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

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

1
Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, 7936 One Medical Center Drive, Lebanon, NH 03756, USA
2
Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Yogesh Kumar Vashist
Received: 3 January 2017 / Revised: 14 February 2017 / Accepted: 22 February 2017 / Published: 2 March 2017
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
View Full-Text   |   Download PDF [2797 KB, uploaded 3 March 2017]   |  

Abstract

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. View Full-Text
Keywords: serrated polyp; methylation; sessile serrated adenoma; colon cancer serrated polyp; methylation; sessile serrated adenoma; colon cancer
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Andrew, A.S.; Baron, J.A.; Butterly, L.F.; Suriawinata, A.A.; Tsongalis, G.J.; Robinson, C.M.; Amos, C.I. Hyper-Methylated Loci Persisting from Sessile Serrated Polyps to Serrated Cancers. Int. J. Mol. Sci. 2017, 18, 535.

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