Germline mutations in BRCA1 and BRCA2 in epithelial ovarian cancer patients in Brazil.
BMC Cancer
; 16(1): 934, 2016 12 03.
Article
en En
| MEDLINE
| ID: mdl-27914478
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.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Ováricas
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Mutación de Línea Germinal
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Neoplasias Glandulares y Epiteliales
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Proteína BRCA1
/
Proteína BRCA2
Tipo de estudio:
Observational_studies
/
Prevalence_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Adult
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Aged
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Aged80
/
Female
/
Humans
/
Middle aged
País/Región como asunto:
America do sul
/
Brasil
Idioma:
En
Revista:
BMC Cancer
Asunto de la revista:
NEOPLASIAS
Año:
2016
Tipo del documento:
Article
País de afiliación:
Brasil