New sequence variants in BRCA1 and BRCA2 genes detected by high-resolution melting analysis in an elderly healthy female population in Croatia
New sequence variants in BRCA1 and BRCA2 genes detected by high-resolution melting analysis in an elderly healthy female population in Croatia
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DOI：
10.1515/cclm.2008.307
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发表时间：
2008-10-01
影响因子：
6.8
通讯作者：
Levanat, Sonja
中科院分区：
文献类型：
--
作者：
Cvok, Mirela Levacic;Cretnik, Maja;Levanat, Sonja
背景：BRCA1和BRCA2基因突变与乳腺癌和卵巢癌的家族易感性相关。为了高效、快速地检测癌症患者及其家庭成员的序列变异，需要新的筛查方法。方法：在克罗地亚，乳腺癌和卵巢癌易感基因BRCA1和BRCA2的变异通过高分辨率熔化法进行筛选，该方法基于核苷酸序列变化引起的熔化曲线差异。这是克罗地亚首次对没有癌症家族史的健康老年妇女进行筛查。对220个样本进行BRCA1筛查，对115个样本进行BRCA2筛查。结果：在远远超过乳腺癌/卵巢癌发病平均年龄的人群中，检测到21种不同的BRCA1基因序列变异（1种新的：c. 5193+49_50delTA）和36种BRCA2基因变异（7种新的：c. 459a > c, c. 3318c > a, c. 4412_4414delgaa, c. 4790c > a, c. 6264t > c, c. 9087g > a和c. 9864A > G）。结论：已知的9种BRCA1和7种BRCA2变异出现的频率如此之高，以至于可以宣布它们在该人群中是无害的。距离启动子区域较远的8种BRCA1高频变异似乎具有很强的相关性。三个改变BRCA2蛋白氨基酸序列的新变异（两个错义碱基替换，c. 3318C > A和c. 4790C > A，以及一个密码子缺失c. 4412_4414delGAA）仅出现一次，预计对蛋白质结构和功能没有潜在影响。
Background: Mutations in BRCA1 and BRCA2 genes are associated with family predisposition to breast and ovarian cancer. Novel screening methods are required for efficient and rapid detection of sequence variants in cancer patients and their family members.Methods: The screening for variants in the breast and ovarian cancer susceptibility genes BRCA1 and BRCA2 in Croatia was performed by a high-resolution melting approach, which is based on differences in melting curves caused by variations in nucleotide sequence. This is the first screening in Croatia on elderly healthy women with no family history of cancer. BRCA1 screening was performed on 220 and BRCA2 screening on 115 samples.Results: In a population well beyond the average age of breast/ovarian cancer onset, 21 different sequence variants in the BRCA1 gene (one novel: c. 5193+49_50delTA) and 36 variants in the BRCA2 gene (7 novel: c.459A > C, c.3318C > A, c.4412_4414delGAA, c.4790C > A, c.6264T > C, c.9087G > A, and c. 9864A > G) were detected.Conclusions: Nine BRCA1 and seven BRCA2 known variants appeared with such high frequencies that they could be declared as harmless in this population. Eight BRCA1 high frequency variants, located further from the promoter region, appear to be strongly correlated. Three novel variants that changed the amino acid sequence of the BRCA2 protein (two missense base substitutions, c. 3318C > A and c. 4790C > A, and one codon deletion c. 4412_4414delGAA), appearing only once, were predicted to have no potential effect on protein structure and function.