{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T17:30:42Z","timestamp":1790530242036,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,12,26]],"date-time":"2022-12-26T00:00:00Z","timestamp":1672012800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2019R1A5A2027588"],"award-info":[{"award-number":["2019R1A5A2027588"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS\u20102022\u201000165497"],"award-info":[{"award-number":["RS\u20102022\u201000165497"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Actinic keratosis (AK) and cutaneous squamous cell carcinoma in situ (CIS) are two of the most common precursors of cutaneous squamous cell carcinoma (cSCC). However, the genomic landscape of AK\/CIS and the drivers of cSCC progression remain to be elucidated. The aim of our study was to investigate the genomic alterations between AK\/CIS and cSCC in terms of somatic mutations and copy number alterations (CNAs). We performed targeted deep sequencing of 160 cancer\u2010related genes with a median coverage of 515\u00d7 for AK (<jats:italic>N<\/jats:italic>\u00a0=\u00a09), CIS (<jats:italic>N<\/jats:italic>\u00a0=\u00a09), cSCC lesions (<jats:italic>N<\/jats:italic>\u00a0=\u00a013), and matched germline controls from 17 patients. cSCC harboured higher abundance of total mutations, driver mutations and CNAs than AK\/CIS. Driver mutations were found in <jats:italic>TP53<\/jats:italic> (81%), <jats:italic>NOTCH1<\/jats:italic> (32%), <jats:italic>RB1<\/jats:italic> (26%) and <jats:italic>CDKN2A<\/jats:italic> (19%). All AK\/CIS and cSCC lesions (93.5%), except two, harboured <jats:italic>TP53<\/jats:italic> or <jats:italic>NOTCH1<\/jats:italic> mutations, some of which were known oncogenic mutations or reported mutations in normal skin. <jats:italic>RB1<\/jats:italic> driver mutations were found in CIS\/cSCC (36.4%) but not in AK. <jats:italic>CDKN2A<\/jats:italic> driver mutations were found more frequently in cSCC (30.8%) than in AK\/CIS (11.1%). Among recurrent (\u22653 samples) CNAs (gain in <jats:italic>MYC<\/jats:italic> and <jats:italic>PIK3CA<\/jats:italic>\/<jats:italic>SOX2<\/jats:italic>\/<jats:italic>TP63<\/jats:italic>; loss in <jats:italic>CDKN2A<\/jats:italic> and <jats:italic>RB1<\/jats:italic>), <jats:italic>MYC<\/jats:italic> (8q) gain and <jats:italic>CDKN2A<\/jats:italic> (9p) loss were more frequently detected in cSCC (30.8%) than in AK\/CIS (11.1%). Ultraviolet was responsible for the majority of somatic mutations in both AK\/CIS and cSCC. Our study revealed that AK\/CIS lesions harbour prevalent <jats:italic>TP53<\/jats:italic> or <jats:italic>NOTCH1<\/jats:italic> mutations and that additional somatic mutations and CNAs may lead to cSCC progression in AK\/CIS lesions.<\/jats:p>","DOI":"10.1111\/exd.14730","type":"journal-article","created":{"date-parts":[[2022,12,19]],"date-time":"2022-12-19T13:24:03Z","timestamp":1671456243000},"page":"447-456","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Targeted deep sequencing reveals genomic alterations of actinic keratosis\/cutaneous squamous cell carcinoma in situ and cutaneous squamous cell carcinoma"],"prefix":"10.1111","volume":"32","author":[{"given":"Yoon\u2010Seob","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Microbiology The Catholic University of Korea  Seoul Republic of Korea"},{"name":"Precision Medicine Research Center The Catholic University of Korea  Seoul Republic of Korea"},{"name":"Integrated Research Center for Genome Polymorphism The Catholic University of Korea  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung\u2010Hyun","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Biochemistry The Catholic University of Korea  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Min","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Seoul St. Mary's Hospital The Catholic University of Korea  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gyeong Sin","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Hospital Pathology, Seoul St. Mary's Hospital The Catholic University of Korea  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0576-0474","authenticated-orcid":false,"given":"Hei Sung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Incheon St. Mary's Hospital The Catholic University of Korea  Incheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee\u2010So","family":"Maeng","sequence":"additional","affiliation":[{"name":"Department of Pathology, Incheon St. Mary's Hospital The Catholic University of Korea  Incheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6943-5948","authenticated-orcid":false,"given":"Yeun\u2010Jun","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Microbiology The Catholic University of Korea  Seoul Republic of Korea"},{"name":"Precision Medicine Research Center The Catholic University of Korea  Seoul Republic of Korea"},{"name":"Integrated Research Center for Genome Polymorphism The Catholic University of Korea  Seoul Republic of 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