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

Overview of attention for article published in Breast Cancer Research, January 2016
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Title
Reduced BRCA1 transcript levels in freshly isolated blood leukocytes from BRCA1 mutation carriers is mutation specific
Published in
Breast Cancer Research, January 2016
DOI 10.1186/s13058-016-0739-8
Pubmed ID
Authors

Chehade, Rania, Pettapiece-Phillips, Rachael, Salmena, Leonardo, Kotlyar, Max, Jurisica, Igor, Narod, Steven A, Akbari, Mohammad R, Kotsopoulos, Joanne, Rania Chehade, Rachael Pettapiece-Phillips, Leonardo Salmena, Max Kotlyar, Igor Jurisica, Steven A. Narod, Mohammad R. Akbari, Joanne Kotsopoulos

Abstract

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. 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. 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. 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.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 37 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Belgium 1 3%
Unknown 36 97%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 6 16%
Student > Doctoral Student 5 14%
Student > Bachelor 3 8%
Professor > Associate Professor 3 8%
Student > Master 3 8%
Other 6 16%
Unknown 11 30%
Readers by discipline Count As %
Agricultural and Biological Sciences 8 22%
Biochemistry, Genetics and Molecular Biology 6 16%
Medicine and Dentistry 4 11%
Unspecified 1 3%
Nursing and Health Professions 1 3%
Other 4 11%
Unknown 13 35%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 14 September 2016.
All research outputs
#6,360,047
of 8,380,241 outputs
Outputs from Breast Cancer Research
#810
of 1,046 outputs
Outputs of similar age
#180,502
of 255,166 outputs
Outputs of similar age from Breast Cancer Research
#24
of 28 outputs
Altmetric has tracked 8,380,241 research outputs across all sources so far. This one is in the 13th percentile – i.e., 13% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,046 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.1. This one is in the 11th percentile – i.e., 11% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 255,166 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 16th percentile – i.e., 16% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 28 others from the same source and published within six weeks on either side of this one. This one is in the 3rd percentile – i.e., 3% of its contemporaries scored the same or lower than it.