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An integrated genomics analysis of epigenetic subtypes in human breast tumors links DNA methylation patterns to chromatin states in normal mammary cells

Overview of attention for article published in Breast Cancer Research, February 2016
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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 (87th percentile)
  • Good Attention Score compared to outputs of the same age and source (76th percentile)

Mentioned by

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25 X users

Citations

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67 Dimensions

Readers on

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106 Mendeley
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1 CiteULike
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Title
An integrated genomics analysis of epigenetic subtypes in human breast tumors links DNA methylation patterns to chromatin states in normal mammary cells
Published in
Breast Cancer Research, February 2016
DOI 10.1186/s13058-016-0685-5
Pubmed ID
Authors

Karolina Holm, Johan Staaf, Martin Lauss, Mattias Aine, David Lindgren, Pär-Ola Bendahl, Johan Vallon-Christersson, Rosa Bjork Barkardottir, Mattias Höglund, Åke Borg, Göran Jönsson, Markus Ringnér

Abstract

Aberrant DNA methylation is frequently observed in breast cancer. However, the relationship between methylation patterns and the heterogeneity of breast cancer has not been comprehensively characterized. Whole-genome DNA methylation analysis using Illumina Infinium HumanMethylation450 BeadChip arrays was performed on 188 human breast tumors. Unsupervised bootstrap consensus clustering was performed to identify DNA methylation epigenetic subgroups (epitypes). The Cancer Genome Atlas data, including methylation profiles of 669 human breast tumors, was used for validation. The identified epitypes were characterized by integration with publicly available genome-wide data, including gene expression levels, DNA copy numbers, whole-exome sequencing data, and chromatin states. We identified seven breast cancer epitypes. One epitype was distinctly associated with basal-like tumors and with BRCA1 mutations, one epitype contained a subset of ERBB2-amplified tumors characterized by multiple additional amplifications and the most complex genomes, and one epitype displayed a methylation profile similar to normal epithelial cells. Luminal tumors were stratified into the remaining four epitypes, with differences in promoter hypermethylation, global hypomethylation, proliferative rates, and genomic instability. Specific hyper- and hypomethylation across the basal-like epitype was rare. However, we observed that the candidate genomic instability drivers BRCA1 and HORMAD1 displayed aberrant methylation linked to gene expression levels in some basal-like tumors. Hypomethylation in luminal tumors was associated with DNA repeats and subtelomeric regions. We observed two dominant patterns of aberrant methylation in breast cancer. One pattern, constitutively methylated in both basal-like and luminal breast cancer, was linked to genes with promoters in a Polycomb-repressed state in normal epithelial cells and displayed no correlation with gene expression levels. The second pattern correlated with gene expression levels and was associated with methylation in luminal tumors and genes with active promoters in normal epithelial cells. Our results suggest that hypermethylation patterns across basal-like breast cancer may have limited influence on tumor progression and instead reflect the repressed chromatin state of the tissue of origin. On the contrary, hypermethylation patterns specific to luminal breast cancer influence gene expression, may contribute to tumor progression, and may present an actionable epigenetic alteration in a subset of luminal breast cancers.

X Demographics

X Demographics

The data shown below were collected from the profiles of 25 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 106 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Netherlands 1 <1%
Sweden 1 <1%
Norway 1 <1%
Canada 1 <1%
Unknown 102 96%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 23 22%
Researcher 19 18%
Student > Master 10 9%
Student > Doctoral Student 8 8%
Student > Bachelor 8 8%
Other 15 14%
Unknown 23 22%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 28 26%
Agricultural and Biological Sciences 20 19%
Medicine and Dentistry 13 12%
Engineering 3 3%
Computer Science 2 2%
Other 10 9%
Unknown 30 28%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 14. 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 15 March 2016.
All research outputs
#2,551,593
of 25,373,627 outputs
Outputs from Breast Cancer Research
#251
of 2,052 outputs
Outputs of similar age
#39,397
of 312,035 outputs
Outputs of similar age from Breast Cancer Research
#8
of 34 outputs
Altmetric has tracked 25,373,627 research outputs across all sources so far. Compared to these this one has done well and is in the 89th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 2,052 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 12.2. This one has done well, scoring higher than 87% 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 312,035 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 87% of its contemporaries.
We're also able to compare this research output to 34 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 76% of its contemporaries.