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)
Articles published in Agência FAPESP Newsletter about the research grant:
MARIANO, FERNANDA VIVIANE;
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;
Somatic copy number alterations in pleomorphic adenoma and recurrent pleomorphic adenoma.
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY,
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