Breast cancer is currently the most common form of malignant tumour in womenboth in the Czech Republic and in most countries of the western world, and its incidence is constantly increasing. Many risk factors are known to play a major role in the development of this form of cancer. One of them is genetics, especially the BRCA1/2 genes. A higher risk of ovarian cancer is also associated with these genes. With the development of laboratory diagnostics massive parallel sequencing methods (NGS) are now routinely employed, enabling the detection of other pathogenic sequence variants, or variants of uncertain significance (VUS) not previously detected. Besides the high penetrance BRCA1/2 genes, medium and low penetrant genes also come to the fore. There were 2046 probands examined in the study, men and women, mainly from eastern part of the Czech Republic. These were selected for a genetic examination, after meeting indication criteria (probands from high-risk families or with breast or ovarian cancer). From this group only women, 2033 probands, were selected and were given a genetic examination for the possible presence of patogenic sequence variants in BRCA1/2 genes, or other candidate genes. Analyses were conducted in the laboratory using DHPLC or next generation sequencing. MLPA method is used for large rearrangements in genes. From all examined women 212 mutations were detected. The most mutations (128) were found in the BRCA1 gene (60%). In the BRCA2 gene 71 mutations (34%) were found and 13 more mutations (6%) were detected in another candidate genes (CHEK2, PALB2, ERCC4). The most frequent sequence variant was c.5266dupC in the BRCA1 gene. The results show that 72% of women with a confirmed mutation in the BRCA1 gene and 77.5% of women with the sequence variant BRCA2, already had breast cancer and 16.4% of women with BRCA1 and 7% of women with BRCA2 already had ovarian cancer. Only 21 high risk families used the possibility to be tested and had undergone targeted mutation testing. The study results suggest a reflection of the causes and needs for examination of patients and women predisposed to breast or ovarian cancer.

中文翻译：

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在捷克共和国，高风险先证者或患有乳腺癌或卵巢癌的先证者中，BRCA基因和其他候选基因的突变频率。

乳腺癌是目前在捷克共和国和西方世界大多数国家中女性中最常见的恶性肿瘤形式，并且其发病率一直在增加。已知许多危险因素在这种形式的癌症的发展中起主要作用。其中之一是遗传学，尤其是BRCA1 / 2基因。这些基因也与卵巢癌的高风险有关。随着实验室诊断技术的发展，现在通常采用大规模并行测序方法（NGS），从而能够检测其他病原体序列变异体或以前未检测到的不确定性变异体（VUS）。除了高渗透率的BRCA1 / 2基因外，中低渗透率的基因也应运而生。研究中检查了2046名先证者，无论男女，主要来自捷克共和国东部。在符合适应症标准（来自高危家庭或患有乳腺癌或卵巢癌的先证者）后，将其选择进行基因检查。从这一组中，只选择了2033名先证者，并对其进行了遗传学检查，以了解BRCA1 / 2基因或其他候选基因中是否可能存在patogenic序列变异。在实验室中使用DHPLC或下一代测序进行分析。MLPA方法用于基因的大量重排。从所有接受检查的女性中检测到212个突变。在BRCA1基因中发现最多的突变（128）（60％）。在BRCA2基因中发现了71个突变（34％），在另一个候选基因（CHEK2，PALB2，ERCC4）中又检测到13个突变（6％）。最常见的序列变异是BRCA1基因中的c.5266dupC。结果显示，已确证BRCA1基因突变的女性中有72％和具有BRCA2序列变异的女性中有77.5％已经患有乳腺癌，有BRCA1的女性中有16.4％，有BRCA2的女性中有7％已经患有卵巢癌。只有21个高风险家庭使用了被测试的可能性，并进行了定向突变测试。研究结果表明，对易患乳腺癌或卵巢癌的患者和女性进行检查的原因和需求得到了反映。