Artículos de revistas
Germline mutations in BRCA1 and BRCA2 in epithelial ovarian cancer patients in Brazil
Fecha
2016Registro en:
BMC Cancer. 2016 Dec 03;16(1):934
10.1186/s12885-016-2966-x
Autor
Maistro, Simone
Teixeira, Natália
Encinas, Giselly
Katayama, Maria Lucia Hirata
Niewiadonski, Vivian Dionisio Tavares
Cabral, Larissa Garcia
Ribeiro, Roberto Marques
Gaburo Junior, Nelson
Gouvêa, Ana Carolina Ribeiro Chaves de
Carraro, Dirce Maria
Sabino, Ester Cerdeira
Diz, Maria del Pilar Estevez
Chammas, Roger
Bock, Geertruida Hendrika de
Folgueira, Maria Aparecida Azevedo Koike
Institución
Resumen
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 São 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 ¾ 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.