OBJECTIVETo study BRCA1 gene expression in sporadic breast cancer in Han nationality and its relations to clinical pathological parameters.

METHODSImmunohistochemical method was used to detect the BRCA1 protein in paraffin embedded breast cancer tissue of 51 patients. The relationship between BRCA1 protein and clinical pathological features was analysed.

RESULTSBRCA1 protein was located in the nuclear of breast cancer cells. The rate of its down regulation of expression was 49.0% (25/51), which correlated reversely with c-erbB-2 protein, but did not correlate with histological grading, tumor size, lymph node involvement and patient age.

CONCLUSIONThe detection of BRCA1 protein expression may be a reflection of its gene alteration. So it may be a primary method for screening the susceptibility to breast cancer.

Adult ; Aged ; BRCA1 Protein ; analysis ; Breast Neoplasms ; genetics ; pathology ; Female ; Genes, BRCA1 ; Humans ; Immunohistochemistry ; Middle Aged

Asian Continental Ancestry Group/genetics* ; BRCA1 Protein/genetics* ; China ; Consensus ; Humans

Asian Continental Ancestry Group ; BRCA1 Protein/genetics* ; Breast Neoplasms/surgery* ; China ; Female ; Genetic Testing ; Humans ; Mastectomy

OBJECTIVETo detect the mutation sites of exons 2, 20, 11A and 11B in Chinese patients with breast cancer.

METHODSA total of 86 patients with breast cancer without blood relationship were randomly selected. Polymerase chain reaction (PCR) and double-strand DNA direct sequencing were applied.

RESULTSNo mutations, especially deletions were found in exons 2, 20 and 11 with carefully checking the sequencing results, although they were reported frequently in Europe populations with breast cancer. We found one polymorphism in exon 11, with high frequency, and in the test of chi-square, the frequencies of two alleles had no significant difference between the patients and controls.

CONCLUSIONThe above results suggest this SNP may not be associated with the breast cancer in Chinese population, and indicates that the gene sequence of what we have studied doesn't account much for occurrence of the breast cancer in the population of China.

Asian Continental Ancestry Group ; genetics ; BRCA1 Protein ; genetics ; Breast Neoplasms ; genetics ; Exons ; Female ; Gene Frequency ; Humans ; Mutation ; Polymorphism, Genetic

OBJECTIVETo develop a method for ng quantitation of circulating DNA in serum and explore the value in the diagnosis of cancer.

METHODSSerum DNA was extracted by commercial "genomic DNA extraction kit" and detected by fluorescent dye (SYBR green I) staining. Loss of heterozygosity (LOH) at BRCA1 (D17S579, D17S855) and p53 (TP53, D17S786) in serum DNA was analyzed by PCR-based method.

RESULTSSYBR green I dot staining could detect DNA as low as 2 ng. Using this method, we detected serum samples from 483 patients with various types of cancer and 150 healthy individuals. The mean DNA concentration in the normal controls was 22.2 +/- 13.4 ng/ml, while that in cancer patients was 81.3 +/- 98.3 ng/ml (P < 0.001). In 33 ovarian cancer patients with increased DNA level, 27(81.8%) displayed LOH in at least one of the four loci analyzed.

CONCLUSIONCirculating DNA in serum may become additional tumor marker for the diagnosis of cancer.

BRCA1 Protein ; genetics ; Biomarkers, Tumor ; blood ; DNA, Neoplasm ; blood ; genetics ; Female ; Genes, BRCA1 ; Genes, p53 ; Humans ; Loss of Heterozygosity ; Male ; Microsatellite Repeats ; Neoplasms ; blood ; genetics ; Tumor Suppressor Protein p53 ; genetics

OBJECTIVE: To detect potential variant in an ethical Han Chinese pedigree affected with breast cancer. METHODS: The proband and her relatives were subjected to next-generation sequencing using a target capture sequencing kit containing 121 cancer-related genes. Candidate variants were selected by analysis of their type, frequency in population, and segregation with the phenotype. Candidate variant was verified by Sanger sequencing and TA cloning. RESULTS: A c.2013_2014ins GT variant was detected in the BRCA1 gene among all breast cancer patients from this pedigree but not among healthy females. The variant was not recorded in the 1000 Genome Project database or the Exome Aggregation Consortium (ExAC) database. The frameshifting insertion was predicted to form an premature stop codon in gene transcript and can give rise to a truncated protein. CONCLUSION The BRCA1 c.2013_2014ins GT variant probably underlies the pathogenesis of breast cancer in this Chinese pedigree.
Asian Continental Ancestry Group ; BRCA1 Protein ; genetics ; Breast Neoplasms ; genetics ; Exome ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; Pedigree ; Phenotype

OBJECTIVETo investigate the prevalence of BRCA1 and BRCA2 gene mutations among breast cancer patients with affected relatives in Shanghai of China.

