{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:12:03Z","timestamp":1791994323996,"version":"4.4.0"},"reference-count":20,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2019,5,8]],"date-time":"2019-05-08T00:00:00Z","timestamp":1557273600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100009754","name":"Galderma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009754","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acad Dermatol Venereol"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Mutations in kinetochore gene <jats:styled-content style=\"fixed-case\">KNSTRN<\/jats:styled-content> accelerate the development of cutaneous squamous cell carcinoma (<jats:styled-content style=\"fixed-case\">SCC<\/jats:styled-content>) and may correlate with different histological classifications of actinic keratosis (<jats:styled-content style=\"fixed-case\">AK<\/jats:styled-content>s).<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To determine <jats:styled-content style=\"fixed-case\">KNSTRN<\/jats:styled-content> gene mutation frequency in healthy skin (<jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content>), actinically damaged skin (<jats:styled-content style=\"fixed-case\">ADS<\/jats:styled-content>), in <jats:styled-content style=\"fixed-case\">AK<\/jats:styled-content>s with different histomorphological gradings and invasive <jats:styled-content style=\"fixed-case\">SCC<\/jats:styled-content>s.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>All samples were histologically evaluated. <jats:styled-content style=\"fixed-case\">AK<\/jats:styled-content> lesions were additionally classified according to their upwards (<jats:styled-content style=\"fixed-case\">AK<\/jats:styled-content> I\u2013<jats:styled-content style=\"fixed-case\">III<\/jats:styled-content>) and downwards (<jats:styled-content style=\"fixed-case\">PRO<\/jats:styled-content> I\u2013<jats:styled-content style=\"fixed-case\">III<\/jats:styled-content>) directed growth pattern. Mutation analyses of all samples were performed using the Sanger method.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>With one exception, all detected mutations in <jats:styled-content style=\"fixed-case\">KNSTRN<\/jats:styled-content> gene showed an alanine\u2010to\u2010glutamate substitution at codon 40 (p.Ala40Glu). p.Ala40Glu mutation was found in 6.9% (2\/29) of <jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content>, in 16.1% (5\/31) of <jats:styled-content style=\"fixed-case\">ADS<\/jats:styled-content>, in 18.3% (20\/109) of <jats:styled-content style=\"fixed-case\">AK<\/jats:styled-content>s and in 30.0% (9\/30) of invasive <jats:styled-content style=\"fixed-case\">SCC<\/jats:styled-content>s. Further stratification of <jats:styled-content style=\"fixed-case\">AK<\/jats:styled-content>s using the common <jats:styled-content style=\"fixed-case\">AK<\/jats:styled-content> classification of R\u00f6wert\u2010Huber revealed the p.Ala40Glu mutation in 14.7% (5\/43), 13.3% (4\/30) and 24.4% (11\/45) (<jats:styled-content style=\"fixed-case\">AK<\/jats:styled-content> I, <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">III<\/jats:styled-content>). In contrast, the new <jats:styled-content style=\"fixed-case\">PRO<\/jats:styled-content> classification showed a distribution of 3.6% (1\/28) in <jats:styled-content style=\"fixed-case\">PRO<\/jats:styled-content> I, 21.7% (13\/60) in <jats:styled-content style=\"fixed-case\">PRO II<\/jats:styled-content> and 28.6% (6\/21) in <jats:styled-content style=\"fixed-case\">PRO III<\/jats:styled-content>. Mutation frequency in <jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content> showed significant differences compared to <jats:styled-content style=\"fixed-case\">AK<\/jats:styled-content>s classified as <jats:styled-content style=\"fixed-case\">PRO III<\/jats:styled-content> and invasive <jats:styled-content style=\"fixed-case\">SCC<\/jats:styled-content>s (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). In contrast, there were no statistically significant differences between <jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">AK<\/jats:styled-content>s when classified according to R\u00f6wert\u2010Huber.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Recurrent somatic mutation p.Ala40Glu in <jats:styled-content style=\"fixed-case\">KNSTRN<\/jats:styled-content> gene is associated with basal proliferating <jats:styled-content style=\"fixed-case\">AK<\/jats:styled-content>s in accordance with invasive <jats:styled-content style=\"fixed-case\">SCC<\/jats:styled-content>s. This supports the impact of basal proliferative pattern in terms of progression.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdv.15615","type":"journal-article","created":{"date-parts":[[2019,4,12]],"date-time":"2019-04-12T01:03:58Z","timestamp":1555031038000},"page":"1535-1540","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Somatic mutations in kinetochore gene <scp>KNSTRN<\/scp> are associated with basal proliferating actinic keratoses and cutaneous squamous cell carcinoma"],"prefix":"10.1111","volume":"33","author":[{"given":"L.","family":"Schmitz","sequence":"first","affiliation":[{"name":"Department of Dermatology Faculty of Medicine Ruhr University Bochum Bochum Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Grinblat","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Hospital das Cl\u00ednicas University of S\u00e3o Paulo S\u00e3o Paulo SP 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