{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T10:52:47Z","timestamp":1780051967943,"version":"3.53.1"},"reference-count":33,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T00:00:00Z","timestamp":1775952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Faculty of Dentistry and the Chiang Mai University Presidential Scholarship, Chiang Mai University, Thailand"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Ameloblastoma (AM) is a common locally invasive benign odontogenic tumor in Asian populations. Although fibroblast growth factor receptor 2 (FGFR2) mutations have been reported in AM, FGFR2 amplification, the predominant form of FGFR2 aberration in human cancers, remains unexplored. This study aimed to evaluate FGFR2 protein expression, FGFR2 gene copy number variations, and their associations with demographic and clinico-radio-pathological parameters in mandibular AM. Eighty-seven cases of mandibular AM and 10 dental follicle (DF) specimens were included. FGFR2 protein expression was assessed by immunohistochemistry, and gene copy number variations were analyzed using the quantitative real-time polymerase chain reaction (qPCR) technique. Clinical data, including age, gender, tumor size, radiographic features, histological subtype, and recurrence history, were examined for associations with FGFR2 alterations. FGFR2 protein overexpression was observed in 95.4% of AM cases and was not significantly associated with demographic or clinico-radio-pathological variables. FGFR2 gene amplification was detected in 52.5% of cases, while 8.2% showed gene deletion. Notably, 50.8% of cases exhibited concurrent FGFR2 amplification and overexpression, and all cases with FGFR2 gene deletion also demonstrated FGFR2 overexpression. These findings suggest that FGFR2 gene amplification and deletion may contribute to FGFR2 overexpression and play a significant role in the molecular pathogenesis of mandibular AM.<\/jats:p>","DOI":"10.3390\/ijms27083443","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T08:49:02Z","timestamp":1776070142000},"page":"3443","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Overexpression of FGFR2 in Mandibular Ameloblastoma Is Potentially Associated with Gene Amplification and Deletion"],"prefix":"10.3390","volume":"27","author":[{"given":"Nattanit","family":"Boonsong","sequence":"first","affiliation":[{"name":"PhD Program in Oral Science, Faculty of Dentistry, Chiang Mai University, Under the CMU Presidential Scholarship, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nakarin","family":"Kitkumthorn","sequence":"additional","affiliation":[{"name":"Faculty of Dentistry, Burapha University, Chonburi 20131, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7473-366X","authenticated-orcid":false,"given":"Puangwan","family":"Lapthanasupkul","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Pathology, Faculty of Dentistry, Mahidol University, Bangkok 10400, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9366-4313","authenticated-orcid":false,"given":"Kittipong","family":"Laosuwan","sequence":"additional","affiliation":[{"name":"Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wacharaporn","family":"Thosaporn","sequence":"additional","affiliation":[{"name":"Faculty of Dentistry, Nation University, Chiang Mai 50210, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jutamad","family":"Makyoo","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anak","family":"Iamaroon","sequence":"additional","affiliation":[{"name":"Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1111\/odi.12646","article-title":"Ameloblastoma: Current etiopathological concepts and management","volume":"24","author":"Effiom","year":"2017","journal-title":"Oral Dis."},{"key":"ref_2","first-page":"e27734","article-title":"Ameloblastoma: An Updated Narrative Review of an Enigmatic Tumor","volume":"14","author":"Ghai","year":"2022","journal-title":"Cureus"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1016\/j.jcms.2021.09.007","article-title":"The epidemiology and management of ameloblastomas: A European multicenter study","volume":"49","author":"Boffano","year":"2021","journal-title":"J. Cranio-Maxillofac. Surg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1111\/odi.13031","article-title":"Global incidence and profile of ameloblastoma: A systematic review and meta-analysis","volume":"26","author":"Hendra","year":"2020","journal-title":"Oral Dis."},{"key":"ref_5","first-page":"e3437","article-title":"Ameloblastoma: Management and Outcome","volume":"10","author":"Adeel","year":"2018","journal-title":"Cureus"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5517","DOI":"10.1158\/1078-0432.CCR-14-1069","article-title":"Activating FGFR2\u2013RAS\u2013BRAF Mutations in Ameloblastoma","volume":"20","author":"Brown","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.jdsr.2020.12.003","article-title":"Molecular biological findings of ameloblastoma","volume":"57","author":"Fuchigami","year":"2021","journal-title":"Jpn. Dent. Sci. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/s12943-023-01761-7","article-title":"Unleashing the potential of combining FGFR inhibitor and immune checkpoint blockade for FGF\/FGFR signaling in tumor microenvironment","volume":"22","author":"Ruan","year":"2023","journal-title":"Mol. Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"490","DOI":"10.20892\/j.issn.2095-3941.2023.0137","article-title":"Current progress in cancer treatment by targeting FGFR signaling","volume":"20","author":"Du","year":"2023","journal-title":"Cancer Biol. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1111\/cpr.12260","article-title":"Roles of FGFR in oral carcinogenesis","volume":"49","author":"Xie","year":"2016","journal-title":"Cell Prolif."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e1223","DOI":"10.1002\/ctm2.1223","article-title":"FGFR2 mutations promote endometrial cancer progression through dual engagement of EGFR and Notch signalling pathways","volume":"13","author":"Dixit","year":"2023","journal-title":"Clin. Transl. Med."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Santolla, M.F., and Maggiolini, M. (2020). The FGF\/FGFR System in Breast Cancer: Oncogenic Features and Therapeutic Perspectives. Cancers, 12.","DOI":"10.3390\/cancers12103029"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Schrumpf, T., Behrens, H.-M., Haag, J., Kr\u00fcger, S., and R\u00f6cken, C. (2022). FGFR2 overexpression and compromised survival in diffuse-type gastric cancer in a large central European cohort. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0264011"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1038\/ng.2986","article-title":"Identification of recurrent SMO and BRAF mutations in ameloblastomas","volume":"46","author":"Sweeney","year":"2014","journal-title":"Nat. Genet."},{"key":"ref_15","first-page":"S77","article-title":"High FGFR2 expression associated with gene amplification of FGFR2 in ameloblastoma: A preliminary study","volume":"43","author":"Boonsong","year":"2023","journal-title":"Mahidol Dent. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.surge.2020.06.009","article-title":"Ameloblastoma: A succinct review of the classification, genetic understanding and novel molecular targeted therapies","volume":"19","author":"Shi","year":"2021","journal-title":"Surgeon"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.3892\/ijo.2013.2081","article-title":"Fibroblast growth factors 7 and 10 are involved in ameloblastoma proliferation via the mitogen-activated protein kinase pathway","volume":"43","author":"Nakao","year":"2013","journal-title":"Int. J. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.ijom.2017.02.1061","article-title":"Expression of fibroblast growth factor receptor type 2 in primary and recurrent ameloblastoma are correlated with ameloblastoma clinic characteristics","volume":"46","author":"Tang","year":"2017","journal-title":"Int. J. Oral Maxillofac. Surg."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2488","DOI":"10.1158\/2159-8290.CD-20-1669","article-title":"FGFR2 Extracellular Domain In-Frame Deletions Are Therapeutically Targetable Genomic Alterations That Function as Oncogenic Drivers in Cholangiocarcinoma","volume":"11","author":"Cleary","year":"2021","journal-title":"Cancer Discov."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1038\/s41586-022-05066-5","article-title":"Truncated FGFR2 is a clinically actionable oncogene in multiple cancers","volume":"608","author":"Zingg","year":"2022","journal-title":"Nature"},{"key":"ref_21","first-page":"e1656","article-title":"Precision medicine: Sustained response to erdafitinib in FGFR2-mutant, multiply recurrent ameloblastoma","volume":"5","author":"Le","year":"2022","journal-title":"Cancer Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1200\/PO.20.00175","article-title":"Tumor Regression After Treatment with Lenvatinib in FGFR2-Mutated Ameloblastoma","volume":"4","author":"Weaver","year":"2020","journal-title":"JCO Precis. Oncol."},{"key":"ref_23","first-page":"233","article-title":"Cancer genomics and genetics of FGFR2 (Review)","volume":"33","author":"Katoh","year":"1992","journal-title":"Int. J. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e19137","DOI":"10.7717\/peerj.19137","article-title":"A multi-center cross-sectional investigation of BRAF V600E mutation in Ameloblastoma","volume":"13","author":"Tun","year":"2025","journal-title":"PeerJ"},{"key":"ref_25","unstructured":"El-Naggar, A.K., Chan, J.K.C., Grandis, J.R., Takata, T., and Slootweg, P.J. (2017). WHO Classcification of Haed and Neck Tumors, The International Agency for Research on Cancer (IARC). [4th ed.]."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e180","DOI":"10.1016\/j.oooo.2020.06.002","article-title":"Frequency of BRAF V600E mutation in a group of Thai patients with ameloblastomas","volume":"132","author":"Lapthanasupkul","year":"2021","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Nayak, S., Goel, M.M., Makker, A., Bhatia, V., Chandra, S., Kumar, S., and Agarwal, S.P. (2015). Fibroblast Growth Factor (FGF-2) and Its Receptors FGFR-2 and FGFR-3 May Be Putative Biomarkers of Malignant Transformation of Potentially Malignant Oral Lesions into Oral Squamous Cell Carcinoma. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0138801"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1002\/jso.22120","article-title":"Increased expression of fibroblastic growth factor receptor 2 is correlated with poor prognosis in patients with breast cancer","volume":"105","author":"Sun","year":"2012","journal-title":"J. Surg. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Srisuttee, R., Arayataweegool, A., Mahattanasakul, P., Tangjaturonrasme, N., Kerekhanjanarong, V., Keelawat, S., Mutirangura, A., and Kitkumthorn, N. (2020). Evaluation of NID2 promoter methylation for screening of Oral squamous cell carcinoma. BMC Cancer, 20.","DOI":"10.1186\/s12885-020-6692-z"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1016\/j.jmoldx.2024.06.009","article-title":"Optimization of Tumor Dissection Procedures Leads to Measurable Improvement in the Quality of Molecular Testing","volume":"26","author":"Betz","year":"2024","journal-title":"J. Mol. Diagn."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"pdb-prot4455","DOI":"10.1101\/pdb.prot4455","article-title":"Purification of nucleic acids by extraction with phenol: Chloroform","volume":"2006","author":"Sambrook","year":"2006","journal-title":"Cold Spring Harb. Protoc."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1038\/nprot.2008.73","article-title":"Analyzing real-time PCR data by the comparative CT method","volume":"3","author":"Schmittgen","year":"2008","journal-title":"Nat. Protoc."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"759","DOI":"10.3906\/sag-1710-93","article-title":"Detection of CCND1, C-MYC, and FGFR1 amplification using modified SYBR Green qPCR and FISH in breast cancer","volume":"48","author":"Azarnezhad","year":"2018","journal-title":"Turk. J. Med. Sci."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/8\/3443\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T08:56:10Z","timestamp":1776070570000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/8\/3443"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,12]]},"references-count":33,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["ijms27083443"],"URL":"https:\/\/doi.org\/10.3390\/ijms27083443","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,12]]}}}