Konecny M, Vizvaryova M, Weismanova E, Ilencikova D, Mlkva I, Weismann P, Machackova G, Kausitz J
Department of Clinical Genetics, St. Elizabeth Cancer Institute, Bratislava, Slovakia.
Neoplasma. 2007;54(2):137-42.
Pathogenic germline mutations in BRCA1 and BRCA2 account for the majority of hereditary breast/ovarian cancer cases. The analysis of BRCA1 gene was carried out in 156 breast/ovarian cancer families: 82 families with strong family history and 59 families with medium family history. Generally, 31 families and 71 cases with BRCA1 pathologic mutations (14 different types) were identified in this study by combination of SSCP and direct sequencing techniques. Using approved systematic nomenclature numbering, c.5266dupC (8 families, 21 cases), c.181T>G (5 families, 11 cases), c.68_69delAG (3 families, 5 samples) and c.843_846del4 (3 families, 4 samples) were the most frequently found mutations in BRCA1 gene. Altogether these 4 mutations accounted for 61.3% of all detected pathogenic mutations in BRCA1. One novel mutation c.1166delG was detected in one family (4 cases). Frame-shift mutations were found in 21 families (46 cases), nonsense mutations in 4 families (8 cases) and missense mutations in 6 families (17 cases). Even though the 4 most frequent mutations account for 61.3% of all detected pathogenic mutations, screening of the whole BRCA1 coding region is necessary, due to the large scale of low frequency disease causing mutations in breast/ovarian cancer families in Slovakia.
BRCA1和BRCA2的致病性种系突变占遗传性乳腺癌/卵巢癌病例的大多数。对156个乳腺癌/卵巢癌家族进行了BRCA1基因分析：82个有强烈家族病史的家族和59个有中度家族病史的家族。一般来说，本研究通过单链构象多态性（SSCP）和直接测序技术相结合，鉴定出31个家族和71例具有BRCA1病理突变（14种不同类型）的病例。使用批准的系统命名编号，c.5266dupC（8个家族，21例）、c.181T>G（5个家族，11例）、c.68_69delAG（3个家族，5个样本）和c.843_846del4（3个家族，4个样本）是BRCA1基因中最常发现的突变。这4种突变总共占BRCA1所有检测到的致病性突变的61.3%。在一个家族（4例）中检测到一种新的突变c.1166delG。在21个家族（46例）中发现了移码突变，在4个家族（8例）中发现了无义突变，在6个家族（17例）中发现了错义突变。尽管4种最常见的突变占所有检测到的致病性突变的61.3%，但由于斯洛伐克乳腺癌/卵巢癌家族中低频致病突变的规模较大，因此有必要对整个BRCA1编码区进行筛查。
