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| Author(s): |
Gleyson Kleber do Amaral Silva
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | Piracicaba, SP. |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Faculdade de Odontologia de Piracicaba |
| Defense date: | 2020-11-26 |
| Examining board members: |
Pablo Agustin Vargas;
Manoela Domingues Martins;
Danyel Elias da Cruz Perez;
Jean Nunes dos Santos;
Elismauro Francisco de Mendonça
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| Advisor: | Pablo Agustin Vargas |
| Abstract | |
Ameloblastoma is a benign epithelial odontogenic tumour clinically aggressive with epigenetics alterations fewer know. In this tumour, the MSH2 and MSH6 proteins in the Mismatch repair system antimutagenic pathway are low-expressed, suggesting the occurrence of epigenetic changes. This study aims to investigate the immunohistochemical profile of the epigenetic markers involved with the DNA methylation and histones acetylation in ameloblastomas and ameloblastic carcinomas, besides to reporting the MSH2, MSH3 and MSH6 (MutS) genes methylation profile in ameloblastomas. Immunohistochemical reactions were performed for DNMT1, DNMT3A, DNMT3B and H3K9ac markers in 10 dental germs, 38 conventional ameloblastomas and six ameloblastic carcinomas, seeking to determine the comparison of expressions between groups. Then, 59 conventional ameloblastomas organized in a tissue microarray block containing clinical, pathological, genetic information and a report of recurrence, underwent the same reactions to correlate with qualitative variables. Overexpression of DNMT3B in ameloblastomas was observed in relation to dental germs (p = 0.0001), as well as increases in the expressions of DNMT1 (p = 0.0175), DNMT3A (p = 0.0113) and H3K9ac (p = 0.0004) in ameloblastic carcinomas in relation to ameloblastomas. Additionally, ameloblastomas cases that presented the BRAFV600E mutation (p = 0.0114), maxillary involvement (p = 0.0072), and the vestibular-palatine cortical bone ruptured (p = 0.0066) had an increase in DNMT1 expression, while cases with recurrences (p = 0.0477) showed DNMT3B expression increased. Ten dental follicles and 10 conventional ameloblastomas fresh samples were selected to determine the MutS genes methylation profile. The samples were subjected to quantitative analyzes of real-time PCR (qPCR) assay, using the enzymatic restriction technique. It was observed that ameloblastomas have a low percentage of methylated MutS genes, without significant difference with dental follicles (p <0.05). These results suggest that new methylated gene profiles are present in ameloblastoma, favouring their more aggressive clinical behaviour and their progression to ameloblastic carcinoma. However, the low-expression of the MSH2 and MSH6 reported in the literature does not seem to be associated with changes in the methylation profiles of their respective genes, suggesting that other mechanisms may be present (AU) | |
| FAPESP's process: | 17/08995-2 - Epigenetic events in ameloblastomas: immuno-expression of DNMT1, DNMT3b and H3K9ac and hMutS promoters' methylation profile |
| Grantee: | Gleyson Kleber do Amaral Silva |
| Support Opportunities: | Scholarships in Brazil - Doctorate |