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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.
Background
Among
the gynaecological malignancies, ovarian cancer has the highest
mortality rate in developed countries and is the second leading cause of
mortality in developing countries. In Brazil, 6150 new cases of ovarian
cancer are expected in 2016, and in 2013, ovarian cancer accounted for
3283 deaths, indicating its importance in public health [1].....
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