Immunolocalization of DNMT1 and DNMT3a in Salivary Gland Neoplasms

Gomes, Carolina Cavaliéri; Oliveira, Carla da Silveira e; Pimenta, Luiz Gustavo Garcia Santos; Marco, Luiz; Gomez, Ricardo Santiago

doi:10.1159/000209391

Cited by 7 publications

(3 citation statements)

References 47 publications

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“…Few studies have analyzed the expression of DNMTs in MEC. As in the present study, Cavaliéri Gomes et al (2009) 20 also demonstrated that the nuclear expression of DNMT1 and DNMT3A was concentrated in the salivary gland tumors, whereas DNMT3A was predominantly cytoplasmic. The presence of DNMT3A and DNMT3B is associated with novel methylation in the DNA 21 .…”

Section: Discussionsupporting

confidence: 88%

DNA methyltransferase expression is associated with cell proliferation in salivary mucoepidermoid carcinoma

Guimarães

Almeida

Castilho

et al. 2020

J Oral Pathology Medicine

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Objectives The present study investigated the correlation between the expression of DNA methyltransferase (DNMT)1, DNMT3A, and DNMT3B and the proliferation of mucoepidermoid carcinomas (MECs) using the molecular markers Ki‐67 and cyclin D1. This study also demonstrates the effects of 5‐aza‐2‐deoxycytidine (5AC) on the MEC tumor cell lines in relation to DNMT1 and DNMT3A expression, and cell‐cycle arrest. Materials and Methods The immunohistochemistry of DNMT1, DNMT3A, DNMT3B, Ki‐67, and cyclin D1 was analyzed in 40 samples of MEC and 15 samples of healthy minor salivary glands. The effects of 5AC on DNMT1 and DNMT3B expression in MEC cell lines were analyzed by Western blot, and the effects of 5AC on the cell cycle were analyzed using flow cytometry. Results The expression of DNMT1 and DNMT3B was more intense in MECs than in healthy salivary glands. A strong correlation was found between the expression of the DNMTs and the proliferation markers. This correlation was validated In Vitro, where treatment with 5AC reduced the expression of the DNMTs and the percentage of cells at the G2/M phase of the cell cycle. Conclusion The expression of DNMT1, DNMT3A, DNMT3B is correlated significantly with the expression of Ki‐67 and cyclin D1. The treatment with 5AC reduces DNMT expression and decreases the percentage of cells at the G2/M phase of the cell cycle, while increasing the cells at the G0/G1 phase.

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Section: Discussionsupporting

confidence: 88%

DNA methyltransferase expression is associated with cell proliferation in salivary mucoepidermoid carcinoma

Guimarães

Almeida

Castilho

et al. 2020

J Oral Pathology Medicine

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“…To date, information about the expression of DNMT3A in SGTs remains scarce. A single study has shown that in minor SGTs, DNMT3A shows mainly nucleic distribution and that nuclear immunohistochemical staining is observed in almost 17% of ACCs [64].…”

Section: Discussionmentioning

confidence: 99%

Enhanced Transcriptional Signature and Expression of Histone-Modifying Enzymes in Salivary Gland Tumors

Manou,

Loupis,

Vrachnos

et al. 2023

Cells

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Salivary gland tumors (SGTs) are rare and complex neoplasms characterized by heterogenous histology and clinical behavior as well as resistance to systemic therapy. Tumor etiology is currently under elucidation and an interplay of genetic and epigenetic changes has been proposed to contribute to tumor development. In this work, we investigated epigenetic regulators and histone-modifying factors that may alter gene expression and participate in the pathogenesis of SGT neoplasms. We performed a detailed bioinformatic analysis on a publicly available RNA-seq dataset of 94 ACC tissues supplemented with clinical data and respective controls and generated a protein–protein interaction (PPI) network of chromatin and histone modification factors. A significant upregulation of TP53 and histone-modifying enzymes SUV39H1, EZH2, PRMT1, HDAC8, and KDM5B, along with the upregulation of DNA methyltransferase DNMT3A and ubiquitin ligase UHRF1 mRNA levels, as well as a downregulation of lysine acetyltransferase KAT2B levels, were detected in ACC tissues. The protein expression of p53, SUV39H1, EZH2, and HDAC8 was further validated in SGT tissues along with their functional deposition of the repressive histone marks H3K9me3 and H3K27me3, respectively. Overall, this study is the first to detect a network of interacting proteins affecting chromatin structure and histone modifications in salivary gland tumor cells, further providing mechanistic insights in the molecular profile of SGTs that confer to altered gene expression programs.

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“…These results corroborate with our findings, suggesting a hypermethylated profile in different oral pathologies. On the other hand, some studies have found that DNMT1 expression was similar among normal salivary gland tissue and benign and malignant salivary gland tumors [34,35]. However, Shieh et al found that mucoepidermoid carcinoma (MEC) without DNMT1 expression had longer survival rates than MEC patients with DNMT1 immunoreactivity (mean 71.9 and 31.9 months, respectively) [35].…”

Section: Discussionmentioning

confidence: 99%

Expression of DNMTs and H3K9ac in Ameloblastoma and Ameloblastic Carcinoma

Amaral‐Silva

Morais

Wagner

et al. 2021

Front. Oral. Health

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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.

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Immunolocalization of DNMT1 and DNMT3a in Salivary Gland Neoplasms

Cited by 7 publications

References 47 publications

DNA methyltransferase expression is associated with cell proliferation in salivary mucoepidermoid carcinoma

DNA methyltransferase expression is associated with cell proliferation in salivary mucoepidermoid carcinoma

Enhanced Transcriptional Signature and Expression of Histone-Modifying Enzymes in Salivary Gland Tumors

Expression of DNMTs and H3K9ac in Ameloblastoma and Ameloblastic Carcinoma

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