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Study of genetic and metabolic changes of pleomorphic adenoma and carcinoma ex pleomorphic adenoma by exome, gene expression and immunohistochemistry

Grant number: 15/07304-0
Support type:Research Grants - Young Investigators Grants
Duration: February 01, 2017 - April 30, 2022
Field of knowledge:Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
Principal researcher:Fernanda Viviane Mariano Brum Corrêa
Grantee:Fernanda Viviane Mariano Brum Corrêa
Home Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Assoc. researchers:Albina Messias de Almeida Milani Altemani ; Luciana Souto Mofatto ; Luiz Lehmann Coutinho ; Luiz Paulo Kowalski ; Marcelo Falsarella Carazzolle ; Oslei Paes de Almeida ; Ricardo Della Coletta
Associated scholarship(s):20/08431-4 - METABOLOMIC PROFILING ANALYSIS IN THE MALIGNANT TRANSFORMATION OF PLEOMORPHIC ADENOMA, BP.DR
19/09419-0 - Genomic alterations in the malignant transformation of the Pleomorphic Adenoma, BP.DR
20/04127-9 - Study of genetic and metabolic changes of pleomorphic adenoma and carcinoma ex pleomorphic adenoma by exome, gene expression and immunohistochemistry, BP.TT
+ associated scholarships 19/10788-0 - Morphological and metabolic comparative study between carcinoma ex pleomorphic adenoma of lacrimal and salivar glands, BP.IC
19/06809-2 - Analysis of mass spectrometry in the malignant transformation of the pleomorphic adenoma. correlation of data with gene expression and exome, BP.MS
18/25294-0 - Study of genetic and metabolic changes of pleomorphic adenoma and carcinoma ex pleomorphic adenoma by exome, gene expression and immunohistochemistry, BP.TT
17/13167-1 - Study of metabolic changes of pleomorphic adenoma and carcinoma ex pleomorphic adenoma by immuno-histochemistry, BP.IC
17/00831-0 - Study of genetic and metabolic changes of pleomorphic adenoma and carcinoma ex pleomorphic adenoma by exome, gene expression and immunohistochemistry, BP.JP - associated scholarships

Abstract

The pleomorphic adenoma (PA) is the most common tumor of the salivary gland and although benign, it has chances of recurrence and malignant transformation to carcinoma ex pleomorphic adenoma (CXPA). The latter is an aggressive neoplasm occurring with metastasis and death in a large percentage of cases. Although both tumors have important discoveries in genetic and molecular areas, the changes found are focal and in specific genetic sites. There are still many questions about the diagnostic market, pathogenesis and target therapy of PA and CXPA. In this project, we will study a group of PAs and CXPAs (subdivided according to histological type and degree of progression) through the complete sequencing of the exome (Whole Exome Sequencing - WES) and added the findings to prior results from our group by array-CGH technique.We will do validation of these reactions (exome and array-CGH) by Sanger sequencing and after we will analyse the candidate genes through gene expression. Thus, with our work, we will extend the individual genetic knowledge on PAs and CXPAs, and we will still be able to compare the copy number alterations and mutations acquired in benign counterpart and that are conserved in carcinoma, as well as new unique events of the malignant tumor, trying to do correlaction with progression and histopathological subtype. Since the pathogenesis of cancer is characterized by a complex mix of genetic and metabolic changes, we will also study various metabolic pathways (glucogenesis, lipogenesis) through immunohistochemical markers, gene expression and we will investigate the exome and array-CGH findings searching relation with these pathways. With this broad approach, analyzing genetic and metabolic changes involved in tumorigenesis PA, CXPA carcinogenesis and tumor progression, we intend to add significant knowledge to what is known today expecting to discovery markers for diagnosis, pathogenesis and target therapy. (AU)

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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)
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. Web of Science Citations: 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; MARIANO, FERNANDA VIVIANE. 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. Web of Science Citations: 0.
SCARINI, JOAO FIGUEIRA; ABU EGAL, ERIKA SAID; DE LIMA-SOUZA, REYDSON ALCIDES; CRESCENCIO, LIVIA RAMALHO; EMERICK, CAROLINA; KOWALSKI, LUIZ PAULO; ALTEMANI, ALBINA; MARIANO, FERNANDA VIVIANE. Two sides of the same coin: Insights into the myoepithelial cells in carcinoma ex pleomorphic adenoma development. CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY, v. 157, JAN 2021. Web of Science Citations: 0.
SCARINI, JOAO FIGUEIRA; ROSA, LARISSA FERNANDES; DE LIMA SOUZA, REYDSON ALCIDES; ABU EGAL, ERIKA SAID; TINCANI, ALFIO JOSE; MARTINS, ANTONIO SANTOS; KOWALSKI, LUIZ PAULO; GRANER, EDGARD; DELLA COLETTA, RICARDO; CARLOS, ROMAN; GONDAK, ROGERIO DE OLIVEIRA; DE ALMEIDA, OSLEI PAES; DE ALMEIDA MILANI ALTEMANI, ALBINA MESSIAS; BASTOS, DEBORA CAMPANELLA; MARIANO, FERNANDA VIVIANE. Gene and immunohistochemical expression of HIF-1 alpha, GLUT-1, FASN, and adipophilin in carcinoma ex pleomorphic adenoma development. ORAL DISEASES, v. 26, n. 6 APR 2020. Web of Science Citations: 0.
DOS SANTOS, ERISON S.; RAMOS, JOAB C.; NORMANDO, ANA GABRIELA C.; MARIANO, V, FERNANDA; PAES LEME, ADRIANA F. Epigenetic alterations in salivary gland tumors. ORAL DISEASES, JAN 2020. Web of Science Citations: 0.
MARIANO, FERNANDA VIVIANE; FIDALGO, FELIPE; MAION CASARIM, ANDRE LUIS; MARTINS, ANTONIO SANTOS; SCARINI, JOAO FIGUEIRA; DE LIMA SOUZA, REYDSON ALCIDES; EGAL, ERIKA SAID; KOWALSKI, LUIZ PAULO; VICTORINO KREPISCHI, ANA CRISTINA; ALTEMANI, ALBINA. Somatic copy number alterations in pleomorphic adenoma and recurrent pleomorphic adenoma. ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY, v. 129, n. 1, p. 59-64, JAN 2020. Web of Science Citations: 0.
SOARES, CIRO DANTAS; DE LIMA MORAIS, THAYNA MELO; CARLOS, ROMAN; MARTINS, MANOELA DOMINGUES; DE ALMEIDA, OSLEI PAES; MARIANO, FERNANDA VIVIANE; ALTEMANI, ALBINA. Immunohistochemical expression of mammaglobin in salivary duct carcinomas de novo and salivary duct carcinoma ex pleomorphic adenoma. HUMAN PATHOLOGY, v. 92, p. 59-66, OCT 2019. Web of Science Citations: 0.
PULIDO DIAZ, KATYA; GONDAK, ROGERIO; MARTINS, LEANDRO LIPORONI; DE ALMEIDA, OSLEI PAES; LEON, JORGE ESQUICHE; MARIANO, FERNANDA VIVIANE; ALTEMANI, ALBINA; VARGAS, PABLO AGUSTIN. Fatty acid synthase and Ki-67 immunoexpression can be useful for the identification of malignant component in carcinoma ex-pleomorphic adenoma. JOURNAL OF ORAL PATHOLOGY & MEDICINE, v. 48, n. 3, p. 232-238, MAR 2019. Web of Science Citations: 2.

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