FGFR3 and PIK3CA mutations in stucco keratosis and dermatosis papulosa nigra

• Published in: British journal of dermatology (1951) Vol. 162; no. 3; pp. 508 - 512
• Main Authors: Hafner, C., Landthaler, M., Mentzel, T., Vogt, T.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.03.2010; Wiley-Blackwell
• Subjects: Adult; Aged; Biological and medical sciences; Class I Phosphatidylinositol 3-Kinases; Dermatology; dermatosis papulosa nigra; DNA Mutational Analysis; Female; FGFR3; Humans; Keratosis, Seborrheic - genetics; Keratosis, Seborrheic - pathology; Male; Medical sciences; Middle Aged; Mutation; Phosphatidylinositol 3-Kinases - genetics; PIK3CA; Receptor, Fibroblast Growth Factor, Type 3 - genetics; Risk Factors; stucco keratosis; Young Adult; Skin disease; dermatosis papulosa nigra; PIK3CA; Dermatology; Mutation; FGFR3; stucco keratosis; Keratosis
• ISSN: 0007-0963; 1365-2133
• DOI: 10.1111/j.1365-2133.2009.09488.x

Summary Background  Stucco keratosis (STK) and dermatosis papulosa nigra (DPN) are referred to as variants of seborrhoeic keratosis. However, the genetic alterations involved in the pathogenesis of these benign tumours are unknown. Objectives  Because FGFR3 and PIK3CA mutations have been reported to be involved in the pathogenesis of seborrhoeic keratosis, we analysed whether these mutations are also present in STK and DPN. Methods  A SNaPshot® multiplex assay was used for analysis of 11 previously described FGFR3 hotspot mutations. PIK3CA mutations were analysed by a SNaPshot® assay covering five PIK3CA hotspot mutations. Results  Five STK and two DPN samples were analysed. Three of five STK samples revealed a PIK3CA mutation (E542K, E545K), but no FGFR3 mutation was found. In contrast, both DPN samples harboured an FGFR3 mutation (R248C, S249C) but no PIK3CA mutation. Control tissues available for three samples did not show PIK3CA or FGFR3 mutations, excluding germline mutations and indicating a strong genotype–phenotype correlation between the mutation and the lesion. Conclusions  These results indicate that FGFR3 and PIK3CA mutations are involved in the pathogenesis of STK and DPN. The molecular genetic findings furthermore support the concept that both skin lesions are specific variants of seborrhoeic keratosis, sharing a common genetic background.