Browsing by Subject "Breast Neoplasms--Familial and genetics."

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Open Access
Analysis of BRCA1 and BRCA2 genes in Turkish breast cancer patients
(2000) Özdağ, Hilal
Breast cancer is the most frequent cancer type and the second cause of death among women. It is estimated that 10 to 15% of breast cancer cases are hereditary. The majority of hereditary breast cancers can be attributed to germ-line mutations in ^Jgeast CAncer susceptibility genes BRCAl and BRCA2. In this study, germ-line BRCAl and/or BRCA2 gene mutations were screened in 50 Turkish breast and/or ovarian cancer patients divided into four groups of hereditary, familial, early onset, and male cancer by heteroduplex analysis and DNA sequencing. Two BRCA2 mutations, one novel (6880insG) and one previously reported (3034delAAAC), were found in the hereditary group. A novel BRCAl (1200insA) mutation was formd in the early onset group. All three mutations cause premature- termination codons. In addition, five BRCAl sequence variants have been identified in 23 patients. K654E (2080 A—>G), D693N (2196 G->A), P871L (2731 C—>T), and K1183R (3667 A—>G) result in a change of amino acids. 1013 T—^>C and 2201 C—>T are silent mutations. One patient in the early onset group was compound heterozygote for K654E and D693N. These results indicate that BRCAl and BRCA2 genes are involved in some but not all hereditary breast cancers in the Turkish population.
Open Access
Development of a non-immunological system for the study of the cellular localization of BRCA1 gene product in living cells
(1997) Çağatay, Tolga
BRCAl, is a familial breast and ovarian cancer susceptibility gene that has been cloned and shown to be either lost or mutated in families with breast and ovarian cancer. BRCAl, has been postulated to encode a tumor suppressor, a protein that acts as a negative regulator of tumor growth. To explore the biolo^cal function of BRCAl, several studies have been performed for the identification of cellular localization of BRCAl gene product. Results obtained from these immunofluorescent/ immunohistochemical studies generated two opposing views, cytoplasmic localization versus nuclear localization. Here, we describe a non-immunological system employing the Eukaiyotic Green fluorescent Protein (EGFP) tag for the study of the cellular localization of BRCAl gene product in living cells. Proteins carrying the green fluorescent protein (GFP) of Aequorea victoria provide a powerful system to analyze protein expression and targeting in living cells. Fusion proteins containing the GFP tag are therefore valuable tools to analyze nuclear trafficking in living cells. Here, we reporte the use of a mutant GFP, namely Eukaryotic Green Fluorescent Protein (EGFP), as a marker for the protein import into mammalian nuclei. We have analyzed the behavior of a protein domain of the BRCAl, that contains five putative nuclear localization signals (NLSs), in vivo using a chimera constructed from this polypeptide and the EGFP. This in vivo studies showed that EGFP was distributed uniformly throughout the cytoplasm and the nucleus. When EGFP was fused to NLSs containing domain of the BRCAl protein, fluorescent was predominantly detected in the nucleus, showing that these potential NLSs consensus sequences may destínate the full-lengh BRCAl producy into the nucleus of mammalian cell. This study has also shown that EGFP can be used as a potential fluorescent tag for visualization of gene expression and cellular protein localization in living cells.
Open Access
Establishment of a rapid mutation detection technique for screening of BRCA1 and BRCA2 genes
(1997) Öktem, Emre
People bearing germline mutations in either BRCAl or BRCA2 genes are more prone to breast cancer than other people. These two recently identified genes account for nearly 90% of the hereditary cancer cases. This number corresponds approximately to 100,000 women each year in Turkey. The individuals who carry these mutations are at high risk and characterizing these mutations will be helpful for providing them genetic counseling. This includes the estimation of risk for both the individual and his/her progeny. In addition, discovering the mutations is an important step in finding out the iunctions of these genes, which will give insights about how breast cancer is occurring In this study, we have established an easy and rapid mutation detection strategy; heteroduplex analysis, and tested its efficiency in 15 hereditary breast cancer patients. These patients have been screened for the entire exon 11 of BRCAl, which is 50% o f the entire coding region. In addition, half of the exon 11 of BRCA2, which is roughly one fourth of the coding region was examined in 10 patients. As yet, no mutation in the Turkish patients have been encountered These results exclude exon 11 of the BRCAl gene and part of exon 11 of the BRCA2 gene for nucleotide deletions and insertions as the cause of hereditary breast cancer in Turkey. In order to verily the efficiency of the technique, we have also screened four French hereditary breast cancer patients with previously characterized BRCAl mutations in exon 11, and confirmed the presence o f the mutations in the majority o f the cases With the technique, firmly established in our laboratory, we plan to analyze the remaining coding regions of the BRCAl and BRCA2 genes in our patient samples and in additional patients.