Molecular Characterization of thyroid tumors using whole exome sequencing: Search for diagnostic molecular markers

Abstract

For establishing whether thyroid lesions are benign or malignant, fine-needle aspiration cytology (FNAC) is currently the gold standard. However, about 30% of all FNA samples are diagnosed as indeterminate for malignancy and often prompting diagnostic hemithyroidectomy. From those, 15-30% are in fact malignant, and most of them prove to be follicular thyroid cancer (FTC) and follicular variant of papillary thyroid cancer (FVPTC). Although discovery of specific genetic lesions in different histotypes of thyroid cancer has brought the possibility of improving the diagnostic accuracy of FNAC as molecular markers combined to cytology, some of those histotypes are still poorly understood and can represent a challenge. Hence, using whole exome sequencing (WES) the aim of this study is first identifying specific genetic alterations associated with FTC and FVPTC. Confirm frequency and specificity validating our findings in a bigger panel of samples with all different thyroid lesions (benign and malignant). Further, we intent to test a panel of described mutations in association with genetic alterations found in the WES in a new set of tumor and the corresponded FNA. Finally, we will verify pathways that may be involved with these new specific genetic alterations. If we succeed, we will be able to identify new genes involved with FTC and FVPTC pathogenesis and/or progression, and help to develop a molecular testing that in combination with cytology can improve the diagnosis accuracy allowing better prediction of malignancy in nodules with indeterminate cytology and therefore, decrease treatment cost and morbidity.