German family study on hereditary breast and/or ovarian cancer: Germline mutation analysis of the BRCA1 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>3.3.co;2-o

Cited by 8 publications

(14 citation statements)

References 18 publications

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“…SSCP and PTT analysis was performed as previously described [16,17]. DHPLC analysis was performed using the WAVE system (Transgenomics, Omaha, NE, USA).…”

Section: Mutation Screeningmentioning

confidence: 99%

High proportion of BRCA1/2 founder mutations in Hispanic breast/ovarian cancer families from Colombia

Torres

Rashid

Gil

et al. 2006

Breast Cancer Res Treat

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106

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In South America, a high proportion of the population is of Hispanic origin with an important representation in Colombia. Since nothing is known about the contribution of BRCA1 and BRCA2 germline mutations to hereditary breast/ovarian cancer in the Hispanic population from Colombia, we conducted the first study of 53 breast/ovarian cancer families from this country. Comprehensive BRCA mutation screening was performed using a range of techniques, including DHPLC, SSCP, and PTT, followed by DNA sequencing analysis. Thirteen deleterious germline mutations (24.5%) were identified in 53 families, comprising eight in BRCA1 and five in BRCA2. The two recurrent BRCA1 mutations, 3450 delCAAG and A1708E, accounted for 100% of all BRCA1 mutations identified in this cohort and the recurrent 3034 delACAA BRCA2 mutation for 40% of all BRCA2 mutations. Haplotype analyses suggested that each of these mutations has arisen from a common ancestor. The prevalence of BRCA1 or BRCA2 mutations was 50% in multiple case breast cancer families, and was 33% for the breast-ovarian cancer families. Our findings show that BRCA mutations account for a substantial proportion of hereditary breast/ovarian cancer in Colombia. The spectrum of mutations differed completely to that previously reported in Hispanic families of predominantly Mexican origin from Southern California [1] suggesting that specific genetic risk assessment strategies for the different Hispanic populations in South America and in the United States need to be developed.

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“…SSCP and PTT analysis was performed as previously described [16,17]. DHPLC analysis was performed using the WAVE system (Transgenomics, Omaha, NE, USA).…”

Section: Mutation Screeningmentioning

confidence: 99%

High proportion of BRCA1/2 founder mutations in Hispanic breast/ovarian cancer families from Colombia

Torres

Rashid

Gil

et al. 2006

Breast Cancer Res Treat

Self Cite

106

View full text Add to dashboard Cite

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“…16 There are to date no comprehensive studies in the German population where most studies have been limited to the analysis of BRCA1 or to relatively small series. [17][18][19][20] In 1996, the Deutsche Krebshilfe supported the formation of a research collaboration, the "German Consortium for Hereditary Breast and Ovarian Cancer," to establish a national network for the management and treatment of women with a familial predisposition to breast and ovarian cancer. This long-term project is multifaceted and includes the collection of genetic, gynecological and psychological data regarding BRCA1 and BRCA2 testing.…”

mentioning

confidence: 99%

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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“…Probands from families harbouring BRCA2 germline mutations (n=7) were significantly younger than probands from BRCA1/2 negative families (n=58) with a median age at diagnosis of breast cancer of 36 years and 44.5 years, respectively (Wilcoxon rank sum test, p=0.03). There was no difference in the age of breast cancer diagnosis of probands of BRCA1 families (n=13), median age of 37 years, [17][18][19] from probands of BRCA2 families (Wilcoxon rank sum test, p=0.98).…”

Section: Brca2 Germline Mutationsmentioning

confidence: 93%

“…Sixty-one of these families have been described previously. 17 18 20 Seven additional breast cancer families that fit the ascertainment criteria were also screened for BRCA1 mutations and found not to harbour any changes in this gene (U Hamann, unpublished data). BRCA1 mutation detection was performed using single strand conformational polymorphism analysis (SSCP) for all small coding exons, and the protein truncation test (PTT) for exon 11, followed by DNA sequencing analysis of all unusual conformers or prematurely truncated proteins.…”

