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

• 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 Opportunities: Scholarships in Brazil - Doctorate