|Support type:||Scholarships in Brazil - Doctorate|
|Effective date (Start):||February 01, 2014|
|Effective date (End):||January 31, 2018|
|Field of knowledge:||Biological Sciences - Genetics - Human and Medical Genetics|
|Principal Investigator:||Ileana Gabriela Sánchez de Rubió|
|Grantee:||Erika Urbano de Lima|
|Home Institution:||Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil|
Approximately 95% of cancers of the thyroid correspond variants originating from follicular cells (NMTC), which are subdivided into: papillary (80-85%), follicular (7-15%), Hurtle cells (2-4%) and anaplastic (1-2%), with cases mostly sporadic. Already the familiar forms of non-syndromic NMTC (FNMTC) are rare, occurring in only 5-15%. The FNMTC is characterized by the existence of three or more first-degree relatives affected by thyroid cancer. In this way, the tumors occur early and are mostly more aggressive and high rates of extension extrathyroid and metastases in the lymph nodes (40-50% of cases). Patients with FNMTC higher risk for developing breast cancer, kidney, colon, bladder, as well as melanomas and lymphomas. According to reports in the literature, it is believed that the FNMTC may be an autosomal dominant disease with variable penetrance. So far some chromosomal loci were associated with FNMTC (1q21, 2q21, 6q22, 8p23.1-p22 and 19p13.2, telomere-telomerase complex, FOXE1), possibly linked to some rare variants of this disease (oxyphil cells or follicular variant/renal papillary neoplasm). However the molecular profile FNMTC remains unknown. Until now, the molecular diagnosis of hereditary cancer was mainly based on Sanger sequencing and highly sensitive techniques such as MLPA, but that only detect known changes or in linkage analysis using microsatellites. However, the new NGS platforms have a more cost effective since they allow you to trace the complete genome, generating information on millions of base pairs in a single run, in a short time. In recent years these new tools NGS has been widely used in the characterization of rare diseases or hereditary in the vast majority show no changes or specific regions associated with the disease. In addition, these new platforms feature high efficiency for detection of different types of changes in genomic DNA as single nucleotide substitutions (SNPs), small or large insertions and deletions, copy number variations (CNVs) and chromosomal rearrangements. Due to the variability of the clinical features observed in several families affected by NMTC reported in the literature and no candidate genes associated to FNMTC clearly the objective of this study is to identify genetic changes involved in FNMTC a Brazilian family coming from Manaus (Amazonas, Brazil) that has 9 members with multinodular goiter, three of whom developed papillary carcinoma of the thyroid. This will performed whole-genome sequencing (WGS) DNA samples from peripheral leukocytes of 6 patients of this family (three goiter and CNMFT and three with goiter) using equipment SOLID® 5 (Life Technologies, Foster City, CA). Specific programs will be employed for analysis and the information of normal individuals available databases to identify genomic changes that may be associated with the disease. After the selection of candidates changes, there will be tracking these in other family members and in normal subjects to determine which segregate with the disease. This study will contribute to understanding the molecular basis involved in cancer and familial medullary not allow the identification of families at risk of developing cancer, aiding in the genetic counseling of this family and others.