Hyper-Methylated Loci Persisting from Sessile Serrated Polyps to Serrated Cancers

Int J Mol Sci. 2017 Mar 2;18(3):535. doi: 10.3390/ijms18030535.


Although serrated polyps were historically considered to pose little risk, it is now understood that progression down the serrated pathway could account for as many as 15%-35% of colorectal cancers. The sessile serrated adenoma/polyp (SSA/P) is the most prevalent pre-invasive serrated lesion. Our objective was to identify the CpG loci that are persistently hyper-methylated during serrated carcinogenesis, from the early SSA/P lesion through the later cancer phases of neoplasia development. We queried the loci hyper-methylated in serrated cancers within our rightsided SSA/Ps from the New Hampshire Colonoscopy Registry, using the Illumina Infinium Human Methylation 450 k panel to comprehensively assess the DNA methylation status. We identified CpG loci and regions consistently hyper-methylated throughout the serrated carcinogenesis spectrum, in both our SSA/P specimens and in serrated cancers. Hyper-methylated CpG loci included the known the tumor suppressor gene RET (p = 5.72 x 10-10), as well as loci in differentially methylated regions for GSG1L, MIR4493, NTNG1, MCIDAS, ZNF568, and RERG. The hyper-methylated loci that we identified help characterize the biology of SSA/P development, and could be useful as therapeutic targets, or for future identification of patients who may benefit from shorter surveillance intervals.

Keywords: colon cancer; methylation; serrated polyp; sessile serrated adenoma.

MeSH terms

  • Adenoma / genetics*
  • Colonic Polyps / genetics*
  • Colorectal Neoplasms / genetics*
  • CpG Islands
  • DNA Methylation*
  • Early Detection of Cancer
  • Female
  • Genetic Loci
  • Humans
  • Male
  • Middle Aged