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DNA methylation profiles of gastric carcinoma characterized by quantitative DNA methylation analysis

Cited 125 time in Web of Science Cited 134 time in Scopus
Authors
Kang, Gyeong Hoon; Lee, Sun; Cho, Nam-Yun; Gandamihardja, Tasha; Long, Tiffany I; Weisenberger, Daniel J; Campan, Mihaela; Laird, Peter W
Issue Date
2007-12-26
Publisher
Nature Publishing Group
Citation
Lab Invest. 2008 Feb;88(2):161-70. Epub 2007 Dec 24.
Keywords
AdultAgedAged, 80 and overCarcinoma/*metabolism/microbiology/pathologyCpG Islands*DNA MethylationFemaleGastric Mucosa/metabolism/microbiologyGastritis/*metabolism/microbiology/pathologyHelicobacter pylori/isolation & purificationHerpesvirus 4, Human/isolation & purificationHumansMaleMicrosatellite InstabilityMiddle AgedRNA, Messenger/metabolismStomach Neoplasms/*metabolism/microbiology/pathologyTumor Markers, Biological/*metabolism
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.
ISSN
1530-0307 (Electronic)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18158559

http://hdl.handle.net/10371/29600
DOI
https://doi.org/10.1038/labinvest.3700707
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College of Medicine/School of Medicine (의과대학/대학원)Program in Cancer Biology (협동과정-종양생물학전공)Journal Papers (저널논문_협동과정-종양생물학전공)
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