Epigenetic similarity between adenoid ameloblastoma and dentinogenic ghost cell tumour: DNA methylation analysis in odontogenic tumours

Abstract Although adenoid ameloblastoma (AA) has recently been included in the WHO classification as a separate tumour type, its clinical, histological, immunohistochemical, and molecular similarities to dentinogenic ghost cell tumour (DGCT) raise questions about the current classification system. The aim of this study was to investigate the epigenetic similarity between AA and DGCT. A total of 35 odontogenic tumours consisting of 6 types, including 3 AAs and 4 DGCTs, were collected for this study. DNA methylation analysis was performed using the Infinium MethylationEPIC v2.0 BeadChip. Unsupervised clustering analysis was performed using t ‐distributed stochastic neighbour embedding ( t ‐SNE) and Uniform Manifold Approximation and Projection (UMAP). No differentially methylated regions were identified between AA and DGCT. Both t ‐SNE and UMAP plots demonstrated that AAs clustered together with DGCTs, clearly separated from the other types of odontogenic tumour. Within the AA and DGCT methylation class, no subclasses were identified by the presence of the so‐called AA‐like histology, characterised by cribriform architecture and duct‐like structures. These findings suggest a clear epigenetic similarity between AA and DGCT, further supporting the notion that the two tumours represent a spectrum of the same entity and may be better classified on a molecular basis as ‘WNT pathway‐altered odontogenic tumours’.