DNA methylation status of MutS genes in ameloblastoma

Abstract

Objectives: Ameloblastoma is an odontogenic epithelial tumour with a low expression of mismatch repair system components. We aimed to investigate the methylation status of the genes MSH2, MSH3 and MSH6 (MutS group) in conventional ameloblastomas. Materials and Methods:The ameloblastoma and dental follicle samples (n = 10 each) were collected from 20 different patients. Each ameloblastoma sample was sectioned into two fragments: one was paraffin-embedded while the other one, likewise the dental follicle samples, was fixed in RNAlater and frozen at −196°C. All frozen samples were investigated for the MutS genes methylation levels, using the enzymatic restriction digestion and quantitative real-time PCR (qPCR) assay. The ameloblastoma paraffin-embedded samples were submitted to immunohistochemical reactions for MutS proteins detection and digitally quantification. Correlation analyses were performed between the immunohistochemical results and the respective gene methylation percentage.Results: There are no significant differences between the MutS genes methylation levels in the ameloblastoma and the dental follicle. However, a strong negative correlation was found between MSH2 and MSH6 gene methylation status and their respective proteins expressions evaluated by immunohistochemistry. Conclusion:Our results show that the genes methylations is in part responsible for decreasing the expression of MSH2 and MSH6 genes in ameloblastoma.

Expression of DNMTs and H3K9ac in Ameloblastoma and Ameloblastic Carcinoma

“…Interestingly, our results suggest that among the epigenetic mechanisms evaluated, changes in DNA methylation, through DNMT activation, have a more significant role in AME growth and aggressiveness compared to histone acetylation. Moreover, DNA hypermethylation triggered by DNMT overexpression in AME could induce the silencing of important regulatory and tumor suppressor genes, such as cell cycle genes [ 22 – 24 ], apoptosis [ 25 ], matrix metalloproteinases [ 26 ], LINE-1 [ 27 ], and the mismatch repair genes MSH2 and MSH6 [ 28 ]. In AC samples, only the p16 gene was investigated and shown hipermethylation [ 22 , 29 ].…”