Breast cancer risk associated with BRCA1 and BRCA2 in diverse populations

Fackenthal, James D.; Olopade, Olufunmilayo I.

doi:10.1038/nrc2054

Cited by 413 publications

(324 citation statements)

References 156 publications

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“…It is therefore possible that the lack of Top1 degradation in cancer cells 34 could be related to Brca1-inactivating mutations that occur frequently during tumorigenesis. 49 Other parallel pathways besides Brca1 probably also contribute to Top1 degradation as Brca1 −/− cells are not completely defective in Top1 degradation (Fig. 5d, top panel).…”

Section: Discussionmentioning

confidence: 99%

Hyperphosphorylation of RNA Polymerase II in Response to Topoisomerase I Cleavage Complexes and Its Association with Transcription- and BRCA1-dependent Degradation of Topoisomerase I

Sordet

Larochelle

Nicolas

et al. 2008

Journal of Molecular Biology

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SUMMARYThe progression of RNA polymerase II can be blocked by lesions on the DNA template. In this study, we focused in the modifications of the largest subunit of RNA polymerase II, Rpb1, in response to stabilized topoisomerase I (Top1)-DNA cleavage complexes. In addition to DNA modifications (base damages and strand breaks), Top1 cleavage complexes can be trapped by camptothecin and its derivatives used in cancer treatment. We find that, within a few minutes, camptothecin produces the complete hyperphosphorylation of Rpb1 in both primary and transformed cancer cells. Hyperphosphorylation is rapidly reversible following camptothecin removal. Hyperphosphorylation occurs selectively on the serine-5 residue of the conserved heptapeptide repeats in the Rpb1-carboxyterminal domain and is mediated principally by the TFIIH-associated kinase, Cdk7. Hyperphosphorylated Rpb1 is not primarily targeted for proteosomal degradation, but instead is subjected to cycles of phosphorylation and dephosphorylation as long as Top1 cleavage complexes are trapped by camptothecin. Finally, we show that transcription-induced degradation of Top1 is Brca1-dependent, suggesting a role for Brca1 in the repair or removal of transcription-blocking Top1-DNA cleavage complexes.

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Section: Discussionmentioning

confidence: 99%

Hyperphosphorylation of RNA Polymerase II in Response to Topoisomerase I Cleavage Complexes and Its Association with Transcription- and BRCA1-dependent Degradation of Topoisomerase I

Sordet

Larochelle

Nicolas

et al. 2008

Journal of Molecular Biology

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“…96 On the other hand, the BRCA1/2 gene is a well-characterized cancer susceptibility gene that is associated with hereditary breast and ovarian cancer. 97,98 Shen et al 99 suggested that genetic polymorphisms in the miR-146a gene might be associated with young age in familial cases of breast or ovarian cancer. The basal phenotype have a strong relationship to BRCA1 mutations, and 80-90% of BRCA1-abnomality expressing cancers exhibiting this phenotype.…”

Section: Mirna In Triple-negative Breast Cancermentioning

confidence: 99%

Recent trends in microRNA research into breast cancer with particular focus on the associations between microRNAs and intrinsic subtypes

et al. 2016

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MicroRNAs (miRNAs) are short non-coding RNAs that regulate the function of target genes at the post-transcriptional phase. miRNAs are considered to have roles in the development, progression and metastasis of cancer. Recent studies have indicated that particular miRNA signatures are correlated with tumor aggressiveness, response to drug therapy and patient outcome in breast cancer. On the other hand, in routine clinical practice, the treatment regimens for breast cancer are determined based on the intrinsic subtype of the primary tumor. Previous studies have shown that miRNA expression profiles of each intrinsic subtypes of breast cancer differ. In hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer, miRNA expressions are found to be correlated with endocrine therapy resistance, progesterone receptor expression and heat shock protein activity. Some miRNAs are associated with resistance to HER2-targeted therapy and HER3 expression in HER2-positive breast cancer. In triple-negative breast cancer, miRNA expressions are found to be associated with BRCA mutations, immune system, epithelial-mesenchymal transition, cancer stem cell properties and androgen receptor expression. As it has been clarified that the expression levels and functions of miRNA differ among the various subtypes of breast cancer, and it is necessary to take account of the characteristics of each breast cancer subtype during research into the roles of miRNA in breast cancer. In addition, the discovery of the roles played by miRNAs in breast cancer might provide new opportunities for the development of novel strategies for diagnosing and treating breast cancer.

