title: DNA methylation profiles of gastric carcinoma characterized by quantitative DNA methylation analysis.
abstract: Transcriptional silencing by CpG island hypermethylation is a potential mechanism for the inactivation of tumor-related genes. Virtually, all types of human cancers show CpG island hypermethylation, and gastric carcinoma (GC) is one of the tumors with a high frequency of aberrant CpG island hypermethylation. In this study, we prescreened DNA methylation of 170 CpG island loci in a training set of 8 paired GC and GC-associated non-neoplastic mucosae (GCN) using MethyLight technology and selected 27 DNA methylation markers showing higher methylation frequency or level in GC than in GCN. These markers were then analyzed in a tester set of 25 paired GC and GCN and 27 chronic gastritis (CG) from non-cancer patients to generate their DNA methylation profiles. We identified 17 novel methylation markers in GC, including SFRP4, SEZ6L, TWIST1, BCL2, KL, TERT, SCGB3A1, IGF2, GRIN2B, SFRP5, DLEC1, HOXA1, CYP1B1, SMAD9, MT1G, NR3C1, and HOXA10. Of the 27 selected CpG island loci, 23 were methylated in GC, GCN, and CG and the remainder four loci (DLEC1, CHFR, CYP1B1, and NR3C1) were only methylated in GC. We found that the number of methylated loci was significantly higher in GC than in GCN or CG and that Helicobacter pylori infection was strongly associated with aberrant CpG island hypermethylation in CG. Hypermethylation was more prevalent in Epstein-Barr virus (EBV)-positive GC than in EBV-negative GC and in diffuse-type GC than in intestinal-type GC. Through our large-scale screening of 170 CpG island loci, we found 17 new DNA methylation markers of GC, which may serve as useful markers that may identify a distinct subset of GC.
authors.affiliation: Department of Pathology, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea. ghkang@snu.ac.kr
authors.forename: Gyeong Hoon
authors.initials: GH
authors.lastname: Kang
authors.forename: Sun
authors.initials: S
authors.lastname: Lee
authors.forename: Nam-Yun
authors.initials: NY
authors.lastname: Cho
authors.forename: Tasha
authors.initials: T
authors.lastname: Gandamihardja
authors.forename: Tiffany I
authors.initials: TI
authors.lastname: Long
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weisenberger
authors.forename: Mihaela
authors.initials: M
authors.lastname: Campan
authors.forename: Peter W
authors.initials: PW
authors.lastname: Laird
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism / Q000382:microbiology; D005756:Gastritis / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D016480:Helicobacter pylori / Q000302:isolation & purification; D004854:Herpesvirus 4, Human / Q000302:isolation & purification; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger