Abstract
Ameloblastoma is the most common benign odontogenic neoplasm, but with an aggressive behavior and a high recurrence rate. Nowadays wide surgical resection is the current recommended treatment, which can cause further loss of function and esthetics. Recent studies point to the stem/progenitor cells as both initiators and propagators of the tumors. Elucidation of the cellular and molecular mechanisms underlying the tumor stem cells is of broad interest for understanding tumorigenesis and for developing effective targeted therapies. SRY related HMG box gene 2 (SOX2) is a transcription factor that plays important roles in development, stem cell renewal, and cancer formation. Few studies have revealed increased SOX2 expression in atypical ameloblastoma and ameloblastic carcinoma. For the development of personalized medicine for ameloblastoma, biomarkers that provide prognostic or predictive information regarding a tumor’s nature or its response to treatment are essential. Thus, in this study, we aimed to study if SOX2-positive cells exist in ameloblastomas and their correlation with the clinicopathologic parameters. Our data suggested BRAF(V600E) mutation might contribute to the expansion of SOX2-positive cells. The identification of BRAF(V600E) mutation and the amplification of SOX2-positive cells in ameloblastomas imply the possible benefit of applying BRAF and SOX2 inhibitors in recurrent and un-resectable ameloblastomas.
Highlights
Ameloblastoma is the most common odontogenic neoplasm, but with a high recurrence rate
We demonstrated that knockdown of SRY related HMG box gene 2 (SOX2) leads to decreased viability of ameloblastoma cells, and increased expression of SOX2 was associated with resistance to anti-BRAF small molecule inhibitors, vemurafenib and dabrafenib, in ameloblastoma cells
We first examined the expression patterns of SOX2 using two different antibodies, which have been used in the literature [29,30], in 15 ameloblastoma cases
Summary
Ameloblastoma is the most common odontogenic neoplasm, but with a high recurrence rate. Ameloblastomas are divided into three subtypes by WHO classification of tumors [1], namely, solid/multicystic type (AM-S/M), extraosseous/peripheral type, and unicystic type. These subtypes differ in clinicoradiographic presentations and prognosis. The AM-S/M tends to infiltrate in between cancellous bone trabeculae beyond the radiographical margin, and this feature leads to high recurrence rate if adequate surgical margins are not acquired [1]. Recent advances of molecular biology unraveled that recurrent BRAF(V600E) activating mutation is the most common genetic aberration in ameloblastomas [3,4,5], the detailed tumorigenic molecular mechanism is yet to be fully elucidated
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