title: Activating HRAS mutation in agminated Spitz nevi arising in a nevus spilus.
abstract: OBJECTIVE
  Spitz nevi are benign melanocytic proliferations that can sometimes be clinically and histopathologically difficult to distinguish from melanoma. Agminated Spitz nevi have been reported to arise spontaneously, in association with an underlying nevus spilus, or after radiation or chemotherapy. However, to our knowledge, the genetic mechanism for this eruption has not been described.
  
  
  METHODS
  We report a case of agminated Spitz nevi arising in a nevus spilus and use exome sequencing to identify a clonal activating point mutation in HRAS (GenBank 3265) (c.37G→C) in the Spitz nevi and underlying nevus spilus. We also identify a secondary copy number increase involving HRAS on chromosome 11p, which occurs during the development of the Spitz nevi.
  
  
  CONCLUSIONS
  Our results reveal an activating HRAS mutation in a nevus spilus that predisposes to the formation of Spitz nevi. In addition, we demonstrate a copy number increase in HRAS as a "second hit" during the formation of agminated Spitz nevi, which suggests that both multiple Spitz nevi and solitary Spitz nevi may arise through similar molecular pathways. In addition, we describe a unique investigative approach for the discovery of genetic alterations in Spitz nevi.
authors.affiliation: Department of Dermatology, Stanford University School of Medicine, Stanford, California.
authors.forename: Kavita Y
authors.initials: KY
authors.lastname: Sarin
authors.forename: Bryan K
authors.initials: BK
authors.lastname: Sun
authors.forename: Charles D
authors.initials: CD
authors.lastname: Bangs
authors.forename: Athena
authors.initials: A
authors.lastname: Cherry
authors.forename: Susan M
authors.initials: SM
authors.lastname: Swetter
authors.forename: Jinah
authors.initials: J
authors.lastname: Kim
authors.forename: Paul A
authors.initials: PA
authors.lastname: Khavari
mesh_terms: D000328:Adult; D006801:Humans; D008297:Male; D018332:Nevus, Epithelioid and Spindle Cell / Q000235:genetics / Q000473:pathology*; D009508:Nevus, Pigmented / Q000235:genetics / Q000473:pathology*; D017354:Point Mutation; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics / Q000473:pathology*
chemical_list: C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)