{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T23:29:29Z","timestamp":1774049369957,"version":"3.50.1"},"reference-count":31,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Oral Pathology Medicine"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Oral lichen planus confers a 1% risk of transformation to oral squamous cell carcinoma. While prior exome sequencing studies have identified multiple genetic mutations in oral squamous cell carcinoma, mutational analyses of lichen planus\u2010derived OSCC are lacking. We sought to clarify genomic events associated with oral lichen planus transformation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using rigorous diagnostic criteria, we retrospectively identified patients with non\u2010transforming oral lichen planus (i.e., known to be non\u2010transforming with 5\u00a0years of clinical follow\u2010up; <jats:italic>n<\/jats:italic>\u00a0=\u00a017), transforming oral lichen planus (tissue marginal to oral squamous cell carcinoma, <jats:italic>n<\/jats:italic>\u00a0=\u00a09), or oral squamous cell carcinoma arising in lichen planus (<jats:italic>n<\/jats:italic>\u00a0=\u00a017). Gene mutational profiles derived from whole\u2010exome sequencing on fixed mucosal specimens were compared among the groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The four most frequently mutated genes in transforming oral lichen planus and oral squamous cell carcinoma (TP53, CELSR1, CASP8, and KMT2D) identified 12\/17 (71%) of oral squamous cell carcinomas and 5\/9 (56%) of transforming oral lichen planus but were absent in non\u2010transforming oral lichen planus. We identified other known oral squamous cell carcinoma mutations (TRRAP, OBSCN, and LRP2) but also previously unreported mutations (TENM3 and ASH1L) in lichen planus\u2010associated oral squamous cell carcinomas.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These findings suggest alterations in DNA damage response and apoptosis pathways underlie lichen planus\u2010related oral squamous cell carcinoma transformation and are supported by mutational signatures indicative of DNA damage. This study characterized patterns of mutational events present in oral lichen planus associated with squamous cell carcinoma and in squamous cell carcinoma associated with oral lichen planus but not in non\u2010transforming oral lichen planus.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jop.13284","type":"journal-article","created":{"date-parts":[[2022,2,11]],"date-time":"2022-02-11T05:23:10Z","timestamp":1644556990000},"page":"395-404","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Whole\u2010exome sequencing of transforming oral lichen planus reveals mutations in DNA damage repair and apoptosis pathway genes"],"prefix":"10.1111","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5524-2750","authenticated-orcid":false,"given":"Fangyi","family":"Xie","sequence":"first","affiliation":[{"name":"Department of Dermatology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Casey A.","family":"Gleue","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Deschaine","sequence":"additional","affiliation":[{"name":"Department of Dermatology Florida State University  Tallahassee Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Surendra","family":"Dasari","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences Mayo Clinic  Rochester Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie S.","family":"Lau","sequence":"additional","affiliation":[{"name":"Medical Genome Facility Mayo Clinic  Rochester Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julio C.","family":"Sartori\u2010Valinotti","sequence":"additional","affiliation":[{"name":"Department of Dermatology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Meves","sequence":"additional","affiliation":[{"name":"Department of Dermatology Mayo Clinic  Rochester Minnesota USA"},{"name":"Department of Biochemistry and Molecular Biology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia S.","family":"Lehman","sequence":"additional","affiliation":[{"name":"Department of Dermatology Mayo Clinic  Rochester Minnesota USA"},{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,3]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/odi.13323"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/ijd.14215"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2003.08.001"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/odi.13704"},{"key":"e_1_2_11_6_1","first-page":"3","article-title":"An appraisal of highest quality studies reporting malignant transformation of oral lichen planus based on a systematic review","volume":"3","author":"Gonzalez\u2010Moles MA","year":"2020","journal-title":"Oral Dis"},{"key":"e_1_2_11_7_1","first-page":"25","article-title":"Oral lichen planus has a very low malignant transformation rate: a systematic review and meta\u2010analysis using strict diagnostic and inclusion criteria","volume":"25","author":"Idrees M","year":"2020","journal-title":"J Oral Pathol Med"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-0825.2008.01441.x"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2020.104688"},{"key":"e_1_2_11_10_1","first-page":"54","article-title":"Molecular markers as an indicator in the malignant potential of oral lichen planus: a systematic review","volume":"6","author":"Atai Z","year":"2017","journal-title":"J. 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