BRCA1 mutations in German breast-cancer families

Jandrig, Burkhard; Grade, K; Seitz, Susanne; Waindzoch, Beate; Müller, Manuela; Bender, E.; Nothnagel, Anita; Rohde, Klaus; Schlag, Peter M.; Kath, R.; Höffken, K.; Scherneck, Siegfried

doi:10.1002/(sici)1097-0215(19961009)68:2<188::aid-ijc8>3.0.co;2-u

Cited by 18 publications

(9 citation statements)

References 16 publications

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“…LOHs in 17q21 have been reported in a variety of malignancies including breast (Cropp et al, 1993), ovary (Wertheim et al, 1996) and prostate cancers (Gao et (Sato et al, 1993). Recent positional cloning of the BRCA1 from that region and its mutation screening support that the BRCA1 is responsible for inherited breast (Jandrig et al, 1996) and ovarian cancer (Merajver et al, 1995). It would be interesting to screen for BRCA1 mutations in tumor samples which demonstrate LOH at the BRCA1 locus.…”

Section: Discussionmentioning

confidence: 99%

Loss of heterozygosity (LOH) at 17q and 14q in human lung cancers

et al. 1998

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Our recent linkage study of urethane-induced pulmonary adenomas in SMXA RI strains of mouse revealed two host resistance genes, Par1 (chromosome 11) and Par3 (chromosome 12). The map positions of Par1 and Par3 correspond to human 17q11-23 and 14q11-24, based on synteny between mouse and human. In this study, we examined the loss of heterozygosity (LOH) in these two homologous human chromosomal regions in 30 primary lung adenocarcinoma samples with matched normal DNA. Using 15 highly polymorphic markers, two commonly deleted regions were identi®ed on human chromosomes 14 and 17, respectively. At 17q21, nine (53%) of 17 informative tumors showed LOH between D17S588 and D17S518. On the other hand, at 14q11-12, seven (32%) of 22 informative tumors showed LOH at loci between D14S261 and D14S80. Subsequently, we examined 25 squamous cell carcinomas (SQ) and 24 small cell carcinomas (SCC). At 14q11-12, six (38%) of 16 informative SQ and ®ve (42%) of 12 informative SCC showed LOH. In contrast, at 17q11-23, one (7%) of 15 informative SQ and two (14%) of 14 SCC showed LOH. Therefore, the gene on 17q seemed to a ect selectively adenocarcinomas, whereas the other gene on 14q, all three types of lung carcinomas. These observations indicate that a comparative genetic analysis provides a promising approach to survey genes involved in multifactorial process of human lung carcinogenesis.

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Section: Discussionmentioning

confidence: 99%

Loss of heterozygosity (LOH) at 17q and 14q in human lung cancers

et al. 1998

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“…The amplification products were purified and run on SSCP gels at temperatures between 7 and 301C (SSCP buffer conditions as described) (Jandrig et al, 1996). PCR products showing mobility shifts were subjected to direct sequencing using ABI 377 sequencers.…”

Section: Mutation Analysismentioning

confidence: 99%

ST18 is a breast cancer tumor suppressor gene at human chromosome 8q11.2

et al. 2004

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We have identified a gene, ST18 (suppression of tumorigenicity 18, breast carcinoma, zinc-finger protein), within a frequent imbalanced region of chromosome 8q11 as a breast cancer tumor suppressor gene. The ST18 gene encodes a zinc-finger DNA-binding protein with six fingers of the C2HC type (configuration Cys-X 5 -Cys-X 12 -His-X 4 -Cys) and an SMC domain. ST18 has the potential to act as transcriptional regulator. ST18 is expressed in a number of normal tissues including mammary epithelial cells although the level of expression is quite low. In breast cancer cell lines and the majority of primary breast tumors, ST18 mRNA is significantly downregulated. A 160 bp region within the promoter of the ST18 gene is hypermethylated in about 80% of the breast cancer samples and in the majority of breast cancer cell lines. The strong correlation between ST18 promoter hypermethylation and loss of ST18 expression in tumor cells suggests that this epigenetic mechanism is responsible for tumor-specific downregulation. We further show that ectopic ST18 expression in MCF-7 breast cancer cells strongly inhibits colony formation in soft agar and the formation of tumors in a xenograft mouse model.

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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.…”

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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

190

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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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BRCA1 mutations in German breast-cancer families

Cited by 18 publications

References 16 publications

Loss of heterozygosity (LOH) at 17q and 14q in human lung cancers

Loss of heterozygosity (LOH) at 17q and 14q in human lung cancers

ST18 is a breast cancer tumor suppressor gene at human chromosome 8q11.2

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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