title: Keratinocytic epidermal nevi are associated with mosaic RAS mutations.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Dermatology, University of Regensburg, Regensburg, Germany. christian.hafner@ukr.de
authors.forename: Christian
authors.initials: C
authors.lastname: Hafner
authors.forename: Agusti
authors.initials: A
authors.lastname: Toll
authors.forename: Susanne
authors.initials: S
authors.lastname: Gantner
authors.forename: Andreas
authors.initials: A
authors.lastname: Mauerer
authors.forename: Irene
authors.initials: I
authors.lastname: Lurkin
authors.forename: Francesco
authors.initials: F
authors.lastname: Acquadro
authors.forename: Alejandro
authors.initials: A
authors.lastname: Fernández-Casado
authors.forename: Ellen C
authors.initials: EC
authors.lastname: Zwarthoff
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Dietmaier
authors.forename: Eulalia
authors.initials: E
authors.lastname: Baselga
authors.forename: Elisabet
authors.initials: E
authors.lastname: Parera
authors.forename: Asunción
authors.initials: A
authors.lastname: Vicente
authors.forename: Ariel
authors.initials: A
authors.lastname: Casanova
authors.forename: Juan
authors.initials: J
authors.lastname: Cigudosa
authors.forename: Thomas
authors.initials: T
authors.lastname: Mentzel
authors.forename: Ramon M
authors.initials: RM
authors.lastname: Pujol
authors.forename: Michael
authors.initials: M
authors.lastname: Landthaler
authors.forename: Francisco X
authors.initials: FX
authors.lastname: Real
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004817:Epidermis / Q000473:pathology*; D005260:Female; D011905:Genes, ras; D006801:Humans; D015603:Keratinocytes / Q000473:pathology*; D008297:Male; D009030:Mosaicism; D009154:Mutation; D009506:Nevus / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics; D012878:Skin Neoplasms / Q000235:genetics*; D055815:Young Adult
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3