Related Experiment Video

Updated: Mar 11, 2026

An Integrated Platform for Genome-wide Mapping of Chromatin States Using High-throughput ChIP-sequencing in Tumor Tissues
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Epigenetic and genetic deregulation in cancer target distinct signaling pathway domains

Yang Gao1,2, Andrew E Teschendorff3,4,5

  • 1CAS Key Lab for Computational Biology, CAS-MPG Partner Institute for Computational Biology, Chinese Academy of Sciences, Shanghai Institute for Biological Sciences, 320 Yue Yang Road, Shanghai 200031, China.

Nucleic Acids Research
|December 1, 2016
PubMed

Insights

Cancer

Area of Science:

  • Systems biology
  • Cancer epigenetics
  • Network analysis

Background:

  • Cancer involves genetic and epigenetic changes.
  • Systems-level understanding of epigenetic alterations in cancer is limited compared to genetic alterations.

Purpose of the Study:

  • To perform a pan-cancer systems-level analysis of DNA methylation (DNAm) alterations.
  • To map DNAm alterations onto the human interactome and compare their network properties with genomic alterations.
  • To identify key signaling pathways and molecular targets affected by epigenetic deregulation in cancer.

Main Methods:

  • Pan-cancer analysis of DNA methylation data.
  • Mapping candidate cancer-driver DNAm alterations onto a human protein-protein interaction network.
  • Network analysis to compare connectivity of epigenetic versus genomic alterations.
  • Meta-analysis of WNT and chemokine signaling pathways.

Main Results:

  • Functional DNAm alterations in cancer map to nodes with lower connectivity compared to genomic alterations.
  • Epigenetic alterations are enriched in extracellular and transmembrane signaling domains, unlike amplified/deleted genes (intracellular).
  • WNT and chemokine signaling pathways show preferential targeting of extracellular components by epigenetic deregulation.
  • Specific chemokine ligands/receptors linked to epigenetic enzymes identified as potential therapeutic targets.

Conclusions:

  • Epigenetic deregulation in cancer extends beyond transcription factors to modulate extracellular signaling.
  • Distinct network properties differentiate the roles of genetic and epigenetic alterations in cancer development.
  • Identified targets offer novel avenues for epigenetic therapy in cancer.

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