Couch F J, Weber B L
Department of Medicine, University of Pennsylvania, Philadelphia 19104, USA.
Hum Mutat. 1996;8(1):8-18. doi: 10.1002/humu.1380080102.
Mutations in the familial early-onset breast cancer gene (BRCA1) account for approximately 2-5% of all breast cancer cases (Easton et al., 1993). Since the isolation of the BRCA1 gene in 1994, many mutations have been identified. We report here a total of 254 BRCA1 mutations, 132 (52%) of which are unique. These represent mutations entered into a database established by the Breast Cancer Information Core (BIC), which have appeared in the literature or have been submitted by BIC members and other contributors prior to publication. A total of 221 (87%) of all mutations or 107 (81%) of the unique mutations are small deletions, insertions, nonsense point mutations, splice variants, and regulatory mutations that result in truncation or absence of the BRCA1 protein. A total of 11 disease-associated missense mutations (5 unique), and 21 variants (19 unique) as yet unclassified as either missense mutations or polymorphisms have been detected. Thirty-five independent benign polymorphisms are also described. The most common mutations are 185delAG and 5382insC, which account for 30 (11.7%) and 26 (10.1%), respectively, of all mutations shown. The biological and clinical relevance of these BRCA1 mutations is discussed.
家族性早发型乳腺癌基因（BRCA1）的突变约占所有乳腺癌病例的2 - 5%（伊斯顿等人，1993年）。自1994年BRCA1基因被分离以来，已鉴定出许多突变。我们在此报告了总共254个BRCA1突变，其中132个（52%）是独特的。这些代表了录入乳腺癌信息核心（BIC）建立的数据库中的突变，这些突变已出现在文献中，或在发表前由BIC成员和其他贡献者提交。所有突变中的221个（87%）或独特突变中的107个（81%）是小缺失、插入、无义点突变、剪接变体和调节性突变，这些会导致BRCA1蛋白截短或缺失。已检测到总共11个与疾病相关的错义突变（5个独特），以及21个尚未归类为错义突变或多态性的变体（19个独特）。还描述了35个独立的良性多态性。最常见的突变是185delAG和5382insC，分别占所示所有突变的30个（11.7%）和26个（10.1%）。讨论了这些BRCA1突变的生物学和临床相关性。
