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Somatic mutations in kinetochore gene KNSTRN are associated with basal proliferating actinic keratoses and cutaneous squamous cell carcinoma
Author(s) -
Schmitz L.,
Grinblat B.,
Novak B.,
Hoeh A.K.,
Händschke K.,
von Dobbeler C.,
Bierhoff E.,
Szeimies R.M.,
Gambichler T.,
Torezan L.,
FestaNeto C.,
Stockfleth E.,
Dirschka T.
Publication year - 2019
Publication title -
journal of the european academy of dermatology and venereology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.655
H-Index - 107
eISSN - 1468-3083
pISSN - 0926-9959
DOI - 10.1111/jdv.15615
Subject(s) - actinic keratosis , medicine , basal cell carcinoma , mutation , gene mutation , basal cell , sanger sequencing , microbiology and biotechnology , cancer research , gene , pathology , genetics , biology
Background Mutations in kinetochore gene KNSTRN accelerate the development of cutaneous squamous cell carcinoma ( SCC ) and may correlate with different histological classifications of actinic keratosis ( AK s). Objective To determine KNSTRN gene mutation frequency in healthy skin ( HS ), actinically damaged skin ( ADS ), in AK s with different histomorphological gradings and invasive SCC s. Methods All samples were histologically evaluated. AK lesions were additionally classified according to their upwards ( AK I– III ) and downwards ( PRO I– III ) directed growth pattern. Mutation analyses of all samples were performed using the Sanger method. Results With one exception, all detected mutations in KNSTRN gene showed an alanine‐to‐glutamate substitution at codon 40 (p.Ala40Glu). p.Ala40Glu mutation was found in 6.9% (2/29) of HS , in 16.1% (5/31) of ADS , in 18.3% (20/109) of AK s and in 30.0% (9/30) of invasive SCC s. Further stratification of AK s using the common AK classification of Röwert‐Huber revealed the p.Ala40Glu mutation in 14.7% (5/43), 13.3% (4/30) and 24.4% (11/45) ( AK I, II and III ). In contrast, the new PRO classification showed a distribution of 3.6% (1/28) in PRO I, 21.7% (13/60) in PRO II and 28.6% (6/21) in PRO III . Mutation frequency in HS showed significant differences compared to AK s classified as PRO III and invasive SCC s ( P < 0.05). In contrast, there were no statistically significant differences between HS and AK s when classified according to Röwert‐Huber. Conclusions Recurrent somatic mutation p.Ala40Glu in KNSTRN gene is associated with basal proliferating AK s in accordance with invasive SCC s. This supports the impact of basal proliferative pattern in terms of progression.