Identification of predisposition genes to the development of familial non-medullary thyroid cancer by exome data analysis

Abstract

Thyroid cancer is the most common endocrine neoplasia, its incidence has been increasing in the last decades. Data from INCA suggest that for each year from 2020-2022 triennium there will be 1.830 cases in men and 11.950 in women. The benign nodules originated from follicular cells are called follicular adenomas; the malignant nodules generated from parafollicular cells will give rise to Medullary Thyroid Carcinomas (MTC); those originated from follicular cells, will give rise to Undifferentiated or Anaplastic Thyroid Carcinomas (ATC), Poorly Differentiated Thyroid Carcinomas (PDTC) and Well Differentiated Thyroid Carcinomas (DTC). In thyroid cancer critic genes are altered by two main mechanisms, point mutations and chromosomal rearrangements. Genes commonly involved in thyroid tumorigenesis include BRAF, RAS, RET, PTEN e PPARG; involved in MAPK and PI3K/AKT pathways that are associated with cellular processes and are highly regulated. Cancer genetics alterations can have different origins, when they are acquired during life, the cancer is called sporadic; when they are inherited and are present in germline, the cancer is called hereditary; and the familial cancer, occurs with more frequently in a family than the expected in the population, with early manifestation and presence of mutation related to increased susceptibility to cancer. Familial cancers can be classified into medullary (MTC), of which many cases are part of Multiple Endocrine Neoplasia type 2; and into non-medullary (FNMTC). FNMTC have been described in syndromic form, with a few known driver germline mutations; and in the non-syndromic, which little is known about its genetic susceptibility, which has already been shown to be related with alterations in genes and also in chromosomal loci. The present project goal is to screen mutations (already described or not) in genes that have been related as causing or risk factors in families that have non-syndromic FNMTC.