Estudo genômico para identificação de loci de risco para carcinoma familial não medular da tireoide

Abstract

The incidence of thyroid differentiated carcinomas in Rio Grande do Norte, Brazil, is relatively high. Incidentally, we observed a prominent occurrence of cases of papillary carcinomas in members of the same families identified in our series, based on routine clinical observations. In some families we have detected three or more cases of papillary carcinoma diagnosed among first and second degree, kinship patients. Thus, we decided to deepen the study regarding the etiopathogenesis of these tumors in order to establish if there is any coincident expression among these people, which may justify such prevalence and draw a clinical and genetic profile from the analysis of exome sequencing through from the study of DNA extracted from blood samples collected from these patients and their families. We found that exome sequencing performed in family IV, with non-medullary thyroid cancer, in four patients with papillary thyroid carcinoma in three consecutive generations, identified a mutation in the gene X, when adenine was replaced by cytosine (A> C) in exon X. And this nucleotide change caused the shift from isoleucine to methionine at position X (p.xM). This variant was classified as deleterious and probably harmful. This gene X is an important component of the basement membrane and scientific evidence has shown that it has a function related to migration, invasion and tumor progression. With the information provided by the new generation genetic sequencing, pointing out genes associated with differentiated thyroid carcinoma, it will be possible to improve the diagnosis, treatment management and screening of family members affected by thyroid nodular disease, impacting the various indexes of measurement of the results health promotion. This project is original as it addresses a research topic not yet clarified in the literature and unpublished in our country.