Genomic alterations in the malignant transformation of the Pleomorphic Adenoma

• Grant number: 19/09419-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: January 01, 2021
• End date: January 31, 2024
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Fernanda Viviane Mariano Brum Corrêa
• Grantee: João Figueira Scarini
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 15/07304-0 - Study of genetic and metabolic changes of pleomorphic adenoma and carcinoma ex pleomorphic adenoma by exome, gene expression and immunohistochemistry, AP.JP
• Associated scholarship(s): 21/12567-1 - Validation of potential genomic alterations found during the malignant transformation of the pleomorphic adenoma, BE.EP.DR

Abstract

Among the tumors that can affect the salivary glands, two entities constitute interesting models for the study of the mechanism of malignant transformation. The first one, the most common benign tumor in the salivary gland, Pleomorphic Adenoma (PA), may undergo genetic transformations resulting in its malignant counterpart, Carcinoma Ex Pleomorphic Adenoma (CXPA). The latter is a rare and aggressive neoplasm, with metastasis and death in a large percentage of the cases. Although both tumors present important findings from a genetic point of view, the alterations found are focal and in specific gene sites, leaving many doubts about diagnostic markers, pathogenesis, and target therapy of PA and CXPA. In this project, we will study a group of PA and CXPA (subdivided as to the histological type and degree of progression) through the complete sequencing of the exome (Whole Exome Sequencing - WES) and we will complement the findings with previous results of our group that was performed with the CGH-array technique. In this way, we hope to expand individual genetic knowledge about PA and CXPA and still be able to compare not only the changes in the number of copies and mutations acquired in the benign counterpart and which are preserved in the carcinoma but also the particular changes to the malignant tumor. Furthermore, by analyzing genetic alterations related to PA tumorigenesis and CXPA tumor progression, we intend to add significant knowledge to what is currently known about these tumors and also to be able to provide information on diagnostic markers, pathogenesis, and target therapy, which will later be reflected in instruments for clinical application and prognostic improvement of patients affected by these neoplasms. (AU)

Scientific publications

(17)

(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)

DE ANGELIS, CAMILA MATSUNAGA; DE LIMA-SOUZA, REYDSON ALCIDES; SCARINI, JOAO FIGUEIRA; ABU EGAL, ERIKA SAID; DO AMARAL-SILVA, GLEYSON KLEBER; GONDAK, ROGERIO DE OLIVEIRA; DE ALMEIDA, OSLEI PAES; CHONE, CARLOS TAKAHIRO; KOWALSKI, LUIZ PAULO; ALTEMANI, ALBINA; et al. Immunohistochemical Expression of Fatty Acid Synthase (FASN) is Correlated to Tumor Aggressiveness and Cellular Differentiation in Salivary Gland Carcinomas. Head and Neck Pathology, APR 2021. (15/07304-0, 19/09419-0)

DE LIMA-SOUZA, REYDSON ALCIDES; SCARINI, JOAO FIGUEIRA; LAVAREZE, LUCCAS; DOMINGUES, ROMENIA RAMOS; LEME, ADRIANA FRANCO PAES; ABU EGAL, ERIKA SAID; ALTEMANI, ALBINA; MARIANO, FERNANDA VIVIANE. Malignant phenotype acquisition in pleomorphic adenoma: An exclusive proteins analysis. ORAL DISEASES, v. N/A, p. 4-pg., 2023-01-20. (19/09419-0, 15/07304-0, 20/08431-4)

LAVAREZE, LUCCAS; SCARINI, JO AO FIGUEIRA; DE LIMA-SOUZA, REYDSON ALCIDES; EMERICK, CAROLINA; DE SA, RAISA SALES; AQUINO, IARA GONCALVES; FERNANDES, PATRICIA MARIA; GONCALVES, MAYARA TREVIZOL; HELMS, MY N.; ALTEMANI, ALBINA; et al. Salivary gland cancer in the setting of tumor microenvironment: Translational routes for therapy. CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY, v. 171, p. 10-pg., 2022-03-01. (19/06809-2, 15/07304-0, 19/09419-0)

SCARINI, JOAO FIGUEIRA; LAVAREZE, LUCCAS; DE LIMA-SOUZA, REYDSON ALCIDES; EMERICK, CAROLINA; GONCALVES, MAYARA TREVIZOL; FIGUEIREDO-MACIEL, TAYNA; VIEIRA, GUSTAVO DE SOUZA; KIMURA, TALITA DE CARVALHO; DE SA, RAISA SALES; AQUINO, IARA GONCALVES; et al. Head and neck squamous cell carcinoma: Exploring frontiers of combinatorial approaches with tyrosine kinase inhibitors and immune checkpoint therapy. CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY, v. 180, p. 14-pg., 2022-12-01. (15/07304-0, 21/12567-1, 19/09419-0, 19/06809-2)

