DNA methylation in desmoid-type fibromatosis tumors

Background: The majority of desmoid-type fibromatosis (DTF) tumors have a mutation (S45F or T41A) in the CTNNB1 gene and a prognostic role for these mutations is proposed. The aim of this pilot study was to examine genome-wide DNA methylation profiles of S45F and T41A mutated DTF to explain differences in clinical behavior between these subtypes.Methods: Genome-wide analysis of DNA methylation was performed using MeD-seq on formalin fixed, paraffin embedded DTF samples harboring a S45F or a T41A mutation. Cluster analysis of differentially methylated regions (DMRs) was performed. Mann-Whitney U test was used to identify statistically significant differences (p1.5.Results: MeD-seq analysis was performed on 29 primary DTF tumor samples (n=15 T41A, n=14 S45F). 365 regions were identified as DMRs. Clustering analysis yielded several distinct clusters, but no clear separation was observed between the two mutation groups. Only 6 DMRs had a fold change of >1.5. A significant difference (p=0.04) in methylation (S45F vs. T41A) of the CCDC6 gene was found.Conclusions: This study identified a difference in methylation of the CCDC6 gene between the CTNNB1 mutation types of DTF, but could not identify distinct methylation patterns of S45F and T41A DTF.