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Somatic mosaicism
Short report
Keratinocytic epidermal nevi are associated with mosaic RAS mutations
  1. Christian Hafner1,
  2. Agusti Toll2,
  3. Susanne Gantner1,
  4. Andreas Mauerer1,
  5. Irene Lurkin3,
  6. Francesco Acquadro4,
  7. Alejandro Fernández-Casado2,
  8. Ellen C Zwarthoff3,
  9. Wolfgang Dietmaier5,
  10. Eulalia Baselga6,
  11. Elisabet Parera2,
  12. Asunción Vicente7,
  13. Ariel Casanova8,
  14. Juan Cigudosa4,
  15. Thomas Mentzel9,
  16. Ramon M Pujol2,
  17. Michael Landthaler1,
  18. Francisco X Real8,10
  1. 1Department of Dermatology, University of Regensburg, Regensburg, Germany
  2. 2Servei de Dermatologia, Hospital del Mar-Parc de Salut Mar, Universitat Autònoma de Barcelona, Barcelona, Spain
  3. 3Department of Pathology, Josephine Nefkens Institute, Erasmus MC, Rotterdam, The Netherlands
  4. 4Grupo de Citogenética Molecular and CIBERER, Programa de Genética del Cáncer Humano, Centro Nacional de Investigaciones Oncológicas, Madrid, Spain
  5. 5Institute of Pathology, University of Regensburg, Regensburg, Germany
  6. 6Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
  7. 7Department of Dermatology, Hospital Sant Joan de Déu, University of Barcelona, Spain
  8. 8Grupo de Carcinogénesis Epitelial, Programa de Patología Molecular, Centro Nacional de Investigaciones Oncológicas, Madrid, Spain
  9. 9Dermatopathology, Friedrichshafen, Germany
  10. 10Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain
  1. Correspondence to Dr Christian Hafner, Department of Dermatology, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany; christian.hafner{at}ukr.de

Abstract

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.

  • HRAS
  • KRAS
  • NRAS
  • mosaicism
  • epidermal nevus
  • dermatology
  • cancer: dermatological
  • academic medicine
  • cancer: urological
  • cell biology
  • genome-wide
  • other gastroenterology
  • pancreas and biliary tract

https://doi.org/10.1136/jmedgenet-2011-100637

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    Footnotes

    • CH and AT contributed equally to this study.

    • Funding This work was supported, in part, by grant HA5531/1-2 from the Deutsche Forschungsgemeinschaft to CH, grant PI04/1728 from Fondo de Investigación Sanitaria (FIS) to RMP, grants SAF2007-60860 and Consolíder ONCOBIO from Ministerio de Ciencia e Innovación (Madrid, Spain), EU-7FP grant #201663-UROMOL, and a grant from Asociación Española Contra el Cáncer to FXR. Grant Number: HA5531/1-2 PI04/1728 SAF2007-60860 EU-7FP grant #201663-UROMOL.

    • Competing interests None.

    • Ethics approval Ethics approval was provided by ethical boards of the universities of Regensburg and Barcelona.

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