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Ameloblastoma is an odontogenic neoplasm whose molecular pathogenesis has only recently been elucidated. The discovery of recurrent activating mutations in FGFR2, BRAF, and RAS in a large majority of ameloblastomas has implicated dysregulation of MAPK pathway signaling as a critical step in the pathogenesis of this tumor. Some degree of controversy exists regarding the role of mutations affecting the sonic hedgehog (SHH) pathway, specifically Smoothened (SMO), which have been postulated to serve as either an alternative pathogenetic mechanism or secondary mutations. Here, we review recent advances in our understanding of the molecular pathogenesis of ameloblastoma as well as the diagnostic, prognostic, and therapeutic implications of these discoveries.
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