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Genome-wide methylation sequencing of paired primary and metastatic cell lines identifies common DNA methylation changes and a role for EBF3 as a candidate epigenetic driver of melanoma metastasis

Overview of attention for article published in Oncotarget, December 2016
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  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (97th percentile)
  • High Attention Score compared to outputs of the same age and source (98th percentile)

Mentioned by

news
10 news outlets
twitter
10 tweeters

Citations

dimensions_citation
48 Dimensions

Readers on

mendeley
55 Mendeley
Title
Genome-wide methylation sequencing of paired primary and metastatic cell lines identifies common DNA methylation changes and a role for EBF3 as a candidate epigenetic driver of melanoma metastasis
Published in
Oncotarget, December 2016
DOI 10.18632/oncotarget.14042
Pubmed ID
Authors

Aniruddha Chatterjee, Peter A Stockwell, Antonio Ahn, Euan J Rodger, Anna L Leichter, Michael R Eccles

Abstract

Epigenetic alterations are increasingly implicated in metastasis, whereas very few genetic mutations have been identified as authentic drivers of cancer metastasis. Yet, to date, few studies have identified metastasis-related epigenetic drivers, in part because a framework for identifying driver epigenetic changes in metastasis has not been established. Using reduced representation bisulfite sequencing (RRBS), we mapped genome-wide DNA methylation patterns in three cutaneous primary and metastatic melanoma cell line pairs to identify metastasis-related epigenetic drivers. Globally, metastatic melanoma cell lines were hypomethylated compared to the matched primary melanoma cell lines. Using whole genome RRBS we identified 75 shared (10 hyper- and 65 hypomethylated) differentially methylated fragments (DMFs), which were associated with 68 genes showing significant methylation differences. One gene, Early B Cell Factor 3 (EBF3), exhibited promoter hypermethylation in metastatic cell lines, and was validated with bisulfite sequencing and in two publicly available independent melanoma cohorts (n = 40 and 458 melanomas, respectively). We found that hypermethylation of the EBF3 promoter was associated with increased EBF3 mRNA levels in metastatic melanomas and subsequent inhibition of DNA methylation reduced EBF3 expression. RNAi-mediated knockdown of EBF3 mRNA levels decreased proliferation, migration and invasion in primary and metastatic melanoma cell lines. Overall, we have identified numerous epigenetic changes characterising metastatic melanoma cell lines, including EBF3-induced aggressive phenotypic behaviour with elevated EBF3 expression in metastatic melanoma, suggesting that EBF3 promoter hypermethylation may be a candidate epigenetic driver of metastasis.

Twitter Demographics

The data shown below were collected from the profiles of 10 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 55 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Portugal 1 2%
Unknown 54 98%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 19 35%
Researcher 10 18%
Student > Bachelor 6 11%
Student > Doctoral Student 4 7%
Student > Master 4 7%
Other 5 9%
Unknown 7 13%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 24 44%
Agricultural and Biological Sciences 11 20%
Medicine and Dentistry 5 9%
Computer Science 2 4%
Immunology and Microbiology 2 4%
Other 2 4%
Unknown 9 16%

Attention Score in Context

This research output has an Altmetric Attention Score of 81. 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 25 January 2017.
All research outputs
#290,674
of 16,530,799 outputs
Outputs from Oncotarget
#98
of 12,971 outputs
Outputs of similar age
#10,400
of 389,883 outputs
Outputs of similar age from Oncotarget
#13
of 727 outputs
Altmetric has tracked 16,530,799 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 98th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 12,971 research outputs from this source. They receive a mean Attention Score of 4.2. This one has done particularly well, scoring higher than 99% 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 389,883 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 97% of its contemporaries.
We're also able to compare this research output to 727 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 98% of its contemporaries.