Epigenetic events in ameloblastomas: immuno-expression of DNMT1, DNMT3b and H3K9ac and hMutS promoters' methylation profile

• Grant number: 17/08995-2
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: August 01, 2017
• End date: September 30, 2020
• Field of knowledge: Health Sciences - Dentistry
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Pablo Agustin Vargas
• Grantee: Gleyson Kleber do Amaral Silva
• Host Institution: Faculdade de Odontologia de Piracicaba (FOP). Universidade Estadual de Campinas (UNICAMP). Piracicaba , SP, Brazil

Abstract

Ameloblastoma is an odontogenic tumor of epithelial origin most commonly diagnosed in the world's oral pathology services. It has an incidence of 0.5 cases/million/year, with no gender preference and marked involvement of the posterior region of the gnathic bones, with emphasis on the mandible (80% of cases). Surgical removal consists of the treatment of choice, but it has a great impact on patients' quality of life. Recently, our group identified a significant reduction in the expression of hMutS proteins (hMSH2, hMSH3 and hMSH6) compared to normal human dental germs. These proteins are representatives of the base pairing error repair system (MMR system). When overexpressed, they are statistically related to the presence of the BRAF-V600E mutation. In this project, we propose the study of epigenetic events possibly related to the regulation of the expression of these proteins through the analysis of the methylation pattern of the promoters of the hMutS genes and of the histone acetylation by immunoexpression of DNA methyltransferases DNMT1 and DNMT3b and H3K9ac, In addition to PCR specific methylation of the hMutS genes in 10 samples of human dental germs and 113 samples of ameloblastomas positive or not for the BRAF-V600E mutation, subdivided into 2 blocks of TMA. At the end of the study, we intend to correlate the results in search of a better understanding of the mechanisms of control of hMutS expression in ameloblastomas and how this interferes with the occurrence of the BRAF-V600E mutation and the prognosis. (AU)

Scientific publications

(6)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DO AMARAL-SILVA, GLEYSON KLEBER; LEITE, AMANDA ALMEIDA; LINHARES ALMEIDA MARIZ, BRUNO AUGUSTO; MOREIRA, FERNANDA DOS SANTOS; LOPES, MARCIO AJUDARTE; PRADO RIBEIRO, ANA CAROLINA; SANTOS-SILVA, ALAN ROGER; ROCHA, ANDRE CAROLI; VARGAS, PABLO AGUSTIN. Metastatic Neuroblastoma to the Mandible of Children: Report of Two Cases and Critical Review of the Literature. Head and Neck Pathology, JAN 2021. (17/08995-2)

RODRIGUES-FERNANDES, CARLA ISABELLY; GONCALVES JUNIOR, ARNALDO; SOARES, CIRO DANTAS; DE LIMA MORAIS, THAYNA MELO; DO AMARAL-SILVA, GLEYSON KLEBER; FREIRE DE CARVALHO, MARIA GORETTI; DE SOUZA, LUCAS LACERDA; PIRES, FABIO RAMOA; RIBEIRO BARTHOLOMEU DOS SANTOS, TERESA CRISTINA; PEREIRA, DEBORA LIMA; et al. Oral and oropharyngeal diffuse large B-cell lymphoma and high-grade B-cell lymphoma: A clinicopathologic and prognostic study of 69 cases. ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY, v. 131, n. 4, p. 452+, APR 2021. (17/14880-3, 17/08995-2)

DO AMARAL-SILVA, GLEYSON KLEBER; FONTES PEREIRA, THAIS DOS SANTOS; ROCHA, ANDRE CAROLI; LINHARES ALMEIDA MARIZ, BRUNO AUGUSTO; PRADO-RIBEIRO, ANA CAROLINA; FONSECA, FELIPE PAIVA; GOMEZ, RICARDO SANTIAGO; VARGAS, PABLO AGUSTIN. DNA methylation status of MutS genes in ameloblastoma. ORAL DISEASES, v. 28, n. 7, p. 6-pg., 2021-04-30. (17/08995-2)

DO AMARAL-SILVA, GLEYSON KLEBER; FONTES PEREIRA, THAIS DOS SANTOS; ROCHA, ANDRE CAROLI; LINHARES ALMEIDA MARIZ, BRUNO AUGUSTO; PRADO-RIBEIRO, ANA CAROLINA; FONSECA, FELIPE PAIVA; GOMEZ, RICARDO SANTIAGO; VARGAS, PABLO AGUSTIN. DNA methylation status of MutS genes in ameloblastoma. ORAL DISEASES, APR 2021. (17/08995-2)

DO AMARAL-SILVA, GLEYSON KLEBER; DIAS, LARYSSA MOURA; LINHARES ALMEIDA MARIZ, BRUNO AUGUSTO; FONSECA, FELIPE PAIVA; CARRINHO AYROZA RANGEL, ANA LUCIA; ZANELLA, VIRGILIO GONZALES; CASTILHO, ROGERIO MORAES; MARTINS, MANOELA DOMINGUES; VARGAS, PABLO AGUSTIN; WAGNER, VIVIAN PETERSEN. MutS alpha expression predicts a lower disease-free survival in malignant salivary gland tumors: an immunohistochemical study. MEDICINA ORAL PATOLOGIA ORAL Y CIRUGIA BUCAL, v. 27, n. 2, p. 10-pg., 2022-03-01. (09/53839-2, 17/08995-2, 18/12435-5, 15/21520-8, 16/21785-4, 18/24715-2)

DO AMARAL-SILVA, GLEYSON KLEBER; LEITE, AMANDA ALMEIDA; LINHARES ALMEIDA MARIZ, BRUNO AUGUSTO; MOREIRA, FERNANDA DOS SANTOS; LOPES, MARCIO AJUDARTE; PRADO RIBEIRO, ANA CAROLINA; SANTOS-SILVA, ALAN ROGER; ROCHA, ANDRE CAROLI; VARGAS, PABLO AGUSTIN. Metastatic Neuroblastoma to the Mandible of Children: Report of Two Cases and Critical Review of the Literature. Head and Neck Pathology, v. 15, n. 3, p. 12-pg., 2021-01-04. (17/08995-2)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

SILVA, Gleyson Kleber do Amaral. Immunohistochemical analyses of DNA methyltransferases and H3K9ac, and methylation profile of the MutS genes in ameloblastomas. 2020. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Faculdade de Odontologia de Piracicaba Piracicaba, SP.