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Identification of a novel in-frame deletion in BRCA2 and analysis of variants of BRCA1/2 in Italian patients affected with hereditary breast and ovarian cancer

icecream 添加于 2012-12-2 21:36 | 1338 次阅读 | 0 个评论

作者
Vietri MT, Molinari AM, De Paola ML, Cantile F, Fasano M, Cioffi M
摘要
Abstract Background: An estimated 5%-10% of all breast cancers are due to an inherited predisposition and, out of these, about 30% are caused by germline mutations of the BRCA1 and BRCA2 genes. The prevalence of germline mutations in the BRCA1and BRCA2 genes varies among ethnic groups. The aims of this study are to evaluate deleterious mutations and genomic rearrangements in BRCA1/2 genes and the CHEK2 1100delC mutation in a cohort of Italian women affected with hereditary breast and/or ovarian cancer. In addition we clarify the effect of the novel variants identified in BRCA2 gene by mRNA analysis and prediction software. Methods: We enrolled 103 consecutive Italian patients affected with hereditary breast and/or ovarian cancer, aged 23-69 years. Results: We found BRCA1/2 mutations in 15/103 probands (14.6%). Among these, a BRCA2 gene mutation has not been described previously. In addition, we identified five novel BRCA2 variants (S1341, IVS1-59t>c, IVS11-74insA, IVS12+74c>g and I1167V). No genomic BRCA1/2 rearrangements or CHEK2 1100delC mutation was found in our patients. The novel BRCA2 mutation NS1742del (p.N1742_S1743del) was an in-frame 6 bp deletion that results in loss of two amino acids. Conclusions: In silico analysis conducted for S1341, IVS1-59t>c, IVS11-74insA and IVS12+74c>g of BRCA2 predicted the variants as neutral and benign, whereas the results for I1167V was inconclusive. mRNA analysis for the novel BRCA2 intronic variant IVS11-74insA and the already published BRCA1 variant C197 shows that they have no effect on the splicing. These results are in agreement with in silico analysis.
详细资料
- 文献种类: Journal Article
- 期刊名称: Clinical Chemistry and Laboratory Medicine : CCLM / FESCC
- 期刊缩写: Clin Chem Lab Med
- 期卷页: 2012年
- ISBN: 1434-6621
学科领域生物医药 » 预防卫生学
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