↓ Skip to main content

Genome‐wide DNA methylation patterns in pancreatic ductal adenocarcinoma reveal epigenetic deregulation of SLIT‐ROBO, ITGA2 and MET signaling

Overview of attention for article published in International Journal of Cancer, May 2014
Altmetric Badge

About this Attention Score

  • Good Attention Score compared to outputs of the same age (74th percentile)
  • Good Attention Score compared to outputs of the same age and source (66th percentile)

Mentioned by

twitter
3 X users
patent
1 patent

Citations

dimensions_citation
187 Dimensions

Readers on

mendeley
152 Mendeley
You are seeing a free-to-access but limited selection of the activity Altmetric has collected about this research output. Click here to find out more.
Title
Genome‐wide DNA methylation patterns in pancreatic ductal adenocarcinoma reveal epigenetic deregulation of SLIT‐ROBO, ITGA2 and MET signaling
Published in
International Journal of Cancer, May 2014
DOI 10.1002/ijc.28765
Pubmed ID
Authors

Katia Nones, Nic Waddell, Sarah Song, Ann‐Marie Patch, David Miller, Amber Johns, Jianmin Wu, Karin S. Kassahn, David Wood, Peter Bailey, Lynn Fink, Suzanne Manning, Angelika N. Christ, Craig Nourse, Stephen Kazakoff, Darrin Taylor, Conrad Leonard, David K. Chang, Marc D. Jones, Michelle Thomas, Clare Watson, Mark Pinese, Mark Cowley, Ilse Rooman, Marina Pajic, APGI, Giovanni Butturini, Anna Malpaga, Vincenzo Corbo, Stefano Crippa, Massimo Falconi, Giuseppe Zamboni, Paola Castelli, Rita T. Lawlor, Anthony J. Gill, Aldo Scarpa, John V. Pearson, Andrew V. Biankin, Sean M. Grimmond

Abstract

The importance of epigenetic modifications such as DNA methylation in tumorigenesis is increasingly being appreciated. To define the genome-wide pattern of DNA methylation in pancreatic ductal adenocarcinomas (PDAC), we captured the methylation profiles of 167 untreated resected PDACs and compared them to a panel of 29 adjacent nontransformed pancreata using high-density arrays. A total of 11,634 CpG sites associated with 3,522 genes were significantly differentially methylated (DM) in PDAC and were capable of segregating PDAC from non-malignant pancreas, regardless of tumor cellularity. As expected, PDAC hypermethylation was most prevalent in the 5' region of genes (including the proximal promoter, 5'UTR and CpG islands). Approximately 33% DM genes showed significant inverse correlation with mRNA expression levels. Pathway analysis revealed an enrichment of aberrantly methylated genes involved in key molecular mechanisms important to PDAC: TGF-β, WNT, integrin signaling, cell adhesion, stellate cell activation and axon guidance. Given the recent discovery that SLIT-ROBO mutations play a clinically important role in PDAC, the role of epigenetic perturbation of axon guidance was pursued in more detail. Bisulfite amplicon deep sequencing and qRT-PCR expression analyses confirmed recurrent perturbation of axon guidance pathway genes SLIT2, SLIT3, ROBO1, ROBO3, ITGA2 and MET and suggests epigenetic suppression of SLIT-ROBO signaling and up-regulation of MET and ITGA2 expression. Hypomethylation of MET and ITGA2 correlated with high gene expression, which was associated with poor survival. These data suggest that aberrant methylation plays an important role in pancreatic carcinogenesis affecting core signaling pathways with potential implications for the disease pathophysiology and therapy.

X Demographics

X Demographics

The data shown below were collected from the profiles of 3 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 152 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 <1%
Denmark 1 <1%
Belgium 1 <1%
Australia 1 <1%
Unknown 148 97%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 30 20%
Researcher 23 15%
Student > Master 20 13%
Student > Bachelor 12 8%
Student > Doctoral Student 8 5%
Other 25 16%
Unknown 34 22%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 44 29%
Medicine and Dentistry 29 19%
Agricultural and Biological Sciences 27 18%
Engineering 3 2%
Chemistry 2 1%
Other 9 6%
Unknown 38 25%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 5. 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 31 August 2021.
All research outputs
#6,601,941
of 24,571,708 outputs
Outputs from International Journal of Cancer
#4,191
of 12,088 outputs
Outputs of similar age
#59,093
of 232,228 outputs
Outputs of similar age from International Journal of Cancer
#43
of 130 outputs
Altmetric has tracked 24,571,708 research outputs across all sources so far. This one has received more attention than most of these and is in the 72nd percentile.
So far Altmetric has tracked 12,088 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.8. This one has gotten more attention than average, scoring higher than 65% 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 232,228 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 74% of its contemporaries.
We're also able to compare this research output to 130 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 66% of its contemporaries.