title: Frequent activating HRAS mutations in trichilemmoma.
abstract: BACKGROUND
  Trichilemmoma is a benign follicular epithelial tumour exhibiting outer root sheath differentiation. It is associated with Cowden syndrome and naevus sebaceus (NS), but the pathogenesis of sporadic tumours is poorly understood. Recently, NS was found to be caused by postzygotic HRAS or KRAS mutations.
  
  
  OBJECTIVE
  We sought to determine whether NS-related and NS-unrelated trichilemmomas harbour RAS mutations.
  
  
  METHODS
  Formalin-fixed and paraffin-embedded blocks of 12 NS-related and 15 NS-unrelated trichilemmomas from 26 individuals were retrieved and analysed to determine the presence of mutations in exons 1 and 2 of the HRAS, KRAS and NRAS genes by polymerase chain reaction and direct sequencing. Mutational hotspots of the FGFR3 and PIK3CA genes were also analysed for NS-unrelated cases.
  
  
  RESULTS
  Among the 27 cases, mutually exclusive HRAS c.37G>C and c.182A>G mutations were observed in 17 and three tumours, respectively. Of the 12 NS-related tumours, 11 (92%) harboured the HRAS c.37G>C substitution. Of the 15 sporadic tumours, nine (60%) harboured HRAS mutations, including six c.37G>C and three c.182A>G. An HRAS c.182A>G mutation was observed only in sporadic tumours. No mutations were observed in the other genes that were tested.
  
  
  CONCLUSIONS
  The high frequency of HRAS activating mutations, including the c.182A>G substitution, which was rather rare in NS, suggests that most trichilemmomas are authentic neoplasms.
authors.affiliation: Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: J-H
authors.initials: JH
authors.lastname: Tsai
authors.forename: W-C
authors.initials: WC
authors.lastname: Huang
authors.forename: J-Y
authors.initials: JY
authors.lastname: Jhuang
authors.forename: Y-M
authors.initials: YM
authors.lastname: Jeng
authors.forename: M-L
authors.initials: ML
authors.lastname: Cheng
authors.forename: H-Y
authors.initials: HY
authors.lastname: Chiu
authors.forename: K-T
authors.initials: KT
authors.lastname: Kuo
authors.forename: J-Y
authors.initials: JY
authors.lastname: Liau
mesh_terms: D058534:Class I Phosphatidylinositol 3-Kinases; D005091:Exons / Q000235:genetics; D011905:Genes, ras / Q000235:genetics*; D005838:Genotype; D006201:Hair Diseases / Q000235:genetics; D018859:Hair Follicle; D006801:Humans; D009154:Mutation / Q000235:genetics*; D059645:Mutation Rate; D018295:Neoplasms, Basal Cell / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics; D012878:Skin Neoplasms / Q000235:genetics*
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)