Department of Clinical Genetics and Biocenter Oulu, University of Oulu, Oulu University Hospital, Oulu, Finland.
BMC Med Genet. 2011 Jul 21;12:98. doi: 10.1186/1471-2350-12-98.
Currently known susceptibility genes such as BRCA1 and BRCA2 explain less than 25% of familial aggregation of breast cancer, which suggests the involvement of additional susceptibility genes. RNF8, UBC13 and MMS2 are involved in the DNA damage response pathway and play important roles in BRCA1-mediated DNA damage recognition. Based on the evidence that several players in the ubiquitin-mediated BRCA1-dependent DDR seem to contribute to breast cancer predisposition, RNF8, UBC13 and MMS2 were considered plausible candidate genes for susceptibility to breast cancer.
The entire coding region and splice junctions of RNF8, UBC13 and MMS2 genes were screened for mutations in affected index cases from 123 Northern Finnish breast cancer families by using conformation sensitive gel electrophoresis, high resolution melting (HRM) analysis and direct sequencing.
Mutation analysis revealed several changes in RNF8 and UBC13, whereas no aberrations were observed in MMS2. None of the found sequence changes appeared to associate with breast cancer susceptibility.
The present data suggest that mutations in RNF8, UBC13 and MMS2 genes unlikely make any sizeable contribution to breast cancer predisposition in Northern Finland.
目前已知的易感基因，如 BRCA1 和 BRCA2，只能解释不到 25%的乳腺癌家族聚集现象，这表明还存在其他易感基因。RNF8、UBC13 和 MMS2 参与 DNA 损伤反应途径，在 BRCA1 介导的 DNA 损伤识别中发挥重要作用。鉴于泛素介导的 BRCA1 依赖性 DDR 中的几个参与者似乎有助于乳腺癌易感性，因此 RNF8、UBC13 和 MMS2 被认为是乳腺癌易感的候选基因。
通过构象敏感凝胶电泳、高分辨率融解（HRM）分析和直接测序，对 123 个来自芬兰北部的乳腺癌家族的受影响的指数病例中的 RNF8、UBC13 和 MMS2 基因的整个编码区和剪接接头进行突变筛选。
突变分析显示 RNF8 和 UBC13 中存在几种变化，而 MMS2 中未观察到异常。发现的序列变化均与乳腺癌易感性无关。
本研究数据表明，RNF8、UBC13 和 MMS2 基因的突变不太可能对芬兰北部的乳腺癌易感性有任何显著贡献。
