64 research outputs found
A high occurrence of BRCA1 and BRCA2 mutations among Moravian hereditary breast and breast-ovarian cancer families
No full textBreast cancer is the most frequent malignancy diagnosed in women in the western world, affecting approximately 1 in 10 women. A family history of the disease in a first degree relative significantly increases the risk of cancer. Familial breast cancer is characterised by relatively young age at diagnoses, an increased risk of bilateral breast cancer, and a strong association with ovarian cancer. Germline mutations in highly penetrant autosomal dominant susceptibility genes BRCA1 and BRCA2, and probably other yet unknown genes could cause predisposition to these cancers. Molecular genetic testing of BRCA1 and BRCA2 genes in 21 high-risk breast and breast/ovarian cancer families was performed in order to find the types and the frequency of mutations in the South Moravian region of the Czech Republic. The mutation analysis was carried out on genomic DNA isolated from blood samples of affected individuals. As screening tests were used protein truncation test and heteroduplex analysis followed by direct sequencing. A germline disease-causing mutation was found in 12 of 21 tested families, 9 mutations in BRCA1 gene and 3 mutations in BRCA2 gene. The 5382insC in BRCA1 was found in four unrelated families. With regard to the occurrence of ovarian cancer, in12 families diagnosed with breast-only cancer syndrome 3 families harbouring BRCA1 mutation and 3 families harbouring BRCA2 mutation were detected. In 9 families with breast-ovarian cancer syndrome 6 families carrying BRCA1 mutation were detected. Molecular genetic testing of BRCA1 and BRCA2 genes in high-risk women with breast-ovarian cancer is effective in determining genetic predisposition to these cancer. A clearly disease-associated mutation was identified in either gene in 57 percents of screened families, proving that germline mutations in these breast cancer susceptibility genes might be responsible for an important fraction of inherited breast and ovarian cancer cases in Moravian region. Spectrum of mutations found in both genes is variable. The founder effect has been proven for 5382insC mutation in BRCA1 gene and further investigation is needed for estimation of other recurrent mutations in Moravian population. The genetic counselling and preventive clinical follow-up of gene carriers has to be part of the genetic programAvailable from STL Prague, CZ / NTK - National Technical LibrarySIGLECZCzech Republi
Mutation analysis of the BRCA1 and BRCA2 genes results in the identification of novel and recurrent mutations in 6/16 Flemish patients with breast and/or ovarian cancer but not in 12 sporadic patients with early-onset disease
No full textHigh occurrence of BRCA1 intragenic rearrangements in hereditary breast and ovarian cancer syndrome in the Czech Republic
No full textGenetic and Preventive Services for Hereditary Breast and Ovarian Cancer in the Czech Republic
No full textAbstract The majority of hereditary breast and ovarian cancers can be accounted for by germline mutations in the BRCA1 and BRCA2 genes. Genetic counselling and testing in high-risk patients in the Czech Republic began in 1997 in two centres (Masaryk Memorial Cancer Institute in Brno, MMCI, and the General University Hospital plus the First Faculty of Medicine, Charles University in Prague, 1FMUK). Health insurance covers testing in MMCI, whereas testing at 1FMUK is covered by research grants. The spectrum of mutations in the BRCA1 gene is similar in the Bohemian (western) and Moravian (eastern) regions of the country but the mutation spectrum observed in the BRCA2 gene is completely different. There are three BRCA1 gene mutations that are responsible for 69% and 70.4% of all BRCA1 mutations identified in women reporting to the Brno and Prague centres, respectively. The two most frequent mutations in the BRCA2 gene, which comprises 41.5% of all detected BRCA2 mutations in Brno, were not found in women tested in the Prague centre. The testing of BRCA1/BRCA2 or other possible predisposition genes for hereditary breast/ovarian cancer is determined by medical geneticists after genetic counselling. Predictive testing is offered to persons older than 18 years of age. Genetic counselling centres are easily accessible to all inhabitants in the country. Specialized preventive care is mostly organized by MMCI and the General University Hospital in Prague; however, some patients and their family members are under the care of other oncology departments and clinics. The quality of preventive care in different hospitals is currently being investigated.</p
Spectrum and characterisation of <it>BRCA1 </it>and <it>BRCA2 </it>deleterious mutations in high-risk Czech patients with breast and/or ovarian cancer
No full textAbstract Background The incidence of breast cancer has doubled over the past 20 years in the Czech Republic. Hereditary factors may be a cause of young onset, bilateral breast or ovarian cancer, and familial accumulation of the disease. BRCA1 and BRCA2 mutations account for an important fraction of hereditary breast and ovarian cancer cases. One thousand and ten unrelated high-risk probands with breast and/or ovarian cancer were analysed for the presence of a BRCA1 or BRCA2 gene mutation at the Masaryk Memorial Cancer Institute (Czech Republic) during 1999–2006. Methods The complete coding sequences and splice sites of both genes were screened, and the presence of large intragenic rearrangements in BRCA1 was verified. Putative splice-site variants were analysed at the cDNA level for their potential to alter mRNA splicing. Results In 294 unrelated families (29.1% of the 1,010 probands) pathogenic mutations were identified, with 44 different BRCA1 mutations and 41 different BRCA2 mutations being detected in 204 and 90 unrelated families, respectively. In total, three BRCA1 founder mutations (c.5266dupC; c.3700_3704del5; p.Cys61Gly) and two BRCA2 founder mutations (c.7913_7917del5; c.8537_8538del2) represent 52% of all detected mutations in Czech high-risk probands. Nine putative splice-site variants were evaluated at the cDNA level. Three splice-site variants in BRCA1 (c.302-3C>G; c.4185G>A and c.4675+1G>A) and six splice-site variants in BRCA2 (c.475G>A; c.476-2>G; c.7007G>A; c.8755-1G>A; c.9117+2T>A and c.9118-2A>G) were demonstrated to result in aberrant transcripts and are considered as deleterious mutations. Conclusion This study represents an evaluation of deleterious genetic variants in the BRCA1 and 2 genes in the Czech population. The classification of several splice-site variants as true pathogenic mutations may prove useful for genetic counselling of families with high risk of breast and ovarian cancer.</p
Differentiating pathogenic mutations from polymorphic alterations in the splice sites of BRCA1 and BRCA2
No full textEpidemiological, genetic, histological and clinical aspects of breast cancers in population of Czech women
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