{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:09:13Z","timestamp":1785434953225,"version":"3.56.0"},"reference-count":40,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Bulgarian Science Fund","award":["K\u041f-06-H63\/2\/13.12.2022"],"award-info":[{"award-number":["K\u041f-06-H63\/2\/13.12.2022"]}]},{"award":["K\u041f-06-H63\/2\/13.12.2022"],"award-info":[{"award-number":["K\u041f-06-H63\/2\/13.12.2022"]}],"id":[{"id":"https:\/\/ror.org\/05eg49r29","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Reports"],"abstract":"<jats:p>Oral squamous cell carcinoma (OSCC) typically develops in individuals with established risk factors such as tobacco and alcohol use, yet an increasing number of cases occur in young non-smoking, non-drinking (NSND) patients. We report a case of oral tongue OSCC in a 33-year-old woman who is a never-smoker and never-drinker without identifiable environmental or local risk factors. The patient underwent surgical treatment followed by adjuvant radiotherapy and remains disease-free 15 months after therapy. Whole-exome sequencing (WES) revealed a pathogenic truncating TP53 mutation together with additional somatic alterations affecting genes involved in DNA repair, hypoxia adaptation, mitochondrial function, and epigenetic regulation. The heterogeneous mutational profile suggests branched tumor evolution and the involvement of non-classical tumorigenic pathways. This report contributes to the growing evidence that OSCC in young NSND patients represents a biologically distinct subgroup and demonstrates the value of comprehensive genomic profiling for improving understanding of tumor heterogeneity and potential molecular drivers in the absence of traditional carcinogenic exposures.<\/jats:p>","DOI":"10.3390\/reports9020130","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T08:08:02Z","timestamp":1777018082000},"page":"130","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Early-Onset Oral Tongue Squamous Cell Carcinoma in the Absence of Traditional Risk Factors: A Case Report with Whole-Exome Sequencing Analysis"],"prefix":"10.3390","volume":"9","author":[{"given":"Evgeniy","family":"Aleksiev","sequence":"first","affiliation":[{"name":"Research Institute of Innovative Medical Science, Medical University Sofia,  Akad. Ivan Geshov 15, 1431 Sofia, Bulgaria"},{"name":"Department of Dental, Oral and Maxillofacial Surgery, Faculty of Dental Medicine, Medical University Sofia,  Akad. Ivan Geshov 15, 1431 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darina Lyudmilova","family":"Kachakova-Yordanova","sequence":"additional","affiliation":[{"name":"Molecular Medicine Center, Department of Medical Chemistry and Biochemistry, Medical Faculty, Medical University of Sofia,  Akad. Ivan Geshov 15, 1431 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7528-590X","authenticated-orcid":false,"given":"Vanyo","family":"Mitev","sequence":"additional","affiliation":[{"name":"Research Institute of Innovative Medical Science, Medical University Sofia,  Akad. Ivan Geshov 15, 1431 Sofia, Bulgaria"},{"name":"Department of Chemistry and Biochemistry, Medical Faculty, Medical University Sofia,  Akad. Ivan Geshov 15, 1431 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin Marinov","family":"Georgiev","sequence":"additional","affiliation":[{"name":"Molecular Medicine Center, Department of Medical Chemistry and Biochemistry, Medical Faculty, Medical University of Sofia,  Akad. Ivan Geshov 15, 1431 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1748-4489","authenticated-orcid":false,"given":"Zornitsa","family":"Mihaylova","sequence":"additional","affiliation":[{"name":"Research Institute of Innovative Medical Science, Medical University Sofia,  Akad. Ivan Geshov 15, 1431 Sofia, Bulgaria"},{"name":"Department of Dental, Oral and Maxillofacial Surgery, Faculty of Dental Medicine, Medical University Sofia,  Akad. 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