VBCRC Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
Hum Mutat. 2012 Jan;33(1):95-9. doi: 10.1002/humu.21625. Epub 2011 Nov 4.
There is strong evidence that overtly inactivating mutations in RAD51C predispose to hereditary breast and ovarian cancer but the prevalence of such mutations, and whether they are associated with a particular clinical phenotype, remains unclear. Resolving these questions has important implications for the implementation of RAD51C into routine clinical genetic testing. Consequently, we have performed a large RAD51C mutation screen of hereditary breast and ovarian cancer families, and the first study of unselected patients diagnosed with ovarian cancer. Our data confirm a consistent but low frequency (2/335 families) of inactivating RAD51C mutations among families with a history of both breast and ovarian cancer and an absence of mutations among breast cancer only families (0/1,053 families). Our data also provide support for the designation of the missense variant p.Gly264Ser as a moderate penetrance allele.
有强有力的证据表明，RAD51C 显性失活突变可导致遗传性乳腺癌和卵巢癌，但此类突变的普遍性及其是否与特定的临床表型相关尚不清楚。解决这些问题对于将 RAD51C 纳入常规临床遗传检测具有重要意义。因此，我们对遗传性乳腺癌和卵巢癌家族进行了大规模 RAD51C 突变筛查，并首次对未经选择的卵巢癌患者进行了研究。我们的数据证实，在既有乳腺癌又有卵巢癌病史的家族中，失活 RAD51C 突变的频率一致但较低（2/335 个家族），而仅患有乳腺癌的家族中不存在突变（0/1053 个家族）。我们的数据还为将错义变异 p.Gly264Ser 指定为中度外显率等位基因提供了支持。