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“…The prevalence of BRCA1 mutation carriers is around 1/800 in the general population, however, it can vary significantly among different countries or ethnic groups (28,35).…”

Section: Discussionmentioning

confidence: 99%

“…Among them, Huntington's chorea is caused by the expanded repetition of the CAG triplet localized in Exon 1 of the Huntingtin gene (also called IT15/HTT/HD). There are four categories based on the number of CAG-repetitions: healthy (\27 CAG), intermediate (27)(28)(29)(30)(31)(32)(33)(34)(35), those with reduced penetrance (35)(36)(37)(38)(39), and those of the diseased phenotype (>40 CAG) (15)(16)(17). For diagnosis, the length of genomic DNA fragments carrying the CAG-repeats are to be compared; typically this is performed after PCR amplification, sometimes following restriction enzyme digestion and ligation to adaptors (18) and the products are analyzed in a standard way by agarose or polyacrylamide gel electrophoresis (17,19,20), with capillary gel electrophoresis (17,21,22), or by sequencing.…”

mentioning

confidence: 99%

Detection of mutations by flow cytometric melting point analysis of PCR products

et al. 2011

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Exploring the possibilities offered by flow cytometric microbead analyses for the detection of genetic alterations, an assay based on the dependence of the melting point of double-stranded DNA molecules on their length has been developed, making use of PCR products carrying biotin and fluorescent moiety on their two ends. The samples of different length PCR products immobilized on streptavidine coated microbeads are heat-treated in the presence of formamide at temperatures between the melting point of the longer and that of the shorter PCR product, when the mean fluorescence intensity of the beads carrying the shorter molecules decreases as a result of denaturation, as opposed to the sample containing the longer product. The efficacy and sensitivity of the method is demonstrated in the case of the assessment of the degree of triplet expansion in Huntington's disease. Its utility for the detection of point mutations in heterozygous clinical samples is shown in the case of the BRCA1 gene. The assay is simple and may be offered for the purposes of clinical diagnostics of a number of genetic conditions. These include screening of samples for triplet expansions and SNPs predisposing for particular pathological or pharmacogenomic conditions. In general, the method described herein is offered for the diagnosis of any pathological condition where the length of a genomic or cDNA sequence is expected to be different from that of the normal allele. IN conjunction with microbead analysis, flow cytometry is a sensitive and versatile platform for the biochemical, immunological, or molecular biological analysis of proteins and nucleic acids (1-9). Extending this spectrum, the method described herein is based on the dependence of the melting temperature [T m ; the temperature where 50% of the DNA molecules is present in denatured, single-stranded (ss) form] of double-stranded (ds) DNA molecules on their length. This temperature can be reduced to near ambient conditions in the presence of H-bond destabilizing reagents such as DMSO or formamide (10,11). Above its T m , a sample containing a PCR product prepared using a pair of biotinylated and fluorescent primers and immobilized on microbeads via the biotin moiety, will dissociate into free ss DNA molecules labeled with the fluorescent tag and the bead-attached non-fluorescent, biotinylated complementary strand. The degree of denaturation, that is, ratio of the ds and ss species at equilibrium will depend on the incubation temperature relative to the T m . Since the degree of denaturation at a given temperature is expected to depend also on the length of the DNA molecule (12,13), measurement of the above ratio by flow cytometry may be used for the length comparison of PCR products prepared from DNA samples in diseases where this approach might be of diagnostic value. The range of related potential applications include genetic disorders where the underlying disease might involve insertions, deletions, triplet expansions, microsatellite polymorphisms. In addition, when prim...

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Breast cancer risk associated with BRCA1 and BRCA2 in diverse populations

Cited by 413 publications

References 156 publications

Hyperphosphorylation of RNA Polymerase II in Response to Topoisomerase I Cleavage Complexes and Its Association with Transcription- and BRCA1-dependent Degradation of Topoisomerase I

Hyperphosphorylation of RNA Polymerase II in Response to Topoisomerase I Cleavage Complexes and Its Association with Transcription- and BRCA1-dependent Degradation of Topoisomerase I

Recent trends in microRNA research into breast cancer with particular focus on the associations between microRNAs and intrinsic subtypes

Detection of mutations by flow cytometric melting point analysis of PCR products

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