Filtrating colorectal cancer associated genes by integrated analyses of global DNA methylation and hydroxymethylation in cancer and normal tissue

Sci Rep. 2016 Aug 22:6:31826. doi: 10.1038/srep31826.

Abstract

Recently, 5-hydroxymethylcytosine patterning across the tumor genome was considered as a hallmark of cancer development and progression. However, locus-specific difference of hydroxymethylation between colorectal cancer and normal tissue is unknown. In this study, we performed a newly developed method, HMST-seq, to profile 726 aberrant methylated loci and 689 aberrant hydroxymethylated loci synchronously in genome wide of colorectal cancers, majority of which presented higher methylation or lower hydroxymethylationin than in normal group. Besides, abnormal hydroxymethylated modification was more frequently occur at proximal regions close to TSSs and TSSs regions than abnormal methylation. Subsequently, we screened four genes (ALOX15, GHRHR, TFPI2 and TKTL1) with aberrant methylation and aberrant hydroxymethylation at some genome position by functional enrichment analysis as candidate genes associated with colorectal cancer. Our results may allow us to select differentially epigenetically modified target genes implicated in colorectal cancer tumorigenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5-Methylcytosine / analogs & derivatives*
  • 5-Methylcytosine / chemistry
  • Arachidonate 15-Lipoxygenase / genetics
  • Colorectal Neoplasms / genetics*
  • DNA Methylation*
  • Epigenesis, Genetic
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks*
  • Glycoproteins / genetics
  • Humans
  • Sequence Analysis, DNA
  • Transketolase / genetics

Substances

  • Glycoproteins
  • tissue-factor-pathway inhibitor 2
  • 5-hydroxymethylcytosine
  • 5-Methylcytosine
  • ALOX15 protein, human
  • Arachidonate 15-Lipoxygenase
  • TKTL1 protein, human
  • Transketolase