Navegando por Autor "Souza, Jorge E. S. de"
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Artigo Complex landscape of germline variants in brazilian patients with hereditary and early onset breast cancer(2018-05-07) Torrezan, Giovana T.; Almeida, Fernanda G. dos Santos R. de; Figueiredo, Márcia C. P.; Barros, Bruna D. de Figueiredo; Paula, Cláudia A. A. de; Valieris, Renan; Souza, Jorge E. S. de; Ramalho, Rodrigo F.; Silva, Felipe C. C. da; Ferreira, Elisa N.; Nóbrega, Amanda F. de; Felicio, Paula S.; Achatz, Maria I.; Souza, Sandro José de; Palmero, Edenir I.; Carraro, Dirce M.Pathogenic variants in known breast cancer (BC) predisposing genes explain only about 30% of Hereditary Breast Cancer (HBC) cases, whereas the underlying genetic factors for most families remain unknown. Here, we used whole-exome sequencing (WES) to identify genetic variants associated to HBC in 17 patients of Brazil with familial BC and negative for causal variants in major BC risk genes (BRCA1/2, TP53, and CHEK2 c.1100delC). First, we searched for rare variants in 27 known HBC genes and identified two patients harboring truncating pathogenic variants in ATM and BARD1. For the remaining 15 negative patients, we found a substantial vast number of rare genetic variants. Thus, for selecting the most promising variants we used functional-based variant prioritization, followed by NGS validation, analysis in a control group, cosegregation analysis in one family and comparison with previous WES studies, shrinking our list to 23 novel BC candidate genes, which were evaluated in an independent cohort of 42 high-risk BC patients. Rare and possibly damaging variants were identified in 12 candidate genes in this cohort, including variants in DNA repair genes (ERCC1 and SXL4) and other cancer-related genes (NOTCH2, ERBB2, MST1R, and RAF1). Overall, this is the first WES study applied for identifying novel genes associated to HBC in Brazilian patients, in which we provide a set of putative BC predisposing genes. We also underpin the value of using WES for assessing the complex landscape of HBC susceptibility, especially in less characterized populations.Artigo S-Score: A Scoring System for the Identification and Prioritization of Predicted Cancer Genes(2014-04-07) Souza, Jorge E. S. de; Fonseca, André F.; Valieris, Renan; Carraro, Dirce M.; Wang, Jean Y. J.; Kolodner, Richard D.; Souza, Sandro José deA new method, which allows for the identification and prioritization of predicted cancer genes for future analysis, is presented. This method generates a gene-specific score called the "S-Score" by incorporating data from different types of analysis including mutation screening, methylation status, copy-number variation and expression profiling. The method was applied to the data from The Cancer Genome Atlas and allowed the identification of known and potentially new oncogenes and tumor suppressors associated with different clinical features including shortest term of survival in ovarian cancer patients and hormonal subtypes in breast cancer patients. Furthermore, for the first time a genome-wide search for genes that behave as oncogenes and tumor suppressors in different tumor types was performed. We envisage that the S-score can be used as a standard method for the identification and prioritization of cancer genes for follow-up studies.