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Integrative DNA methylome analysis of pan-cancer biomarkers in cancer discordant monozygotic twin-pairs

Overview of attention for article published in Clinical Epigenetics, January 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 (89th percentile)
  • High Attention Score compared to outputs of the same age and source (90th percentile)

Mentioned by

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1 blog
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11 X users
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1 Facebook page

Citations

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32 Dimensions

Readers on

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101 Mendeley
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1 CiteULike
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Title
Integrative DNA methylome analysis of pan-cancer biomarkers in cancer discordant monozygotic twin-pairs
Published in
Clinical Epigenetics, January 2016
DOI 10.1186/s13148-016-0172-y
Pubmed ID
Authors

Leonie Roos, Jenny van Dongen, Christopher G. Bell, Andrea Burri, Panos Deloukas, Dorret I. Boomsma, Tim D. Spector, Jordana T. Bell

Abstract

A key focus in cancer research is the discovery of biomarkers that accurately diagnose early lesions in non-invasive tissues. Several studies have identified malignancy-associated DNA methylation changes in blood, yet no general cancer biomarker has been identified to date. Here, we explore the potential of blood DNA methylation as a biomarker of pan-cancer (cancer of multiple different origins) in 41 female cancer discordant monozygotic (MZ) twin-pairs sampled before or after diagnosis using the Illumina HumanMethylation450 BeadChip. We analysed epigenome-wide DNA methylation profiles in 41 cancer discordant MZ twin-pairs with affected individuals diagnosed with tumours at different single primary sites: the breast, cervix, colon, endometrium, thyroid gland, skin (melanoma), ovary, and pancreas. No significant global differences in whole blood DNA methylation profiles were observed. Epigenome-wide analyses identified one novel pan-cancer differentially methylated position at false discovery rate (FDR) threshold of 10 % (cg02444695, P = 1.8 × 10(-7)) in an intergenic region 70 kb upstream of the SASH1 tumour suppressor gene, and three suggestive signals in COL11A2, AXL, and LINC00340. Replication of the four top-ranked signals in an independent sample of nine cancer-discordant MZ twin-pairs showed a similar direction of association at COL11A2, AXL, and LINC00340, and significantly greater methylation discordance at AXL compared to 480 healthy concordant MZ twin-pairs. The effects at cg02444695 (near SASH1), COL11A2, and LINC00340 were the most promising in biomarker potential because the DNA methylation differences were found to pre-exist in samples obtained prior to diagnosis and were limited to a 5-year period before diagnosis. Gene expression follow-up at the top-ranked signals in 283 healthy individuals showed correlation between blood methylation and gene expression in lymphoblastoid cell lines at PRL, and in the skin tissue at AXL. A significant enrichment of differential DNA methylation was observed in enhancer regions (P = 0.03). We identified DNA methylation signatures in blood associated with pan-cancer, at or near SASH1, COL11A2, AXL, and LINC00340. Three of these signals were present up to 5 years prior to cancer diagnosis, highlighting the potential clinical utility of whole blood DNA methylation analysis in cancer surveillance.

X Demographics

X Demographics

The data shown below were collected from the profiles of 11 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 101 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Spain 1 <1%
Brazil 1 <1%
Unknown 99 98%

Demographic breakdown

Readers by professional status Count As %
Researcher 20 20%
Student > Ph. D. Student 18 18%
Student > Bachelor 12 12%
Student > Master 11 11%
Other 5 5%
Other 13 13%
Unknown 22 22%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 27 27%
Medicine and Dentistry 21 21%
Agricultural and Biological Sciences 13 13%
Computer Science 5 5%
Pharmacology, Toxicology and Pharmaceutical Science 4 4%
Other 5 5%
Unknown 26 26%
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 01 March 2016.
All research outputs
#2,348,600
of 23,577,761 outputs
Outputs from Clinical Epigenetics
#143
of 1,309 outputs
Outputs of similar age
#42,466
of 398,177 outputs
Outputs of similar age from Clinical Epigenetics
#5
of 53 outputs
Altmetric has tracked 23,577,761 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 90th percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,309 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.2. This one has done well, scoring higher than 89% 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 398,177 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 89% of its contemporaries.
We're also able to compare this research output to 53 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 90% of its contemporaries.