DOS SANTOS, ERISON SANTANA; NORMANDO, ANA GABRIELA COSTA; SCARINI, JOAO FIGUEIRA; CRESCENCIO, LIVIA RAMALHO; DE LIMA-SOUZA, REYDSON ALCIDES; MARIANO, FERNANDA VIVIANE; LEME, ADRIANA FRANCO PAES. Diagnostic and prognostic value of miRNAs on salivary gland tumors: a systematic review and meta-analysis. ORAL AND MAXILLOFACIAL SURGERY-HEIDELBERG, v. 25, n. 4, p. 12-pg., 2021-03-05. (18/19922-9, 19/09692-9, 19/09419-0, 19/06809-2)

LAVAREZE, LUCCAS; SCARINI, JOAO FIGUEIRA; LIMA-SOUZA, REYDSON ALCIDES DE; EGAL, ERIKA SAID ABU; TETZNER, DIEGO; LEITE, AMANDA ALMEIDA; VARGAS, PABLO AGUSTIN; ALTEMANI, ALBINA; MARIANO, FERNANDA VIVIANE. Granulomatous gingival enlargement in a patient with an unrecognized HIV infection. JOURNAL OF THE AMERICAN DENTAL ASSOCIATION, v. 154, n. 7, p. 5-pg., 2023-07-01. (15/07304-0, 19/06809-2, 19/09419-0)

DE LIMA-SOUZA, REYDSON ALCIDES; SCARINI, JOAO FIGUEIRA; LAVAREZE, LUCCAS; EMERICK, CAROLINA; DOS SANTOS, ERISON SANTANA; PAES LEME, ADRIANA FRANCO; ABU EGAL, ERIKA SAID; ALTEMANI, ALBINA; MARIANO, FERNANDA VIVIANE. Protein markers of primary salivary gland tumors: A systematic review of proteomic profiling studies. ARCHIVES OF ORAL BIOLOGY, v. 136, p. 13-pg., 2022-02-15. (19/06809-2, 18/19922-9, 19/09419-0, 15/07304-0)

DOS SANTOS, ERISON SANTANA; NORMANDO, ANA GABRIELA COSTA; SCARINI, JOAO FIGUEIRA; CRESCENCIO, LIVIA RAMALHO; DE LIMA-SOUZA, REYDSON ALCIDES; MARIANO, FERNANDA VIVIANE; LEME, ADRIANA FRANCO PAES. Diagnostic and prognostic value of miRNAs on salivary gland tumors: a systematic review and meta-analysis. ORAL AND MAXILLOFACIAL SURGERY-HEIDELBERG, MAR 2021. (19/09692-9, 19/06809-2, 19/09419-0, 18/19922-9)

DE LIMA-SOUZA, REYDSON ALCIDES; RODRIGUES, NATALIA DE MAGALHAES; SCARINI, JOAO FIGUEIRA; SOBRAL SILVA, MARIO FERNANDEZ; TINCANI, ALFIO JOSE; ABU EGAL, ERIKA SAID; ALTEMANI, ALBINA; MARIANO, FERNANDA VIVIANE. Metabolic alterations in carcinoma ex pleomorphic adenoma development of lacrimal glands. INTERNATIONAL OPHTHALMOLOGY, NOV 2021. (19/06809-2, 19/10788-0, 15/07304-0, 19/09419-0)

SCARINI, JOAO FIGURIRA; ALMEIDA MARIZ, BRUNO AUGESTO LINHARES; DE LIMA-SOUZA, REYDSON ALCIDES; LAVAREZE, LUCCAS; EMERICK, CAROLINA; TINCANI, ALFIO JOSE; ABU EGAL, ERIKA SAID; ALTEMANI, ALBINA; MARIANO, FERNANDA VIVANE. Spindle cell carcinoma of the lip: An immunohistochemical study of a challenging case. Oral Oncology, v. 125, p. 3-pg., 2022-02-01. (19/06809-2, 15/07304-0, 19/09419-0, 18/24715-2)

