| Grant number: | 15/20748-5 |
| Support Opportunities: | Regular Research Grants |
| Start date: | March 01, 2016 |
| End date: | July 31, 2018 |
| Field of knowledge: | Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology |
| Principal Investigator: | Silvia Regina Rogatto |
| Grantee: | Silvia Regina Rogatto |
| Host Institution: | Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil |
| Associated researchers: | Fabio Albuquerque Marchi ; Luiz Paulo Kowalski |
Abstract
Thyroid nodules are common in adult population, being detected in up to 70% of cases by ultrasound tests. However, current diagnostic methods have limitations in distinguishing malignant from benign follicular lesions, resulting in a significant number of potentially preventable surgeries. Thus, molecular diagnostic and prognostic tools useful in the clinical practice for thyroid lesions are of great interest. In two previous studies of our group, potential markers were identified based on the comprehensive analysis of gene expression and DNA methylation in malignant and benign thyroid lesions. Based on these preliminary results obtained in surgical specimens, the goal of this study is to prospectively test the potential of these putative diagnostic markers in thyroid lesions obtained directly from fine needle aspiration biopsies (FNAB). Due to the high frequency of BRAF mutations in cases of papillary thyroid carcinoma (PTC), the evaluation of this alteration will be incorporated to improve the performance of the test based on DNA analysis. In a second prior study of our group, DNA methylation profile of PTC paired with adjacent normal tissue samples revealed the involvement of differentially methylated miRNA-encoding genes. PTC is the most common thyroid malignancy, and despite the generally indolent tumor behavior, some of the patients have aggressive disease with no effective therapeutic options. Thus, we intend to perform a functional study addressing the impact of methylation and expression of these miRNAs in thyroid cancer cell lines. This project was designed with two main objectives: (1) to confirm the applicability and performance of the molecular assays using biopsies obtained at AC Camargo Cancer Center and (2) to characterize the epigenetic changes involved in the regulation of the miRNAs expression and to perform functional assays, which may allow advancing knowledge of PTC carcinogenesis with potential to reveal new therapeutic targets. (AU)
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