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.

• Klíčová slova
• BRCA1, BRCA2, Breast cancer, Gene, Genetics, NGS,
• MeSH
• checkpoint kinasa 2 genetika   MeSH
• DNA vazebné proteiny genetika   MeSH
• dospělí MeSH
• genetická predispozice k nemoci MeSH
• genetické testování MeSH
• geny BRCA1 fyziologie   MeSH
• geny BRCA2 fyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mutace MeSH
• mutační rychlost * MeSH
• nádory prsu epidemiologie   genetika   MeSH
• nádory vaječníků epidemiologie   genetika   MeSH
• protein BRCA1 genetika   MeSH
• protein BRCA2 genetika   MeSH
• protein FANCN genetika   MeSH
• prsy patologie   MeSH
• tumor supresorové geny fyziologie   MeSH
• zárodečné mutace genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Názvy látek
• BRCA1 protein, human MeSH Prohlížeč
• BRCA2 protein, human MeSH Prohlížeč
• checkpoint kinasa 2 MeSH
• CHEK2 protein, human MeSH Prohlížeč
• DNA vazebné proteiny MeSH
• PALB2 protein, human MeSH Prohlížeč
• protein BRCA1 MeSH
• protein BRCA2 MeSH
• protein FANCN MeSH
• xeroderma pigmentosum group F protein MeSH Prohlížeč