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Their classification remains challenging due to morphological and molecular variability. In this study, we performed comprehensive molecular profiling of odontogenic lesions\u2014excluding previously analyzed ameloblastomas\u2014to identify genomic alterations that define molecular subtypes and evaluate their diagnostic significance and potential therapeutic implications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>A total of 88 odontogenic lesions were analyzed, including 25 cysts and 63 benign or malignant tumors, classified according to the 2022 5th edition of the World Health Organization (WHO) classification. Targeted next-generation sequencing (NGS) was performed to detect somatic mutations. Mutational patterns were correlated with histological subtypes and clinical parameters such as age, gender, lesion location, and recurrence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Somatic mutations were identified in 46 of 69 lesions successfully sequenced (66.7%). Among malignant tumors, genomic alterations\u2014including gene fusions and mutations\u2014were detected in 75% of cases. The highest mutation frequency was observed in OTs of epithelial origin. Notably, 11 of the 46 mutated cases harbored concurrent alterations in two genes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Molecular profiling serves as a valuable diagnostic adjunct in evaluating odontogenic tumors and cysts. Incorporating mutational analysis into routine workflows may enhance diagnostic precision, particularly in small or ambiguous biopsies, and may provide preliminary insights for future development of targeted therapeutic approaches.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical relevance<\/jats:title>\n                    <jats:p>This study highlights the diagnostic value of integrating somatic mutation analysis into the standard evaluation of odontogenic lesions and highlights its potential adjunctive role in diagnostically challenging cases and as a basis for future therapeutic investigations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00784-025-06642-5","type":"journal-article","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T10:50:29Z","timestamp":1765277429000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Integrating genotype\u2013phenotype correlations into the diagnostic workflow of odontogenic tumors and cysts: insights from a 69 lesion cohort"],"prefix":"10.1007","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0732-3617","authenticated-orcid":false,"given":"Sibel Elif","family":"G\u00fcltekin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1507-4662","authenticated-orcid":false,"given":"Burcu","family":"Tok\u00f6zl\u00fc","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3184-9579","authenticated-orcid":false,"given":"Carina","family":"Heydt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8806-4786","authenticated-orcid":false,"given":"Reinhard","family":"B\u00fcttner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,9]]},"reference":[{"issue":"1","key":"6642_CR1","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.cden.2019.08.008","volume":"64","author":"AB Rajendra Santosh","year":"2020","unstructured":"Rajendra Santosh AB, Ogle OE (2020) Odontogenic tumors. 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