title: Low incidence of oncogenic EGFR, HRAS, and KRAS mutations in seborrheic keratosis.
abstract: Seborrheic keratosis (SK) represents a frequent epidermal skin tumor. Although lacking a malignant potential, these tumors reveal multiple oncogenic mutations. A previous study identified activating mutations in 89% of SK, particularly in FGFR3 and PIK3CA genes. The aim of this study was to identify further oncogenic mutations in human SK. Therefore, we screened for mutations in EGFR, FGFR2, PIK3R1, HRAS, KRAS, and NRAS genes using both Sanger sequencing of selected exons and a multiplex SNaPshot assay in 58 SK of 14 patients. We identified a somatic EGFR p.L858R mutation in 1 SK. Furthermore, the HRAS mutations p.G13R (2/58 SK) and p.Q61L (2/58 SK) were found. These mutations have not been described in human SK yet. In addition, 1 SK revealed the KRAS p.G12V mutation, which has already been reported in SK. No mutations were detected in FGFR2, PIK3R1, and NRAS genes. The results of this study suggest that activating mutations of EGFR, HRAS, and KRAS contribute to the pathogenesis of human SK, although at a lower frequency than FGFR3 and PIK3CA mutations. FGFR2, PIK3R1, and NRAS mutations obviously do not have a significant role in the development of SK.
authors.affiliation: *Department of Dermatology, University of Regensburg, Regensburg, Germany; †Department of Dermatology, Venereology, and Allergology, University Medical Center Mannheim, Ruprecht-Karl-University of Heidelberg, Mannheim, Germany; ‡Institute for Clinical Chemistry and Laboratory Medicine, University of Regensburg, Regensburg, Germany; and §Molecular Pathology Diagnostic Unit, Institute of Pathology, University of Regensburg, Regensburg, Germany.
authors.forename: Ivelina A
authors.initials: IA
authors.lastname: Georgieva
authors.forename: Andreas
authors.initials: A
authors.lastname: Mauerer
authors.forename: Leopold
authors.initials: L
authors.lastname: Groesser
authors.forename: Eva
authors.initials: E
authors.lastname: Herschberger
authors.forename: Charalampos
authors.initials: C
authors.lastname: Aslanidis
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Dietmaier
authors.forename: Michael
authors.initials: M
authors.lastname: Landthaler
authors.forename: Christian
authors.initials: C
authors.lastname: Hafner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D058543:Class Ia Phosphatidylinositol 3-Kinase; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D017492:Keratosis, Seborrheic / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009857:Oncogenes; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics; D018631:ras Proteins / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D058543:Class Ia Phosphatidylinositol 3-Kinase; D066246:ErbB Receptors; D019869:Phosphatidylinositol 3-Kinases; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D051497:Receptor, Fibroblast Growth Factor, Type 2; D018631:ras Proteins; C117307:KRAS protein, human; C588001:PIK3R1 protein, human; C512478:EGFR protein, human; C496353:FGFR2 protein, human; C501009:HRAS protein, human