Navegando por Autor "Torrezan, Giovana T."
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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 Mutation detection in tumor-derived cell free DNA anticipates progression in a patient with metastatic colorectal cancer(2018-08-10) Barros, Bruna D. de Figueiredo; Kupper, Bruna E. C.; Aguiar Junior, Samuel; Mello, Celso A. L. de; Begnam, Maria D.; Chojniak, Rubens; Souza, Sandro José de; Torrezan, Giovana T.; Carraro, Dirce M.Background: The observation of tumor-derived cell-free DNA (ctDNA) in plasma brought new expectations to monitor treatment response in cancer patients. Case presentation: In an exploratory case of a 57-year-old man diagnosed with metastatic sigmoid adenocarcinoma, we used a hotspot panel of cancer-associated gene mutations to identify tumor-specific mutations in the primary tumor and metastasis. Results: Five mutations were detected (KRAS, p.Gly12Val; TP53, p.Arg175His; RB1, p.Ile680Thr; ALK, p.Gly1184Glu; and ERBB2, p.Lys860Lys), of which three were detected in both tissue types (primary tumor and metastasis). All five mutations were monitored in the ctDNA of six serial plasma samples. Only KRAS and TP53 mutations were detected at a high frequency in the first plasma sample. After 1 month of chemotherapy the allele frequencies of both mutations fell below the detection limit. From the third month of systemic treatment onward, the allele frequencies of both mutations were detectable in plasma, displaying a continual increase thereafter. The remaining three mutations were not detected in plasma samples. Signs of disease progression in ctDNA during the treatment period were evident while computed tomography (CT) measurements suggested stable metastatic lesions throughout the treatment. Conclusions: Liquid biopsies revealed tumor heterogeneity and predicted tumor progression, demonstrating the potential of ctDNA analysis to be a sensitive and specific tool for monitoring treatment responsivity and for early identification of treatment resistance.