Keratinocytic epidermal nevi are associated with mosaic RAS mutations

Christian Hafner, Agusti Toll, Susanne Gantner, Andreas Mauerer, Irene Lurkin, Francesco Acquadro, Alejandro Fernández-Casado, Ellen C. Zwarthoff, Wolfgang Dietmaier, Eulalia Baselga, Elisabet Parera, Asunción Vicente, Ariel Casanova, Juan Cigudosa, Thomas Mentzel, Ramon M. Pujol, Michael Landthaler, Francisco X. Real

Research output: Contribution to journalArticleResearchpeer-review

75 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)249-253
JournalJournal of Medical Genetics
Issue number4
Publication statusPublished - 1 Apr 2012


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