L Schmitz1, B Grinblat2, B Novak3, A-K Hoeh4, K Händschke4, C von Dobbeler4, E Bierhoff5, R-M Szeimies6, T Gambichler1, L Torezan2, C Festa-Neto2, E Stockfleth1, T Dirschka4,7. 1. Department of Dermatology, Faculty of Medicine, Ruhr University Bochum, Bochum, Germany. 2. Department of Dermatology, Hospital das Clínicas, University of São Paulo, São Paulo, SP, Brazil. 3. Department of Animal Physiology, Ruhr-University, Bochum, Germany. 4. CentroDerm GmbH, Wuppertal, Germany. 5. Heinz-Werner-Seifert-Institute of Dermatopathology, Bonn, Germany. 6. Department of Dermatology and Allergology, Vest Hospital, Academic Teaching Hospital University of Bochum, Recklinghausen, Germany. 7. Faculty of Health, University Witten-Herdecke, Witten, Germany.
Abstract
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 (AKs). OBJECTIVE: To determine KNSTRN gene mutation frequency in healthy skin (HS), actinically damaged skin (ADS), in AKs with different histomorphological gradings and invasive SCCs. 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 AKs and in 30.0% (9/30) of invasive SCCs. Further stratification of AKs 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 AKs classified as PRO III and invasive SCCs (P < 0.05). In contrast, there were no statistically significant differences between HS and AKs when classified according to Röwert-Huber. CONCLUSIONS: Recurrent somatic mutation p.Ala40Glu in KNSTRN gene is associated with basal proliferating AKs in accordance with invasive SCCs. This supports the impact of basal proliferative pattern in terms of progression.
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 (AKs). OBJECTIVE: To determine KNSTRN gene mutation frequency in healthy skin (HS), actinically damaged skin (ADS), in AKs with different histomorphological gradings and invasive SCCs. 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 AKs and in 30.0% (9/30) of invasive SCCs. Further stratification of AKs 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 AKs classified as PRO III and invasive SCCs (P < 0.05). In contrast, there were no statistically significant differences between HS and AKs when classified according to Röwert-Huber. CONCLUSIONS: Recurrent somatic mutation p.Ala40Glu in KNSTRN gene is associated with basal proliferating AKs in accordance with invasive SCCs. This supports the impact of basal proliferative pattern in terms of progression.
Authors: Fengying Du; Han Li; Yan Li; Yang Liu; Xinyu Li; Ningning Dang; Qingqing Chu; Jianjun Yan; Zhen Fang; Hao Wu; Zihao Zhang; Xingyu Zhu; Xiaokang Li Journal: Front Cell Dev Biol Date: 2021-12-21
Authors: Matthew L Hedberg; Corbett T Berry; Ata S Moshiri; Yan Xiang; Christopher J Yeh; Cem Attilasoy; Brian C Capell; John T Seykora Journal: Int J Mol Sci Date: 2022-03-23 Impact factor: 5.923