METHODSThirty-five breast cancer patients who had at least one first-degree relative affected were analyzed, among whom 13 patients suffered from breast cancer at age of less than 40 years. A comprehensive BRCA1 and BRCA2 mutation analysis was performed through denaturing high-performance liquid chromatography (DHPLC) and subsequent DNA direct sequencing.

RESULTSFour mutations in BRCA1 gene, including 2 novel splice-site mutations (IVS17-1G>T, IVS21+1G>C) and 2 frameshift mutations (1100delAT; 5640delA) were identified. One frameshift mutation (5802delAATT) was detected in exon 11 of BRCA2. Additional 12 novel single nucleotide polymorphisms(SNPs) were detected, including a novel unclassified variant and 7 novel intronic variants in BRCA1, and 4 novel intronic variants in BRCA2, with which all caused no alteration of amino acid coding. The mutation frequency of BRCA1 and BRCA2 in patients with family history was 11.4% and 2.9%, respectively.

CONCLUSIONTwo novel mutations in BRCA1 may be mutations characterized to familial breast cancer of Chinese Shanghai population. The BRCA2 may contribute to mutation less than BRCA1 in familial breast cancer. Our data contribute to information on mutation spectrum of BRCA gene in Chinese population and also offer a recommended screening mode for clinical genetic testing policy in China.

Asian Continental Ancestry Group ; genetics ; BRCA1 Protein ; genetics ; BRCA2 Protein ; genetics ; Breast Neoplasms ; genetics ; China ; DNA, Neoplasm ; analysis ; Family Health ; Female ; Humans ; Point Mutation ; Polymorphism, Single Nucleotide

Good progress has been made in the researches on correlating genes of breast cancer in recent years. Quite a few kinds of genes such as susceptibility gene, oncogene and tumor suppressor genes have been found with implications for diagnosis, therapy and prognosis. Abnormality of breast cancer susceptibility gene (BRCA) is of great significance, especially in the development of breast cancer.
BRCA1 Protein ; genetics ; BRCA2 Protein ; genetics ; Breast Neoplasms ; genetics ; Cyclin-Dependent Kinase Inhibitor p16 ; genetics ; Cyclin-Dependent Kinase Inhibitor p21 ; Cyclins ; genetics ; Female ; Humans ; Mutation ; Neoplasm Proteins ; genetics ; Proto-Oncogene Proteins ; genetics ; Tumor Suppressor Protein p53 ; genetics

OBJECTIVETo study the BRCA1 mutations in Chinese patients with early onset breast cancer and affected relatives.

METHODSGenomic DNA from 41 patients' peripheral blood mononuclear cells was studied by using polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) and DNA sequencing. BRCA1 mutations were detected in the whole gene sequence.

RESULTSDisease-related BRCA1 mutations were detected in 3 of the 41 patients studied. Two of the 3 patients were younger than 35 years old, and one patient with family history.

CONCLUSIONThe incidence of BRCA1 mutations in Chinese patients with early onset breast cancer is similar to that reported from western countries, but the incidence of mutations in Chinese breast cancer patients with affected relatives is comparatively low.

Adult ; Age of Onset ; BRCA1 Protein ; genetics ; Breast Neoplasms ; genetics ; China ; DNA Mutational Analysis ; DNA, Neoplasm ; blood ; Exons ; Female ; Genes, BRCA1 ; Humans ; Leukocytes, Mononuclear ; chemistry ; Mutation ; Polymerase Chain Reaction ; Polymorphism, Single-Stranded Conformational

OBJECTIVETo investigate the role of the tumor suppressor gene BRCA1 in response to DNA damage and to confirm that the function of the BRCA1 protein is regulated by a variety of mechanisms including transcriptional control, phosphorylation and protein-protein interaction.

METHODSWith the human breast cell line MCF7 as the positive control, we determined the subcellular distribution of BRCA1 in the prostate cancer cell lines LNCaP, DU145 and PC3 by immunohistochemical staining and Western blotting analyses.

RESULTSBRCA1 was present in the prostate cancer cell lines LNCaP, DU145 and PC3. Ionizing radiation induced BRCA1 nuclear export, increasing from 14% to 40% in the cytoplasma (P < 0.01) and decreasing from 46% to 21% in the nuclei (P < 0.01). This DNA damage-induced BRCA1 nuclear export occurred only in the p53 wild-type but not in the p53 mutant cell line. The apoptosis rate of LNCaP cells was as high as 40% after nuclear export, with an obvious increase of cleaved caspase-3, which was correlated with BRCA1 nuclear-cytoplasmic shuttling.

CONCLUSIONCytoplasmic relocalization of the BRCA1 protein may be a mechanism whereby the BRCA1 function is regulated in response to DNA damage. Its induction of a higher rate of cell apoptosis indicates BRCA1 to be another good biomarker for the treatment of prostate cancer.

BRCA1 Protein ; metabolism ; Blotting, Western ; Cell Line, Tumor ; DNA Damage ; Humans ; Immunohistochemistry ; Male ; Prostatic Neoplasms ; genetics ; metabolism ; pathology ; Tumor Suppressor Protein p53 ; metabolism