Browsing by Subject "BRCA1"

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    LncRNA AY343892 inhibits breast cancer development by positively regulating BRCA1-mediated transcription of PTEN
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Li, Yan; Zhang, Miao; Li, Fan
    reast cancer remains a major challenge despite dramatic advances in cancer research. The long non-coding RNA (lncRNA) has been reported to associate with carcinogenesis and progression of various cancers. In this research, we found that lncRNA AY343892 was significantly down-regulated in breast cancer tissues and cells. Besides, breast cancer patients with high AY343892 level exhibited a favorable prognosis. Functional assays indicated that overexpression of AY343892 significantly inhibited proliferation and promoted apoptosis in breast cancer cells. In terms of mechanism, PTEN and BRCA1 were confirmed to be regulated by AY343892 in breast cancer. Luciferase activity and chromatin immunoprecipitation (ChIP) assays indicated that AY343892 can regulate the promoter of PTEN by binding to BCRA1. Further investigation suggested that knockdown of AY343892 significantly promoted MDA-MB-231 cell proliferation and inhibited MDA-MB-231 cell apoptosis. However, these effects were reversed when PTEN was up- regulated. Moreover, PTEN silence can also countervail the inhibitory effect of overexpressed BCRA1 or AY343892 on the expressions of genes related to proliferation and apoptosis in breast cancer. In conclusion, this study illustrated that AY343892 inhibited breast cancer development by positively regulating BRCA1-mediated transcription of PTEN. This finding contributes to a better understanding in the pathogenesis of breast cancer and provides a theoretical basis for the treatment of breast cancer patients
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    Molecular characterization and clinical interpretation of BRCA1/BRCA2 variants in families from Murcia (south-eastern Spain) with hereditary breast and ovarian cancer: clinical–pathological features in BRCA carriers and non-carriers
    (Springer, 2017-05-05) Gabaldó Barrios, Xavier; Marín Vera, Miguel; Sánchez Bermúdez, Ana Isabel; Macías Cerrolaza, José Antonio; Sánchez Henarejos, Pilar; Zafra Poves, Marta; García Hernández, María Rosario; Cuevas Tortosa, Encarna; Aliaga Baño, Ángeles; Castillo Guardiola, Verónica; Martínez Hernández, Pedro; Tovar Zapata, Isabel; Martínez Barba, Enrique; Ayala de la Peña, Francisco; Alonso-Romero, José Luis; Noguera Velasco, José Antonio; Ruiz Espejo, Francisco; Sarabia Meseguer, María Desamparados; Medicina
    This is the first study performed in Murcia (south-eastern Spain) in which 592 families with hereditary breast and ovarian cancer were identified thanks to Genetic Counselling Units from this area over 6 years. Diagnostic performance was 18.1% and 194 different genetic variants were obtained. Variants with uncertain significance accounted for only 5.6% of the total number of reports, so our population has been well characterised. In BRCA1 gene, two novel variants were found (c.1859delT and c.3205C > T) and the most frequently detected mutations were c.68_69delAG, c.212 + 1G > A, c.5123C > A, c.211A > G and c.1918C > T, which together represented 56.67% of total pathogenic mutations. In BRCA2 gene, four recurrent variants were described (deletion of entire exon 2, c.9117G > A, c.3264dupT and c.3455T > G) representing 43.5% of the mutations in this gene. Mutation c.68_69delAG and deletion of entire exon 2 in BRCA1 and BRCA2 genes respectively were the most prevalent variants in our population. Regarding the genotype-phenotype relation, mutation c.212 + 1G > A appeared in an important percentage of breast and ovarian cancer cases, c.5123C > A in bilateral breast cancer and c.9117G > A in bilateral breast cancer and ovarian cancer. With respect to clinical–pathological characteristic, BRCA1/BRCA2 mutation carriers showed earlier onset age of breast tumour and higher risk of developing contra lateral breast cancer than non-informative cases. Moreover, association between either molecular subtype triple negative breast cancer or ovarian cancer and BRCA1 carriers was obtained.
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    Novel BRCA1 deleterious mutation (c.1918C>T) in familial breast and ovarian cancer syndrome who share a common ancestry
    (Springer, 2014-03-16) Gabaldó Barrios, Xavier; Alonso-Romero, José Luis; Marín Vera, Miguel; Marín Zafra, Gema; Sánchez Henarejos, Pilar; Sánchez Bermúdez, Ana Isabel; Ruiz Espejo, Francisco; Sarabia Meseguer, María Desamparados; Medicina
    Mutations in breast cancer susceptibility (BRCA) genes lead to defects in DNA repair processes resulting in elevated genome instability and predisposing to breast and ovarian cancer. We report a novel mutation (c.1918C>T) in the exon 11 of the BRCA1 gene that consists of a nonsense mutation that causes a stop codon downstream in the 640 position of the protein. The mutation was present in two Spanish unrelated families and was associated with four breast cancer cases, including two bilateral breast cancer (one of them synchronous). The median age/mean age (range) was 48.5/44.25 years (27–53). This finding led us to perform haplotype analysis in all family carriers. Four highly polymorphic microsatellite markers were used (17-3858, 17-3930, D17S855, D17S1326) to establish whether or not all these families had a common ancestor. This analysis showed that all mutation carriers of these families had a common haplotype. None of the noncarriers of the mutation or of the 24 healthy controls showed this haplotype. Therefore, the c.1918C>T mutation carriers from these two families allows us to assert that all analyzed mutation carriers share a common ancestry.