Abstract
Objectives: DNA methyltransferases (DNMTs) and the histone modification H3K9ac are epigenetic markers. This study aimed to describe the immunohistochemical expression of DNMT1, DNMT3A, DNMT3B, and H3K9ac in the dental follicle (DF), ameloblastoma (AME), and ameloblastic carcinoma (AC), correlating these expressions with the recurrence and aggressive behavior in ameloblastoma.Study Design: Immunohistochemical reactions were performed in 10 human DFs, 38 ameloblastomas, and 6 AC samples. Another 59 ameloblastomas assembled in a tissue microarray were used to compare the immunoexpression with the clinical, radiographic, and histopathological characteristics and the presence of BRAFv600e mutation. Each slide was digitized as a high-resolution image and quantified by Aperio ScanScope Nuclear V9 software. All statistical analyzes were performed using GraphPad Prism statistical software.Results: DNMT3B expression was higher in ameloblastomas than in the DFs, while the AC overexpressed all proteins. The ameloblastomas with BRAFv600e mutation, vestibular/lingual, or vestibular/palatine bone cortical disruption and maxilla involvement showed DNMT1 overexpression, while recurrent cases had high DNMT3B levels.Conclusions: DNA methylation and histone modification might play a role in the development, clinical aggressiveness, and recurrence rates of ameloblastoma, such as the progression to AC. Further investigation about gene methylations in ameloblastomas is needed to better understand its relationship with aggressiveness and recurrence.
Highlights
Epigenetic events are mechanisms responsible for controlling gene expression, playing a role in several physiological and pathological functions without altering the genome sequence [1]
Formalinfixed paraffin-embedded specimens of 10 dental follicles (DF), 38 conventional ameloblastomas (AME), and six ameloblastic carcinoma (AC) were used to compare the quantitative differences among DNMT1, DNMT3A, DNMT3B, and H3K9ac positive cells
In the DF group, high DNMT1 and DNMT3A expression were scattered in the ameloblastic epithelium, stellate reticulum, dental papilla, and connective tissue
Summary
Epigenetic events are mechanisms responsible for controlling gene expression, playing a role in several physiological and pathological functions without altering the genome sequence [1]. The methyl group transforms the cytosine in 5-methylcytosine (5mC), which ends up blocking the transcriptional machinery to engage in the gene’s promoter area, causing gene silencing This reaction is possible due to the DNA methyltransferase’s (DNMTs) catalytic activity, developed by the DNMT1, DNMT3A, and DNMT3B proteins [2,3,4]. DNMT3A and DNMT3B are responsible for creating the de novo methylation pattern and can inactivate new gene expressions [3, 5,6,7] The dynamism in this epigenetic control is possible due to the demethylation antagonist action, catalyzed by the ten-eleven translocation (TET) proteins, which removes the methyl group from the 5mC [8]
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