Cancer predisposing missense and protein truncating BARD1 mutations in non‐BRCA1 or BRCA2 breast cancer families |
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| Authors: | Sylvia De Brakeleer Jacques De Grève Remy Loris Nicolas Janin Willy Lissens Erica Sermijn Erik Teugels |
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| Affiliation: | 1. Laboratory of Molecular Oncology, Vrije Universiteit Brussel, 1090 Brussels, Belgium;2. Familial Cancer Clinic, UZ Brussel, 1090 Brussels, Belgium;3. Structural Biology Brussels, Vrije Universiteit Brussel, 1050 Brussels, Belgium;4. Department of Molecular and Cellular Interactions, VIB, 1050 Brussels, Belgium;5. Department of Human Genetics, CHU de Liège, 4000 Liège, Belgium;6. Centre for Medical Genetics (EMGE), UZ Brussel, 1090 Brussels, Belgium |
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| Abstract: | Fifteen years ago BRCA1 and BRCA2 were reported as high penetrant breast cancer predisposing genes. However, mutations in these genes are found in only a fraction of high risk families. BARD1 is a candidate breast cancer gene, but only a limited number of missense mutations with rather unclear pathogenic consequences have been reported.We screened 196 high risk breast cancer families for the occurrence of BARD1 variants. All genetic variants were analyzed using clinical information as well as IN SILICO predictive tools, including protein modeling. We found three candidate pathogenic mutations in seven families including a first case of a protein truncating mutation (p.Glu652fs) removing the entire second BRCT domain of BARD1. In conclusion, we provide evidence for an increased breast cancer risk associated to specific BARD1 germline mutations. However, these BARD1 mutations occur in a minority of hereditary breast cancer families. ©2010 Wiley‐Liss, Inc. |
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| Keywords: | Breast cancer hereditary BARD1 predisposing mutation |
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