Smith L D, Tesoriero A A, Ramus S J, Dite G, Royce S G, Giles G G, McCredie M R E, Hopper J L, Southey M C
Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Vic., Australia.
Eur J Cancer. 2007 Mar;43(5):823-7. doi: 10.1016/j.ejca.2007.01.011. Epub 2007 Feb 21.
Women diagnosed with breast cancer before the age of 40 years who have a strong family history of breast and/or ovarian cancer were selected from an Australian population-based case-control-family study for large deletion screening within the BRCA1 promoter. Deletions within the BRCA1 promoter region are usually not detected by the methods applied in routine clinical mutation detection strategies. Fifty-one of the 66 women (77%) who met our inclusion criteria were tested for promoter deletions using linkage disequilibrium analysis of two BRCA1 polymorphic sites (C/G1802 and Pro871Leu) and multiplex ligation-dependent probe amplification. Two cases of BRCA1 promoter deletion involving exons 1A-2 and exons 1A-23 were detected. The morphology of the breast cancers arising in these women with BRCA1 promoter deletions was consistent with the morphology associated with other germline BRCA1 mutations. Large genomic deletions that involve the promoter regions of BRCA1 make up 20% (2/10) of all known BRCA1 mutations in this group of young women with a strong family history of breast and ovarian cancer. Our data support the inclusion of testing for large genomic alterations in the BRCA1 promoter region in routine clinical mutation detection within BRCA1.
从一项基于澳大利亚人群的病例对照家系研究中选取了40岁前被诊断为乳腺癌且有乳腺癌和/或卵巢癌家族史的女性，对她们进行BRCA1启动子区域的大片段缺失筛查。BRCA1启动子区域的缺失通常无法通过常规临床突变检测策略中应用的方法检测到。在符合我们纳入标准的66名女性中，有51名（77%）使用两个BRCA1多态性位点（C/G1802和Pro871Leu）的连锁不平衡分析和多重连接依赖探针扩增法检测启动子缺失。检测到2例涉及外显子1A - 2和外显子1A - 23的BRCA1启动子缺失。这些发生BRCA1启动子缺失的女性所患乳腺癌的形态与其他种系BRCA1突变相关的形态一致。在这组有乳腺癌和卵巢癌家族史的年轻女性中，涉及BRCA1启动子区域的大片段基因组缺失占所有已知BRCA1突变的20%（2/10）。我们的数据支持在BRCA1的常规临床突变检测中纳入BRCA1启动子区域大片段基因组改变的检测。