SCARINI, JOAO FIGUEIRA; DE LIMA-SOUZA, REYDSON ALCIDES; LAVAREZE, LUCCAS; EMERICK, CAROLINA; MIYAOK, RAFAELLA DINI; SCHIAVON KINASZ, LETICIA RAYSA; MAUNSELL, REBECCA; ABU EGAL, ERIKA SAID; ALTEMANI, ALBINA; MARIANO, FERNANDA VIVIANE. Oral Teratoma with Hairy Polyp-Like Features: A Brief Report of a Rare Presentation. INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY, v. N/A, p. 4-pg., 2022-11-03. (21/12567-1, 15/07304-0, 19/09419-0, 19/06809-2)

LIMA-SOUZA, REYDSON ALCIDES DE; SCARINI, JOAO FIGUEIRA; EGAL, ERIKA SAID ABU; CRESCENCIO, LIVIA RAMALHO; COSTA, JEZREEL CORRE DA; SILVA, MARIO FERNANDEZ SOBRAL; TINCANI, ALFIO JOSE; GONDAK, ROGERIO OLIVEIRA; ALTEMANI, ALBINA; MARIANO, FERNANDA VIVIANE. Secretory carcinoma ex pleomorphic adenoma of the submandibular gland: An immunohistochemical study. Oral Oncology, v. 120, SEP 2021. (19/06809-2, 15/07304-0, 19/09419-0)

GONCALVES, JUSSARA MARIA; SCARINI, JOAO FIGUEIRA; GONDAK, ROGERIO; ALTEMANI, ALBINA; MARIANO, FERNANDA VIVIANE. Oral involvement of sinonasal undifferentiated carcinoma: A case report and immunohistochemical study of a challenging case. Oral Oncology, v. 126, p. 3-pg., 2022-02-18. (15/07304-0, 19/09419-0)

KIMURA, TALITA DE CARVALHO; DE LIMA-SOUZA, REYDSON ALCIDES; SCARINI, JOAO FIGUEIRA; LAVAREZE, LUCCAS; ABU EGAL, ERIKA SAID; ALTEMANI, ALBINA; MARIANO, FERNANDA VIVIANE. Clinicopathological profile of sclerosing polycystic adenoma/adenosis: A systematic review. HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK, v. N/A, p. 9-pg., 2023-07-05. (15/07304-0, 19/09419-0, 20/08431-4)

DAMAS, INGRID IARA; LAVAREZE, LUCCAS; SCARINI, JOAO FIGUEIRA; DE LIMA-SOUZA, REYDSON ALCIDES; EMERICK, CAROLINA; GONCALVES, MAYARA TREVIZOL; FIGUEIREDO-MACIEL, TAYNA; VIEIRA, GUSTAVO DE SOUZA; KIMURA, TALITA DE CARVALHO; AQUINO, IARA GONCALVES; et al. Immunopathological insights into villitis of unknown etiology on the basis of transplant immunology. Placenta, v. 131, p. 9-pg., 2023-01-01. (19/09419-0, 20/08431-4, 15/07304-0)

ABU EGAL, ERIKA SAID; SCARINI, JOAO FIGUEIRA; DE LIMA-SOUZA, REYDSON ALCIDES; LAVAREZE, LUCCAS; FERNANDES, PATRICIA MARIA; EMERICK, CAROLINA; GONCALVES, MAYARA TREVIZOL; HELMS, MY N.; ALTEMANI, ALBINA; MARIANO, FERNANDA VIVIANE. Tumor microenvironment in salivary gland carcinomas: An orchestrated state of chaos. Oral Oncology, v. 127, p. 11-pg., 2022-02-18. (17/00831-0, 19/09419-0, 17/13167-1, 19/06809-2, 15/07304-0)

DE ANGELIS, CAMILA MATSUNAGA; DE LIMA-SOUZA, REYDSON ALCIDES; SCARINI, JOAO FIGUEIRA; ABU EGAL, ERIKA SAID; DO AMARAL-SILVA, GLEYSON KLEBER; GONDAK, ROGERIO DE OLIVEIRA; DE ALMEIDA, OSLEI PAES; CHONE, CARLOS TAKAHIRO; KOWALSKI, LUIZ PAULO; ALTEMANI, ALBINA; et al. Immunohistochemical Expression of Fatty Acid Synthase (FASN) is Correlated to Tumor Aggressiveness and Cellular Differentiation in Salivary Gland Carcinomas. Head and Neck Pathology, v. 15, n. 4, p. 8-pg., 2021-04-11. (15/07304-0, 19/09419-0)

Academic Publications

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

SCARINI, João Figueira. Genomic profile of different stages of carcinoma ex pleomorphic adenoma development: a comprehensive analysis using whole exome sequencing and array-based comparative genomic hybridization. 2024. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Faculdade de Odontologia de Piracicaba Piracicaba, SP.