Predisposition gene identification in thyroid and breast carcinomas syndrome by exoma sequencing

Abstract

Hereditary cancer syndromes are estimated to account for 10% of all tumors, while 15% of cases are associated with familial aggregation of cancer. The etiology of solid tumors, including breast carcinomas (BC) and thyroid carcinomas (TC), is multifactorial, dependent on environmental and genetic factors playing a variable role in the disease etiology. However, a significant incidence of these tumors is associated with a hereditary component. Thus, the identification of predisposition factors and characterization of the genetic risk are essential for diagnosis, prognosis and genetic counseling of affected members of these families. Within this context, the Exome Sequence Technology, based on genome protein coding sequence capture by hybridization, has been applied for searching the disease-related variations, mainly in monogenic inherited disorders. About 85% of the large effects mutations happen at protein coding sequence, found in both exonic regions and splicing sites. In this study, which aims to identify predisposition genes associated with breast and thyroid carcinomas, it will be evaluated the exoma of 30 families with history of breast and thyroid cancer selected by well-defined criteria. The selected probands are negative for common mutations in major hereditary predisposition genes-related with these tumors, including BRCA1, BRCA2, TP53 e CHEK2. The detection and definition of novel genetic alterations associated with these tumors could extend the spectrum of hereditary cancer syndromes, permit the identification of patients at risk of developing these tumors, as well as contribute with the molecular diagnoses and genetic counseling of those families.