Molecular and genetic aspects of odontogenic lesions

Abstract

In this article we outline the molecular findings of select odontogenic tumors. In each section, we briefly review selected the clinicoradiographic, histologic, immunologic features, focusing on the molecular findings and their applications in practice. The understanding of molecular pathobiology at various other organ sites has developed quite rapidly in recent years, however much remains unknown about the genetic profile of odontogenic tumors. Improved understanding of mutations in odontogenic tumors may clarify classification schema and elucidate targets for novel therapies. Molecular testing will no doubt improve our understanding of odontogenic tumor pathogenesis and will likely be, someday, an important component of routine clinical practice and its role will only increase in the coming years.

Fig. 1

Reprinted by permission from Macmillan Publishers Ltd: Nature Genetics, Sweeney et al. [12]. a Ameloblastoma mutation status for four genes correlated with histology and site. b Graphical representation of ameloblastoma distribution and tumor mutation

Fig. 2

Clear cell odontogenic carcinoma. a Aggressive tumor presenting as an ill-defined radiolucency of the mandible, b cross section of fresh resection specimen, c H&E, ×20; cords and nests of cell in a hyalinized stroma. Focal peripheral palisading is seen (arrow). d Fluorescence in situ hybridization dual-color break apart probe indicated the presence of EWSR1 (22q12) gene rearrangement in clear cell odontogenic carcinoma by the split red and green color signal

Fig. 3

a PTCH1 is a transmembrane receptor which inhibits SMO in the absence of Shh. b Binding of Shh to PTCH1 releases the inhibitory effect on SMO, activating the Shh pathway and associated downstream targets. During embryogenesis, this leads to growth and patterning of the limbs and of various tissues. c Mutation of PTCH1 results in loss of SMO inhibition. Tumorigenesis appears to result from constitutive activation of Shh-related proteins such as Gli1, Gli2, Gli3, and Wnt