Comprehensive analysis of 989 patients with breast or ovarian cancer provides BRCA1 and BRCA2 mutation profiles and frequencies for the German population
Comprehensive analysis of 989 patients with breast or ovarian cancer provides BRCA1 and BRCA2 mutation profiles and frequencies for the German population
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DOI：
10.1002/ijc.1626
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发表时间：
2002-02-01
影响因子：
6.4
通讯作者：
Weber, BHF
中科院分区：
文献类型：
--
作者：
Hofmann, W;Scherneck, S;Weber, BHF
这项德国范围内的多中心研究的主要重点是建立BRCA1/2突变谱，并确定这些基因突变频率高的家庭类型。在一项综合研究中，对来自德国乳腺癌/卵巢癌家族的989名不相关患者的乳腺癌基因BRCA1和BRCA2的整个编码序列进行了分析。在302例患者中共发现77种BRCA1和63种BRCA2不同的有害突变。这些突变中超过1/3是新的，可能是德国人特有的。在68%的BRCA1病例中发现18个常见突变，在44%的BRCA2病例中发现13个复发突变，促进了预筛查方法。单倍型分析表明，20个复发突变中有14个可能来自一个共同的创始人。另外在72个家族中发现了50种与肿瘤发生相关性未知的罕见序列变异。BRCA1/BRCA2检出率与家族史的相关性表明，同时患有乳腺癌和卵巢癌的家庭BRCA1/BRCA2突变的风险最高（分别为43%和10%），其次是至少有2例绝经前乳腺癌的家庭（24% BRCA1和13% BRCA2突变）。这些数据为进一步研究德国人群中的易感基因提供了强有力的证据。在有2或3名女性受影响但只有一个或没有绝经前病例的乳腺癌家族中，检测到的突变频率很低（两种基因的突变频率约为10%或更低）。现在，支持或反对分子诊断的决定是通过考虑预期的突变检出率来辅助的，这在很大程度上取决于家族史和结构。(C) 2002 Wiley-Liss, Inc。
The main focus of this German-wide multi-center study was to establish a BRCA1/2 mutation profile and to determine family types with high frequencies of mutations in these genes. In a comprehensive study, the entire coding sequences of the breast cancer genes BRCA1 and BRCA2 were analyzed in 989 unrelated patients from German breast/ovarian cancer families. A total of 77 BRCA1 and 63 BRCA2 distinct deleterious mutations were found in 302 patients. More than 1/3 of these mutations are novel and might be specific for the German population. Eighteen common mutations were found in 68% of cases in BRCA1 and 13 recurrent mutations in 44% of cases in BRCA2, facilitating prescreening approaches. Haplotype analysis indicate that 14 out of 20 recurrent mutations are likely originating from a common founder. An additional 50 different rare sequence variants with unknown relevance for tumorigenesis were found in 72 families. Correlation of BRCA1/BRCA2 detection rates with family history identified families with both breast and ovarian cancer to be at highest risk for BRCA1/BRCA2 mutations (43% and 10%, respectively), followed by families with at least 2 premenopausal cases of breast cancer (24% BRCA1 and 13% BRCA2 mutations). These data provide strong evidence for further predisposing genes in the German population. In breast cancer families with 2 or 3 affected females but only a single or no premenopausal case, mutations were detected with low frequencies (about 10% or less for both genes). The decision for or against molecular diagnosis is now aided by considering the expected mutation detection rates that greatly depend on family history and structure. (C) 2002 Wiley-Liss, Inc.