Uncovering the role of CRTC1-MAML2 translocation in salivary Mucoepidermoid Carcinoma: a clinicopathological, molecular and proteomic study

• Grant number: 19/26676-7
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: September 01, 2020
• End date: November 30, 2024
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Pablo Agustin Vargas
• Grantee: Maria Eduarda Pérez de Oliveira
• Host Institution: Faculdade de Odontologia de Piracicaba (FOP). Universidade Estadual de Campinas (UNICAMP). Piracicaba , SP, Brazil
• Associated scholarship(s): 21/10810-6 - Proximity-Dependent Biotinylation for the identification of interacting proteins in salivary gland cells harbouring the CRTC1-MAML2 translocation, BE.EP.DR

Abstract

Mucoepidermoid Carcinoma (MEC) is the most common malignant salivary gland tumor. The CRTC1-MAML2 translocation has been identified in about 50% of cases and is considered to be associated with better survival rates, although some authors have questioned its prognostic value. The mechanism of action of CRTC1-MAML2 translocation is complex and may influence several important pathways in tumorigeneses. Therefore, it is important to better understand how the translocation and its products affect the development of MEC to then develop efficient target therapies. The objectives of this innovative and multidisciplinary study are (1) to identify the prognostic value of CRTC1-MAML2 in a representative sample of MEC; (2) understand if the translocation influences the proteomic profile of CME; and (3) understand how key proteins identified as deregulated in patient samples influence tumour development in an in vitro model. We will initially investigate the presence of CRTC1-MAML2 and compare the survival time of Translocation-Positive (TP) and Translocation-Negative (TN) MEC patients. The proteomic profile of TP and TN cases will be determined by mass spectrometry. After bioinformatics analysis, promising protein targets that appear to be involved in tumour development and progression will be selected. We will evaluate the role of these proteins in regulating cell survival, invasion and migration and activation of signalling pathways in primary salivary gland cells in which the translocation was induced by stable transfection of the CRTC1-MAML2 vector. Thus, this research project will significantly contribute to a better understanding of the role of CRTC1-MAML2 translocation in MEC development and progression. It might contribute with new diagnosis, prognosis and therapeutical approaches. (AU)

Scientific publications

(8)

(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)

RODRIGUES LOUREDO, BRENDO VINICIUS; VARGAS, PABLO AGUSTIN; PEREZ-DE-OLIVEIRA, MARIA EDUARDA; LOPES, MARCIO AJUDARTE; KOWALSKI, LUIZ PAULO; CURADO, MARIA PAULA. Epidemiology and survival outcomes of lip, oral cavity, and oropharyngeal squamous cell carcinoma in a southeast Brazilian population. MEDICINA ORAL PATOLOGIA ORAL Y CIRUGIA BUCAL, v. 27, n. 3, p. 11-pg., 2022-05-01. (19/26676-7)

PEREZ-DE-OLIVEIRA, MARIA EDUARDA; ROBINSON, LIAM; JUNIOR, JOSE NARCISO ROSA ASSUNCAO; ABRAHAO, ALINE CORREA; ROMANACH, MARIO JOSE; PENAFORT, PAULO VICTOR MENDES; SILVA, LUAN CESAR DA; SANTOS-SILVA, ALAN ROGER; LOPES, MARCIO AJUDARTE; HEERDEN, WILLIE F. P. VAN; et al. Tongue hamartomas in pediatric patients: an international case series and literature review. ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY, v. 134, n. 6, p. 10-pg., 2022-12-03. (19/26676-7)

MARQUES, NELSON PEREIRA; PEREZ-DE-OLIVEIRA, MARIA EDUARDA; NORMANDO, ANA GABRIELA COSTA; MARQUES, NADIA CAROLINA TEIXEIRA; EPSTEIN, JOEL B.; MIGLIORATI, CESAR A.; MARTELLI JUNIOR, HERCILIO; RIBEIRO, ANA CAROLINA PRADO; ROCHA, ANDRE CAROLI; BRANDAO, THAIS BIANCA; et al. Clinical outcomes of dental implants in head and neck cancer patients: An overview. ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY, v. 136, n. 1, p. 12-pg., 2023-07-01. (19/26676-7)

