Abstract
The prevalence of thyroid nodules depends on several factors such as age, population studied, sex and method of evaluation. Due to the use of high-resolution ultrasound, which can detect nodules as small as 2 mm, the prevalence of thyroid nodules has increased, reaching up to 67 %. As a consequence of the increase in the diagnosis of the nodules, we also observed an increased incidence of thyroid cancer. Currently, thyroid cancer is the fastest growing cancer incidence worldwide. According to the National Cancer Institute (INCA), thyroid neoplasms represent 5.6% of cancers in women, currently being the fourth most common type of cancer in the female Brazilian adult population. It is suggested that this trend is directly related to the increased frequency of papillary thyroid carcinoma and its variants. In fact, approximately 50 % of the increase was at the expense of the diagnosis of micropapillary carcinomas (tumors d 1 cm). Similar to adults, the incidence rate of pediatric thyroid cancer has also increased, being the papillary histological type the most prevalent subtype. This project will address clinical problems related to diagnosis and prognosis of thyroid nodules. Primarily, we sought to identify new genetic events associated with the genesis of different thyroid carcinoma subtypes that can be used as preoperative diagnostic markers that can help the distinction of nodules commonly classified as indeterminate that occur both in the adult or pediatric ages. We believe that the identification of these new markers will enable us to develop a diagnostic test, which may have increased sensitivity and specificity of the tests currently available. Also aims to identify markers capable of predicting the prognosis of thyroid nodules, particularly micropapillary carcinomas. It also seeks to contribute to the determination of genetic events associated with the genesis and progression of medullary thyroid carcinoma occurring in sporadic and hereditary forms. As a strategy to identify new recurrent somatic mutations and/or gene fusion events, we will use whole exome sequencing and/or RNA (paired-end RNA sequencing) or Target Ressenquencing, since 85% of the disease-causing mutations are located in coding regions of the genome. These strategies have achieved high levels of success in identifying genes associated with diseases, especially in cancer. In addition to identifying new genetic events, this project also aims to characterize the signaling pathway associated with new genes and new mutations previously identified in thyroid cancer by our group. This is an innovative proposal whose results may have immediate clinical application, as well as may contribute in the identification of new signaling pathways involved in the genesis and progression of tumors of the thyroid and thus open new perspectives for targeted therapy. (AU)
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