Keratinocytic epidermal nevi are associated with mosaic RAS mutations

Background Activating RAS mutations in the germline cause rare developmental disorders such as Costello syndrome. Somatic RAS mutations are found in approximately 30% of human cancers. Keratinocytic epidermal nevi (KEN) represent benign congenital skin lesions arranged along Blaschko's lines. A...

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Detalles Bibliográficos
Autores: Hafner, C, Toll, A, Gantner, S, Mauerer, A, Lurkin, I, Acquadro, F, Fernandez-Casado, A, Zwarthoff, EC, Dietmaier, W, Baselga, E, Parera, E, Vicente, A, Casanova, A, Cigudosa, J, Mentzel, T, Pujol, RM, Landthaler, M, Real, FX
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2012
País:España
Institución:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repositorio:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p11443
Acceso en línea:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=11443
https://epub.uni-regensburg.de/36142
Access Level:acceso abierto
Descripción
Sumario:Background Activating RAS mutations in the germline cause rare developmental disorders such as Costello syndrome. Somatic RAS mutations are found in approximately 30% of human cancers. Keratinocytic epidermal nevi (KEN) represent benign congenital skin lesions arranged along Blaschko's lines. A subgroup of KEN is caused by hotspot oncogenic FGFR3 and PIK3CA mutations in mosaicism, but the majority lack these mutations. Methods This study screened 72 KEN for activating mutations in RAS genes and other oncogenes. Results Activating RAS mutations were identified in 28/72 (39%) of KEN. HRAS was the most commonly affected oncogene (86%), with the HRAS p.G13R substitution representing a new hotspot mutation. Conclusion These results indicate that activating RAS somatic mutations leading to mosaicism result in benign KEN of the skin. Given the prevalence of KEN, mosaic HRAS mutations appear to be more common in patients than germline ones. These findings identify KEN as a mosaic RASopathy and lend further support to the notion that genetic mosaicism is an important contributor to disease.

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