Cancer predisposing BARD1 mutations affect exon skipping and are associated with overexpression of specific BARD1 isoforms.
Oncol Rep
; 34(5): 2609-17, 2015 Nov.
Article
en En
| MEDLINE
| ID: mdl-26329992
ABSTRACT
BARD1 is the main binding partner of BRCA1 and is required for its stability and tumor-suppressor functions. In breast cancer and other epithelial cell carcinomas, alternatively spliced isoforms of BARD1 are highly upregulated and correlated with poor outcome. Recent data indicate that germline mutations of BARD1 may predispose to breast and/or ovarian cancer. To evaluate the role of BARD1 germline mutations in predisposition to ovarian cancer we scanned a cohort of 255 patients for the presence of previously reported mutations located in exons 5, 8 and 10 using high-resolution melting analysis. Within this group we identified single-patients carrying mutation in exon 8 (c.1690C>T, p.Gln564Ter), two different variants in exon 10 (c.1972C>T, p.Arg658Tyr; c.1977A>G, p.=) and a carrier of novel missense mutation located in exon 5 (c.1361C>T, p.Pro454Leu). Three out of four identified mutations alter exonic splicing enhancing motives and result in expression of incorrect splicing skipping of exons 5, 8, and 2-9, respectively. Our data indicate that BARD1 variants may predispose to ovarian cancer in limited number of patients although based on actual data it is difficult to estimate its actual penetrance.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Ováricas
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Empalme Alternativo
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Mutación de Línea Germinal
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Mutación Missense
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Proteínas Supresoras de Tumor
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Ubiquitina-Proteína Ligasas
Tipo de estudio:
Risk_factors_studies
Límite:
Adult
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Aged
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Aged80
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Female
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Humans
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Middle aged
Idioma:
En
Revista:
Oncol Rep
Asunto de la revista:
NEOPLASIAS
Año:
2015
Tipo del documento:
Article
País de afiliación:
Polonia