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Identification of genes epigenetically silenced by CpG methylation in human gastric carcinoma

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dc.contributor.authorDo Jee, Chang-
dc.contributor.authorKim, Min A.-
dc.contributor.authorJung, Eun Ji-
dc.contributor.authorKim, Jin-
dc.contributor.authorKim, Woo Ho-
dc.date.accessioned2012-05-31T01:14:45Z-
dc.date.available2012-05-31T01:14:45Z-
dc.date.issued2009-05-
dc.identifier.citationEUROPEAN JOURNAL OF CANCER; Vol.45 7; 1282-1293ko_KR
dc.identifier.issn0959-8049-
dc.identifier.urihttps://hdl.handle.net/10371/76643-
dc.description.abstractTo identify novel methylation-silenced genes in gastric cancer, we carried out a genome-wide search for genes that are up-regulated after treatment with the demethylating agent, 5-aza-2`-deoxycytidine (5Aza-dC). When three gastric cancer cell lines (SNU-1,-601, and -719) were treated with 5Aza-dC, 143 genes were found to be upregulated by twofold or more using oligonucleotide microarrays. Six of these genes, i.e. TFP12, GPX3, GPX1, IGFBP6, IRF7 and DMRT1, showed promoter hypermethylation in one or more gastric cancer cell lines, but were unmethylated in normal gastric mucosa by bisulphite sequencing and methylation-specific PCR analysis. The following percentages of these genes were found to be aberrantly methylated in gastric cancer samples; TFP12 (80.9%), GPX3 (30.1%), DMRT1 (46.9%), GPX1 (16.7%), IGFBP6 (22.6%) and IRF7 (32.1%). Interestingly, the survival of patients possessing methylated alleles of TFPI2 (123/152, 80.9%) was poorer than that of patients with unmethylated alleles (p = 0.023). Multivariate analysis confirmed that TFPI2 methylation is a significant and independent prognostic factor in gastric carcinoma. Furthermore, altered TFP12 expression, as demonstrated by immunohistochemistry in 566 consecutive gastric cancer tissues, was found to be significantly associated with sex (p = 0.003), WHO classification (p < 0.001), and a mixed subtype by Lauren`s classification (p < 0.001). Thus, the present study identified several novel genes, which were methylated in gastric cancer and among them, methylation of TFPI2 was an unfavourable prognostic marker. (c) 2008 Elsevier Ltd. All rights reserved.ko_KR
dc.language.isoenko_KR
dc.publisherELSEVIER SCI LTDko_KR
dc.subjectDNA methylationko_KR
dc.subjectStomach neoplasmsko_KR
dc.subjectSurvival analysisko_KR
dc.subjectImmunohistochemistryko_KR
dc.subjectOligonucleotide array sequenceko_KR
dc.subjectanalysisko_KR
dc.titleIdentification of genes epigenetically silenced by CpG methylation in human gastric carcinomako_KR
dc.typeArticleko_KR
dc.contributor.AlternativeAuthor도지창-
dc.contributor.AlternativeAuthor김민아-
dc.contributor.AlternativeAuthor정은지-
dc.contributor.AlternativeAuthor김진-
dc.contributor.AlternativeAuthor김우호-
dc.identifier.doi10.1016/j.ejca.2008.12.027-
dc.citation.journaltitleEUROPEAN JOURNAL OF CANCER-
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