論文 - 詳細
| RRC ID | 38141 |
|---|---|
| 著者 | Meindl A, Hellebrand H, Wiek C, Erven V, Wappenschmidt B, Niederacher D, Freund M, Lichtner P, Hartmann L, Schaal H, Ramser J, Honisch E, Kubisch C, Wichmann HE, Kast K, Deissler H, Engel C, Müller-Myhsok B, Neveling K, Kiechle M, Mathew CG, Schindler D, Schmutzler RK, Hanenberg H. |
| タイトル | Germline mutations in breast and ovarian cancer pedigrees establish RAD51C as a human cancer susceptibility gene. |
| ジャーナル | Nat Genet |
| Abstract |
Germline mutations in a number of genes involved in the recombinational repair of DNA double-strand breaks are associated with predisposition to breast and ovarian cancer. RAD51C is essential for homologous recombination repair, and a biallelic missense mutation can cause a Fanconi anemia-like phenotype. In index cases from 1,100 German families with gynecological malignancies, we identified six monoallelic pathogenic mutations in RAD51C that confer an increased risk for breast and ovarian cancer. These include two frameshift-causing insertions, two splice-site mutations and two nonfunctional missense mutations. The mutations were found exclusively within 480 pedigrees with the occurrence of both breast and ovarian tumors (BC/OC; 1.3%) and not in 620 pedigrees with breast cancer only or in 2,912 healthy German controls. These results provide the first unambiguous evidence of highly penetrant mutations associated with human cancer in a RAD51 paralog and support the 'common disease, rare allele' hypothesis. |
| 巻・号 | 42(5) |
| ページ | 410-4 |
| 公開日 | 2010-5-1 |
| DOI | 10.1038/ng.569 |
| PII | ng.569 |
| PMID | 20400964 |
| MeSH | Alleles Breast Neoplasms / genetics* Case-Control Studies DNA-Binding Proteins / genetics Fanconi Anemia / genetics Female Genetic Predisposition to Disease* Germ-Line Mutation* Germany Humans Models, Genetic Mutation Ovarian Neoplasms / genetics* Pedigree Phenotype |
| IF | 27.605 |
| 引用数 | 451 |
| WOS 分野 | GENETICS & HEREDITY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 31 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 3.0 |
| リソース情報 | |
| ヒト・動物細胞 | ΔRad51B-DT40(RCB1622) |