, Fortaleza, Brasil 2013, and the Organic Law 15/1999 on the Protection of Personal Data. Informed consent has been obtained from patients over the age of 12 years or from parents.

  • Provenance and peer review Not commissioned; externally peer reviewed.