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.

• Keywords
• BRCA1, BRCA2, Breast cancer, Gene, Genetics, NGS,
• MeSH
• Checkpoint Kinase 2 genetics   MeSH
• DNA-Binding Proteins genetics   MeSH
• Adult MeSH
• Genetic Predisposition to Disease MeSH
• Genetic Testing MeSH
• Genes, BRCA1 physiology   MeSH
• Genes, BRCA2 physiology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Mutation MeSH
• Mutation Rate * MeSH
• Breast Neoplasms epidemiology   genetics   MeSH
• Ovarian Neoplasms epidemiology   genetics   MeSH
• BRCA1 Protein genetics   MeSH
• BRCA2 Protein genetics   MeSH
• Fanconi Anemia Complementation Group N Protein genetics   MeSH
• Breast pathology   MeSH
• Genes, Tumor Suppressor physiology   MeSH
• Germ-Line Mutation genetics   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic epidemiology   MeSH
• Names of Substances
• BRCA1 protein, human MeSH Browser
• BRCA2 protein, human MeSH Browser
• Checkpoint Kinase 2 MeSH
• CHEK2 protein, human MeSH Browser
• DNA-Binding Proteins MeSH
• PALB2 protein, human MeSH Browser
• BRCA1 Protein MeSH
• BRCA2 Protein MeSH
• Fanconi Anemia Complementation Group N Protein MeSH
• xeroderma pigmentosum group F protein MeSH Browser