OLIVEIRA, GABRIELLA ALVES QUIXABEIRA; PEREZ-DE-OLIVEIRA, MARIA EDUARDA; ROBINSON, LIAM; ALI KHURRAM, SYED; HUNTER, KEITH; SPEIGHT, PAUL M.; KOWALSKI, LUIZ PAULO; PINTO, CLOVIS ANTONIO LOPES; DE SA, RAISA SALES; MENDONCA, ELISMAURO FRANCISCO; et al. Epithelial salivary gland tumors in pediatric patients: An international collaborative study. International Journal of Pediatric Otorhinolaryngology, v. 168, p. 7-pg., 2023-03-23. (19/26676-7)

MARIA EDUARDA PÉREZ-DE-OLIVEIRA; WILLIE VAN HEERDEN; ANA CAROLINA FRAGOSO MOTTA; CARLA ISABELLY RODRIGUES-FERNANDES; MÁRIO JOSÉ ROMAÑACH; MICHELLE AGOSTINI; LUIZ ALCINO MONTEIRO GUEIROS; PABLO AGUSTIN VARGAS; MÁRCIO AJUDARTE LOPES; ANA CAROLINA PRADO RIBEIRO; et al. The need for communication between clinicians and pathologists in the context of oral and maxillofacial diseases. Brazilian Oral Research, v. 36, 2022-01-14. (19/26676-7)

DOS SANTOS, ERISON SANTANA; PEREZ-DE-OLIVEIRA, MARIA EDUARDA; COSTA NORMANDO, ANA GABRIELA; MONTEIRO GUEIROS, LUIZ ALCINO; ROGATTO, SILVIA REGINA; VARGAS, PABLO AGUSTIN; LOPES, MARCIO AJUDARTE; DA SILVA GUERRA, ELIETE NEVES; PAES LEME, ADRIANA FRANCO; SANTOS-SILVA, ALAN ROGER. Systemic conditions associated with increased risk to develop oral squamous cell carcinoma: Systematic review and meta-analysis. HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK, v. 44, n. 12, p. 13-pg., 2022-09-16. (22/04490-1, 19/09692-9, 19/26676-7)

NORMANDO, ANA GABRIELA COSTA; PEREZ-DE-OLIVEIRA, MARIA EDUARDA; SILVA GUERRA, ELIETE NEVES; LOPES, MARCIO AJUDARTE; ROCHA, ANDRE CAROLI; BRANDAO, THAIS BIANCA; PRADO-RIBEIRO, ANA CAROLINA; MONTEIRO GUEIROS, LUIZ ALCINO; EPSTEIN, JOEL B.; MIGLIORATI, CESAR AUGUSTO; et al. To extract or not extract teeth prior to head and neck radiotherapy? A systematic review and meta-analysis. SUPPORTIVE CARE IN CANCER, v. N/A, p. 15-pg., 2022-06-17. (19/09692-9, 19/26676-7, 18/02233-6)

PEREZ-DE-OLIVEIRA, MARIA EDUARDA; VAN HEERDEN, WILLIE; FRAGOSO MOTTA, ANA CAROLINA; RODRIGUES-FERNANDES, CARLA ISABELLY; ROMANACH, MARIO JOSE; AGOSTINI, MICHELLE; MONTEIRO GUEIROS, LUIZ ALCINO; VARGAS, PABLO AGUSTIN; LOPES, MARCIO AJUDARTE; PRADO RIBEIRO, ANA CAROLINA; et al. The need for communication between clinicians and pathologists in the context of oral and maxillofacial diseases. BRAZILIAN ORAL RESEARCH, v. 36, p. 10-pg., 2022-01-01. (19/26676-7)