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Coordinated epigenetic remodelling of transcriptional networks occurs during early breast carcinogenesis

Overview of attention for article published in Clinical Epigenetics, May 2015
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (81st percentile)

Mentioned by

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9 tweeters
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1 Facebook page
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1 Wikipedia page

Citations

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22 Dimensions

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51 Mendeley
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Title
Coordinated epigenetic remodelling of transcriptional networks occurs during early breast carcinogenesis
Published in
Clinical Epigenetics, May 2015
DOI 10.1186/s13148-015-0086-0
Pubmed ID
Authors

Warwick J Locke, Elena Zotenko, Clare Stirzaker, Mark D Robinson, Rebecca A Hinshelwood, Andrew Stone, Roger R Reddel, Lily I Huschtscha, Susan J Clark

Abstract

Dysregulation of the epigenome is a common event in malignancy; however, deciphering the earliest cancer-associated epigenetic events remains a challenge. Cancer epigenome studies to date have primarily utilised cancer cell lines or clinical samples, where it is difficult to identify the initial epigenetic lesions from those that occur over time. Here, we analysed the epigenome of human mammary epithelial cells (HMEC) and a matched variant cell population (vHMEC) that have spontaneously escaped senescence and undergone partial carcinogenic transformation. Using this model of basal-like breast carcinogenesis, we provide striking new insights into the very first epigenetic changes that occur during the initial stages of malignancy. The first phase of malignancy is defined by coordinated changes in the epigenome. At the chromatin level, this is embodied in long-range epigenetic deregulation, which involves the concomitant but atypical acquisition or loss of active and repressive histone modifications across large regional blocks. Changes in DNA methylation also occurs in a highly coordinated manner. We identified differentially methylated regions (DMRs) in the very earliest passages of vHMECs. Notably, we find that differential methylation targets loci regulated by key transcription factors including p53, AHR and E2F family members suggesting that epigenetic deregulation of transcription factor binding is a key event in breast carcinogenesis. Interestingly, DMRs identified in vHMEC are extensively methylated in breast cancer, with hypermethylation frequently encroaching into neighbouring regions. A subset of vHMEC DMRs exhibited a strong basal-like cancer specific hypermethylation. Here, we generated epigenome-wide maps of the earliest phase of breast malignancy and show long-range epigenetic deregulation and coordinated DNA hypermethylation targets loci regulated by key transcription factors. These findings support a model where induction of breast cancer occurs through epigenetic disruption of transcription factor binding leading to deregulation of cancer-associated transcriptional networks. With their stability and very early occurrence, vHMECs hypermethylated loci could serve as excellent biomarkers for the initial detection of basal breast cancer.

Twitter Demographics

The data shown below were collected from the profiles of 9 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 51 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 2%
Italy 1 2%
Brazil 1 2%
Unknown 48 94%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 15 29%
Researcher 9 18%
Student > Doctoral Student 5 10%
Professor > Associate Professor 4 8%
Student > Master 4 8%
Other 8 16%
Unknown 6 12%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 21 41%
Agricultural and Biological Sciences 11 22%
Medicine and Dentistry 5 10%
Mathematics 1 2%
Environmental Science 1 2%
Other 2 4%
Unknown 10 20%

Attention Score in Context

This research output has an Altmetric Attention Score of 8. 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 08 April 2019.
All research outputs
#2,986,360
of 18,119,184 outputs
Outputs from Clinical Epigenetics
#191
of 1,000 outputs
Outputs of similar age
#43,146
of 236,839 outputs
Outputs of similar age from Clinical Epigenetics
#1
of 1 outputs
Altmetric has tracked 18,119,184 research outputs across all sources so far. Compared to these this one has done well and is in the 83rd percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,000 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.1. This one has done well, scoring higher than 80% of its peers.
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 236,839 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 81% of its contemporaries.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them