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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Germline mutations in BRCA1 and BRCA2 in epithelial ovarian cancer patients in Brazil

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Maistro, Simone ; Teixeira, Natalia ; Encinas, Giselly ; Hirata Katayama, Maria Lucia ; Tavares Niewiadonski, Vivian Dionisio ; Cabral, Larissa Garcia ; Ribeiro, Roberto Marques ; Gaburo Junior, Nelson ; Ribeiro Chaves de Gouvea, Ana Carolina ; Carraro, Dirce Maria ; Sabino, Ester Cerdeira ; Estevez Diz, Maria del Pilar ; Chammas, Roger ; de Bock, Geertruida Hendrika ; Azevedo Koike Folgueira, Maria Aparecida
Total Authors: 15
Document type: Journal article
Source: BMC CANCER; v. 16, DEC 3 2016.
Web of Science Citations: 14
Abstract

Background: Approximately 8-15% epithelial ovarian cancer patients are BRCA1 or BRCA2 germline mutation carriers. Brazilian inhabitants may have peculiar genetic characteristics associated with ethnic diversity, and studies focusing on the entire BRCA1/BRCA2 gene sequencing in Brazilian ovarian cancer patients are still lacking. The aim of this study was to evaluate BRCA1/2 mutations, through entire gene sequencing, in a Brazilian population of women with epithelial ovarian cancer. Methods: In a cross sectional study performed in one reference centre for cancer treatment in Sao Paulo, Brazil, 100 patients diagnosed with epithelial ovarian cancer unselected for family history of breast and/or ovarian cancer were included. The complete coding sequence of BRCA1/2 genes was evaluated through Next-Generation or capillary sequencing. Large deletions were investigated through Multiplex Ligation-dependent Probe Amplification (MLPA). Results: Nineteen pathogenic mutations (BRCA1: n = 17 and BRCA2: n = 2) featuring 14 different mutations, including two large deletions in BRCA1 (exon 1-2 deleted and exon 5-7 deleted) were identified. Three mutations were detected more than once (c.3331\_3334delCAAG, c.5266dupC and c.4484G > T). Two novel frameshift mutations were identified, one in BRCA1 (c.961\_962delTG) and one in BRCA2 (c.1963\_1963delC). BRCA1/2 mutations were seen in 35.5% of the patients with first and/or second-degree relatives with breast and/or ovarian cancer. Nineteen variants of uncertain significance (VUS) were detected (BRCA1: n = 2 and BRCA2: n = 17), including five distinct missense variants (BRCA1: c. 5348 T > C; BRCA2: c.2350A > G, c.3515C > T, c.7534C > T, and c.8351G > A). Conclusions: Among epithelial ovarian cancer patients unselected for family history of cancer, 19% were BRCA1/2 germline mutation carriers. Almost 3/4 of the BRCA mutations, including two large deletions, were detected only once. Our work emphasizes the need of entire gene sequencing and MLPA screening in Brazil. (AU)

FAPESP's process: 11/09572-1 - Somatic and Germline Mutations in Young Patients with Breast Cancer
Grantee:Giselly Encinas Zanetti
Support type: Scholarships in Brazil - Doctorate