German family study on hereditary breast and/or ovarian cancer: Germline mutation analysis of theBRCA1 gene

Hamann, Ute; Brauch, Hiltrud; Garvin, Alex M.; Bastert, G.; Scott, Rodney J.

doi:10.1002/(sici)1098-2264(199702)18:2<126::aid-gcc7>3.0.co;2-4

Cited by 17 publications

(1 citation statement)

References 26 publications

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“…However, other analysis suggest that the actual incidence of BRCAl in high risk families (>3 cases of breast and/or ovarian cancer) might be as low as 12.8% to 16% [4]. Substantial variation in the prevalence of BRCA1 mutations in high risk families in various countries has been observed which are more common than BRCA2 mutations [16,17]. …”

Section: Introductionmentioning

confidence: 99%

Presymptomatic breast cancer in Egypt: role of BRCA1 and BRCA2 tumor suppressor genes mutations detection

Ibrahim

Hafez

Hashishe

2010

J Exp Clin Cancer Res

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BackgroundBreast cancer is one of the most common diseases affecting women. Inherited susceptibility genes, BRCA1 and BRCA2, are considered in breast, ovarian and other common cancers etiology. BRCA1 and BRCA2 genes have been identified that confer a high degree of breast cancer risk.ObjectiveOur study was performed to identify germline mutations in some exons of BRCA1 and BRCA2 genes for the early detection of presymptomatic breast cancer in females.MethodsThis study was applied on Egyptian healthy females who first degree relatives to those, with or without a family history, infected with breast cancer. Sixty breast cancer patients, derived from 60 families, were selected for molecular genetic testing of BRCA1 and BRCA2 genes. The study also included 120 healthy first degree female relatives of the patients, either sisters and/or daughters, for early detection of presymptomatic breast cancer mutation carriers. Genomic DNA was extracted from peripheral blood lymphocytes of all the studied subjects. Universal primers were used to amplify four regions of the BRCA1 gene (exons 2,8,13 and 22) and one region (exon 9) of BRCA2 gene using specific PCR. The polymerase chain reaction was carried out. Single strand conformation polymorphism assay and heteroduplex analysis were used to screen for mutations in the studied exons. In addition, DNA sequencing of the normal and mutated exons were performed.ResultsMutations in both BRCA1 and BRCA2 genes were detected in 86.7% of the families. Current study indicates that 60% of these families were attributable to BRCA1 mutations, while 26.7% of them were attributable to BRCA2 mutations. Results showed that four mutations were detected in the BRCA1 gene, while one mutation was detected in the BRCA2 gene. Asymptomatic relatives, 80(67%) out of total 120, were mutation carriers.ConclusionsBRCA1 and BRCA2 genes mutations are responsible for a significant proportion of breast cancer. BRCA mutations were found in individuals with and without family history.

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Section: Introductionmentioning

confidence: 99%

Presymptomatic breast cancer in Egypt: role of BRCA1 and BRCA2 tumor suppressor genes mutations detection

Ibrahim

Hafez

Hashishe

2010

J Exp Clin Cancer Res

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Low incidence ofBRCA1 mutations among Italian families with breast and ovarian cancer

et al. 1998

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Most familial breast or ovarian cancers are thought to be due to highly penetrant mutations in the predisposing genes BRCA1 and BRCA2. The cloning of these genes has opened a new era for the genetic counseling of women with a family history of breast or ovarian cancer. To estimate the incidence of detectable BRCA1 mutations and to define the eligibility criteria for genetic testing in the Italian population, a total of 53 patients belonging to 46 families clustering multiple cases of breast and/or ovarian cancer were investigated. Seven families presented with ovarian cancer only, 16 had both ovarian and breast cancers, and 23 were characterized by breast cancer only. Using a combination of protein truncation test (PTT) and single strand conformational polymorphism (SSCP) analysis followed, when necessary, by direct sequencing, we found 8 distinct mutations, 2 of these not reported before. Five frameshift and 2 nonsense mutations led to a truncated protein. One mutation was a missense substitution involving a cysteine in the zinc finger domain. One variant creating an ETS binding site in intron 1 was found but its role was not defined. The percentage of families carrying mutations was 17%. Among the families characterized by ovarian cancer only and by breast and ovarian cancer, the percentage of BRCA1 mutations was 57% and 12.5%, respectively. In contrast, the percentage of altered BRCA1 in families with only breast cancers was 9%. In the 46 Italian families studied, BRCA1 mutations were detected in fewer kindreds than those previously hypothesized based on linkage analysis, especially when these were characterized by breast cancers only. Our results indicate that families with a low number of cancer patients should be referred for BRCA1 genetic testing mainly when ovarian cancer is present. Int. J. Cancer 78:581–586, 1998. © 1998 Wiley‐Liss, Inc.

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Comprehensive analysis of 989 patients with breast or ovarian cancer provides BRCA1 and BRCA2 mutation profiles and frequencies for the German population

2001

Intl Journal of Cancer

193

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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.

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German family study on hereditary breast and/or ovarian cancer: Germline mutation analysis of theBRCA1 gene

Cited by 17 publications

References 26 publications

Presymptomatic breast cancer in Egypt: role of BRCA1 and BRCA2 tumor suppressor genes mutations detection

Presymptomatic breast cancer in Egypt: role of BRCA1 and BRCA2 tumor suppressor genes mutations detection

Low incidence ofBRCA1 mutations among Italian families with breast and ovarian cancer

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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