title: Hyper-Methylated Loci Persisting from Sessile Serrated Polyps to Serrated Cancers.
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.
authors.affiliation: Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, 7936 One Medical Center Drive, Lebanon, NH 03756, USA. Angeline.Andrew@dartmouth.edu.
authors.forename: Angeline S
authors.initials: AS
authors.lastname: Andrew
authors.affiliation: Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, 7936 One Medical Center Drive, Lebanon, NH 03756, USA. John.A.Baron@dartmouth.edu.|Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA. John.A.Baron@dartmouth.edu.
authors.forename: John A
authors.initials: JA
authors.lastname: Baron
authors.affiliation: Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, 7936 One Medical Center Drive, Lebanon, NH 03756, USA. Lynn.F.Butterly@dartmouth.edu.
authors.forename: Lynn F
authors.initials: LF
authors.lastname: Butterly
authors.affiliation: Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, 7936 One Medical Center Drive, Lebanon, NH 03756, USA. Arief.A.Suriawinata@dartmouth.edu.
authors.forename: Arief A
authors.initials: AA
authors.lastname: Suriawinata
authors.affiliation: Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, 7936 One Medical Center Drive, Lebanon, NH 03756, USA. Gregory.J.Tsongalis@hitchcock.org.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Tsongalis
authors.affiliation: Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, 7936 One Medical Center Drive, Lebanon, NH 03756, USA. Christina.M.Robinson@dartmouth.edu.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Robinson
authors.affiliation: Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, 7936 One Medical Center Drive, Lebanon, NH 03756, USA. Christopher.I.Amos@dartmouth.edu.
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Amos
mesh_terms: D000236:Adenoma / Q000235:genetics*; D003111:Colonic Polyps / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation; D055088:Early Detection of Cancer; D005260:Female; D056426:Genetic Loci; D006801:Humans; D008297:Male; D008875:Middle Aged
keywords: colon cancer; methylation; serrated polyp; sessile serrated adenoma