title: High frequency of FGFR3 mutations in adenoid seborrheic keratoses.
abstract: FGFR3 germline mutations cause autosomal dominant skeletal disorders including achondroplasia, thanatophoric dysplasia, severe achondroplasia with developmental delay and acanthosis nigricans, and Crouzon syndrome. Somatic mutations of FGFR3 have been identified in bladder cancer, multiple myeloma, and other neoplasms. FGFR3 mutations have also been detected in 40% of seborrheic keratoses (SKs) of the hyperkeratotic and acanthotic subtype, which are very common benign skin tumors. Using a multiplex SNaPshot assay that covers 11 activating FGFR3 mutations, we investigated a series of 27 SKs of the adenoid subtype. Mutations were detected in 23 of 27 (85%) adenoid SKs. R248C mutations were the most frequent mutation type. In two SKs, the A393E mutation was found, which has not been described in acanthotic and hyperkeratotic SKs so far. Three adenoid SKs displayed two simultaneous FGFR3 mutations. Adenoid SKs seem to be characterized by a higher frequency of FGFR3 mutations than hyperkeratotic and acanthotic SKs. The mechanism for the high rate of somatic FGFR3 mutations in these benign skin tumors remains elusive, but UV light exposure may play a potential role, especially in the R248C mutations.
authors.affiliation: Department of Dermatology, University of Regensburg, Regensburg, Germany. christian.hafner@klinik.uni-regensburg.de
authors.forename: Christian
authors.initials: C
authors.lastname: Hafner
authors.forename: Johanna M M
authors.initials: JM
authors.lastname: van Oers
authors.forename: Arndt
authors.initials: A
authors.lastname: Hartmann
authors.forename: Michael
authors.initials: M
authors.lastname: Landthaler
authors.forename: Robert
authors.initials: R
authors.lastname: Stoehr
authors.forename: Hagen
authors.initials: H
authors.lastname: Blaszyk
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Hofstaedter
authors.forename: Ellen C
authors.initials: EC
authors.lastname: Zwarthoff
authors.forename: Thomas
authors.initials: T
authors.lastname: Vogt
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005787:Gene Frequency; D018095:Germ-Line Mutation; D006801:Humans; D017492:Keratosis, Seborrheic / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D051498:Receptor, Fibroblast Growth Factor, Type 3