{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,9]],"date-time":"2025-11-09T15:49:12Z","timestamp":1762703352711,"version":"build-2065373602"},"reference-count":46,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:00:00Z","timestamp":1761264000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012331","name":"LEO Fondet","doi-asserted-by":"publisher","award":["LF17026"],"award-info":[{"award-number":["LF17026"]}],"id":[{"id":"10.13039\/501100012331","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007688","name":"American University of Beirut","doi-asserted-by":"publisher","award":["100410"],"award-info":[{"award-number":["100410"]}],"id":[{"id":"10.13039\/100007688","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer and is most often caused by cumulative UV exposure. However, cSCC may also arise independently of UV exposure, on sites of sustained skin damage like chronic ulcers, scars, Recessive Dystrophic Epidermolysis Bullosa (RDEB), and inflammatory skin diseases such as hidradenitis suppurativa (HS). Little is known about non\u2010UV\u2010induced skin carcinomas. We aimed to describe the clinical, pathological, and genetic features, of non\u2010UV\u2010induced cSCC. We collected clinical and pathologic data corresponding to 31 patients with non\u2010UV\u2010induced cSCC, including 5 cSCC on HS, 4 on chronic leg ulcers and 8 on RDEB. DNA was extracted from FFPE samples and analysed using a NGS assay targeting 523 cancer genes. A comparison was performed with published genetic data obtained in non\u2010UV\u2010induced and UV\u2010induced cSCC. We found that the Tumour Mutational Burden (TMB) of non\u2010UV\u2010induced cSCC was 6\u2010times lower than the published TMB of UV\u2010induced cSCC. The predominant mutational signature was a clock\u2010wise signature. By comparing the frequency of driver mutations, we found\n                    <jats:italic>TP53<\/jats:italic>\n                    and\n                    <jats:italic>NOTCH1<\/jats:italic>\n                    to be significantly less frequently mutated than in UV\u2010mutated cSCC. Interestingly,\n                    <jats:italic>KMT2B<\/jats:italic>\n                    (a histone methyl transferase) was mutated in 11\/31 non\u2010UV\u2010induced cSCC and this proportion was significantly higher than in UV\u2010mutated cSCC. These mutations were high impact loss\u2010of\u2010function mutations. We found that knocking down\n                    <jats:italic>KMT2B<\/jats:italic>\n                    expression using siRNA did not affect cell proliferation of SCC\u201013 and A\u2010431 cell lines, however, it significantly increased cell migration\n                    <jats:italic>in vitro<\/jats:italic>\n                    . Taken together, this study provides a comprehensive description of non\u2010UV\u2010induced cSCC and identifies that\n                    <jats:italic>KMT2B<\/jats:italic>\n                    is mutated and involved in non\u2010UV\u2010induced cSCC carcinogenesis. \u00a9 2025 The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.6484","type":"journal-article","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T07:23:13Z","timestamp":1761290593000},"page":"479-490","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic landscape of non\u2010\n                    <scp>UV<\/scp>\n                    \u2010induced cutaneous squamous cell carcinomas"],"prefix":"10.1002","volume":"267","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-0479-0277","authenticated-orcid":false,"given":"Carmen","family":"Al Youssef","sequence":"first","affiliation":[{"name":"Cutaneous Biology Lab Institut Cochin, INSERM U1016, UMR 8104  Paris France"},{"name":"University Paris Cit\u00e9 Facult\u00e9 de Sant\u00e9 \u2010 UFR de M\u00e9decine  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9637-4685","authenticated-orcid":false,"given":"Mansour","family":"Alkobtawi","sequence":"additional","affiliation":[{"name":"Cutaneous Biology Lab Institut Cochin, INSERM U1016, UMR 8104  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R\u00e9mi","family":"Safi","sequence":"additional","affiliation":[{"name":"Department of Dermatology American University of Beirut  Beirut Lebanon"},{"name":"Josep Carreras Leukemia Research Institute  Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8699-6755","authenticated-orcid":false,"given":"Johan","family":"Chanal","sequence":"additional","affiliation":[{"name":"Cutaneous Biology Lab Institut Cochin, INSERM U1016, UMR 8104  Paris France"},{"name":"Department of Dermatology H\u00f4pital Cochin, AP\u2010HP Centre\u2010Universit\u00e9 Paris Cit\u00e9  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2341-6848","authenticated-orcid":false,"given":"Pierre","family":"Sohier","sequence":"additional","affiliation":[{"name":"Cutaneous Biology Lab Institut Cochin, INSERM U1016, UMR 8104  Paris France"},{"name":"Department of Pathology H\u00f4pital Cochin, AP\u2010HP Centre\u2010Universit\u00e9 Paris Cit\u00e9  Paris 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