Section: Familiesmentioning

confidence: 99%

“…14 15 In Germany, 18% of the breast/ovarian cancer families are the result of BRCA1 germline mutations. [16][17][18][19] To determine the contribution of BRCA2 to hereditary breast/ovarian cancer, we have performed a systematic study of the BRCA2 gene in a series of 68 BRCA1 negative breast/ovarian cancer families by using a combination of single strand conformational polymorphism analysis (SSCP) and the protein truncation test (PTT) followed by DNA sequencing analysis.…”

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confidence: 99%

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Contribution of BRCA2 germline mutations to hereditary breast/ovarian cancer in Germany

Hamann

2002

Journal of Medical Genetics

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Breast cancer is the most common malignancy affecting women world wide.1 Approximately 1 in 10 women will develop breast cancer during their life time 2 and 5-10% of all breast cancers, in particular those with an early age of onset, are the result of a genetic predisposition owing to the inheritance of a dominant susceptibility gene(s).In the context of high risk families, one important gene is the BRCA2 gene located on chromosome 13q12-13. BRCA2 was localised to chromosome 13q by linkage analysis in 1994 3 and cloned in 1995.4 5 To date, more than 250 BRCA2 germline mutations have been identified in breast/ovarian cancer families. 6 The majority of these mutations are nonsense mutations or frameshift mutations that generate premature termination codons.7 Recent studies on highly selected families with at least four cases of breast cancer suggest that BRCA2 accounts for the majority of breast cancer families where males as well as females are affected, for about one third of the families with female breast cancer alone, and only for a few families containing multiple cases of breast and ovarian cancer.8 BRCA2 encodes a nuclear protein of 3418 amino acid residues that is postulated to play a role in the regulation of gene expression 9 and in DNA double strand break repair and homologous recombination. 10Estimates of the cumulative breast cancer risks by the age of 70 in BRCA2 mutation carriers vary from 37-85% 8 11 and the cumulative ovarian cancer risks from 16-27%.8 12 There is evidence for an increased risk of several other cancers including prostate cancer, pancreatic cancer, gall bladder and bile duct cancer, stomach cancer, and malignant melanoma.13 Analyses of BRCA2 mutation data have provided evidence that the risks of breast cancer and ovarian cancer are related to the position of the mutation. Truncating mutations in families with the highest risk of ovarian cancer relative to breast cancer are clustered in the Ovarian Cancer Cluster Region (OCCR) in exon 11. 14 15 In Germany, 18% of the breast/ovarian cancer families are the result of BRCA1 germline mutations. [16][17][18][19] To determine the contribution of BRCA2 to hereditary breast/ovarian cancer, we have performed a systematic study of the BRCA2 gene in a series of 68 BRCA1 negative breast/ovarian cancer families by using a combination of single strand conformational polymorphism analysis (SSCP) and the protein truncation test (PTT) followed by DNA sequencing analysis. METHODS FamiliesPatients were identified through an ongoing research family study of hereditary breast/ovarian cancer recruiting families from all over Germany. Families containing three or more members affected with breast/ovarian cancer with at least two breast cancer cases diagnosed under the age of 60 years and ovarian cancer diagnosed at any age were ascertained through gynaecologists or in response to press publicity in Germany. Each pedigree was extended through an index case and available related family members. All participants gave informed consent and blood samples. B...

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German family study on hereditary breast and/or ovarian cancer: Germline mutation analysis of the BRCA1 gene

Cited by 8 publications

References 18 publications

High proportion of BRCA1/2 founder mutations in Hispanic breast/ovarian cancer families from Colombia

High proportion of BRCA1/2 founder mutations in Hispanic breast/ovarian cancer families from Colombia

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

Contribution of BRCA2 germline mutations to hereditary breast/ovarian cancer in Germany

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