English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Background   BRCA1  mutation carriers face a high lifetime risk of developing both breast and ovarian cancer. Haploinsufficiency is thought to predispose these women to cancer by reducing the pool of available BRCA1 transcript and protein, thereby compromising BRCA1 function. Whether or not cancer-free  BRCA1  mutation carriers have lower messenger (m)RNA transcript levels in peripheral blood leukocytes has not been evaluated. The primary aim of this study was to characterize an association between  BRCA1  mutation status and  BRCA1  mRNA leukocyte expression levels among healthy women with a  BRCA1  mutation.    Method  RNA was extracted from freshly isolated peripheral blood leukocytes of 58 cancer-free, female participants (22  BRCA1  mutation carriers and 36 non-carriers). The expression levels of 236 cancer-associated genes, including  BRCA1,  were quantified using the Human Cancer Reference gene panel from the Nanostring Technologies nCounter Analysis System.    Results  Multivariate modeling demonstrated that carrying a  BRCA1  mutation was the most significant predictor of  BRCA1  mRNA levels.  BRCA1  mRNA levels were significantly lower in  BRCA1  mutation carriers compared to non-carriers (146.7 counts vs. 175.1 counts;  P  = 0.002). Samples with  BRCA1  mutations within exon 11 had lower  BRCA1  mRNA levels than samples with mutations within the 5′ and 3′ regions of the  BRCA1  gene (122.1 counts vs. 138.9 and 168.6 counts, respectively;  P  = 0.003). Unsupervised hierarchical clustering of gene expression profiles from freshly isolated blood leukocytes revealed that  BRCA1  mutation carriers cluster more closely with other  BRCA1  mutation carriers than with  BRCA1  wild-type samples. Moreover, a set of 17 genes (including  BRCA1 ) previously shown to be involved in carcinogenesis, were differentially expressed between  BRCA1  mutation carriers and non-carriers.    Conclusion  Overall, these findings support the concept of  BRCA1  haploinsufficiency wherein a specific mutation results in dosage-dependent alteration of  BRCA1  at the transcriptional level. This study is the first to show a decrease in  BRCA1  mRNA expression in freshly isolated blood leukocytes from healthy, unaffected  BRCA1  mutation carriers.    Electronic supplementary material  The online version of this article (doi:10.1186/s13058-016-0739-8) contains supplementary material, which is available to authorized users.

Reduced BRCA1 transcript levels in freshly isolated blood leukocytes from BRCA1 mutation carriers is mutation specific