{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T12:04:53Z","timestamp":1768565093061,"version":"3.49.0"},"posted":{"date-parts":[[2023,12,17]]},"group-title":"Oncology","reference-count":68,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,12,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>The incidence of the mobile tongue cancer in young patients has been rising. This oral cancer (OC) type has no identified risk factors (NIRF), no established molecular markers and is not yet recognized as a distinct clinical entity.<\/jats:p>\n                <jats:p>To understand this emerging malignancy, we innovatively analyzed the public head and neck cancer multi-omics data. We identified mutational signatures that successfully stratified 307 OC and 109 laryngeal cancer cases according to their clinico-pathological characteristics. The NIRF OCs exhibited significantly increased activities of endogenous clock-like and APOBEC-associated mutagenesis, alongside specific cancer driver gene mutations, distinct methylome patterns and prominent antimicrobial transcriptomic responses. Furthermore, we show that mutational signature SBS16 in OCs reflects the combined effects of alcohol drinking and tobacco smoking.<\/jats:p>\n                <jats:p>Our study characterizes the unique disease histories and molecular programs of the NIRF OCs revealing that this emerging cancer subtype is likely driven by increased endogenous mutagenesis correlated with responses to microbial insults.<\/jats:p>","DOI":"10.1101\/2023.12.15.23299866","type":"posted-content","created":{"date-parts":[[2023,12,17]],"date-time":"2023-12-17T10:25:11Z","timestamp":1702808711000},"source":"Crossref","is-referenced-by-count":6,"title":["Molecular landscapes of oral cancers of unknown etiology"],"prefix":"10.64898","author":[{"given":"Sophie","family":"Deneuve","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B\u00e9atrice","family":"Fervers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergey","family":"Senkin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liacine","family":"Bouaoun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olivia","family":"P\u00e9rol","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B\u00e9r\u00e9nice","family":"Chavanel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingeng","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabelle","family":"Coste","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toufic","family":"Renno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiri","family":"Zavadil","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7570-1088","authenticated-orcid":false,"given":"Fran\u00e7ois","family":"Virard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023122007400601000_2023.12.15.23299866v1.1","unstructured":"GLOBOCAN Cancer Incidence, Mortality, and Prevalence Worldwide. https:\/\/gco.iarc.fr\/ (2020)."},{"key":"2023122007400601000_2023.12.15.23299866v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)60728-X"},{"key":"2023122007400601000_2023.12.15.23299866v1.3","first-page":"1","article-title":"Head and neck squamous cell carcinoma","volume":"6","year":"2020","journal-title":"Nat Rev Dis Primers"},{"key":"2023122007400601000_2023.12.15.23299866v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2014.11.011"},{"key":"2023122007400601000_2023.12.15.23299866v1.5","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1002\/cam4.4539","article-title":"Trends in the incidence of head and neck cancer by subsite between 1993 and 2015 in Japan","volume":"11","year":"2022","journal-title":"Cancer Med"},{"key":"2023122007400601000_2023.12.15.23299866v1.6","doi-asserted-by":"crossref","first-page":"104875","DOI":"10.1016\/j.oraloncology.2020.104875","article-title":"The incidence of squamous cell carcinoma of the oral tongue is rising in young non-smoking women: An international multi-institutional analysis","volume":"110","year":"2020","journal-title":"Oral Oncol"},{"key":"2023122007400601000_2023.12.15.23299866v1.7","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1002\/ijc.33896","article-title":"Diverging incidence trends of oral tongue cancer compared to other head and neck cancers in young adults in France","volume":"150","year":"2022","journal-title":"International Journal of Cancer"},{"key":"2023122007400601000_2023.12.15.23299866v1.8","doi-asserted-by":"publisher","DOI":"10.1002\/hed.24589"},{"key":"2023122007400601000_2023.12.15.23299866v1.9","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.oraloncology.2017.02.019","article-title":"Rising incidence of oral tongue cancer among white men and women in the United States, 1973-2012","volume":"67","year":"2017","journal-title":"Oral Oncol"},{"key":"2023122007400601000_2023.12.15.23299866v1.10","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.31.7883"},{"key":"2023122007400601000_2023.12.15.23299866v1.11","doi-asserted-by":"crossref","unstructured":"Dahlstrom, K. 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