Profile of aberrant CpG island methylation along the multistep pathway of gastric carcinogenesis

Gyeonghoon Kang, Sun Lee, Jung Sun Kim, Hwoon Yong Jung

Research output: Contribution to journalArticleResearchpeer-review

127 Citations (Scopus)

Abstract

To date, several reports on methylation of various genes in gastric cancer (GC) have been published. However, most of these studies focused on cancer tissues or a single gene only and gave no information about the methylation status of specific genes in the premalignant stages or about the concurrent methylation of other genes in specific lesions. We attempted to investigate methylation of multiple genes in a large sample collection of GC (n = 80), gastric adenoma (GA) (n = 79), intestinal metaplasia (IM) (n = 57), and chronic gastritis (CG) (n = 74). We determined the methylation frequency of 12 genes, including APC, COX-2, DAP-kinase, E-cadherin, GSTP1, hMLH1, MGMT, p16, p14, RASSF1A, THBS1, and TIMP3 by methylation-specific PCR. Five different classes of methylation behaviors were found: (1) genes methylated in GC only (GSTP1 and RASSF1A); (2) genes showing low methylation frequency (<12%) in CG, IM, and GA, but significantly higher methylation frequency in GC (COX-2, hMLH1, and p16); (3) a gene with low and similar methylation frequency (8.8-21.3%) in four-step lesions (MGMT); (4) genes with high and similar methylation frequency (53-85%) in four-step lesions (APC and E-cadherin); and (5) genes showing an increasing tendency with or without fluctuation of the methylation frequency along the progression (DAP-kinase, p14, THBS1, and TIMP3). The average number of methylated genes was 2.7, 3.6, 3.4, and 5.2 per 12 tested genes in CG, IM, GA, and GC, respectively. Our results suggest that tumor suppressor genes show a gene type-specific methylation profile and that aberrant CpG island methylation tends to accumulate along the pathway of multistep carcinogenesis.

Original languageEnglish
Pages (from-to)635-641
Number of pages7
JournalLaboratory Investigation
Volume83
Issue number5
DOIs
StatePublished - 1 May 2003

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CpG Islands
Methylation
Stomach
Carcinogenesis
Genes
Stomach Neoplasms
Metaplasia
Gastritis
Death-Associated Protein Kinases
Adenoma
Cadherins
APC Genes
Tumor Suppressor Genes
Gene Frequency

Cite this

Kang, Gyeonghoon ; Lee, Sun ; Kim, Jung Sun ; Jung, Hwoon Yong. / Profile of aberrant CpG island methylation along the multistep pathway of gastric carcinogenesis. In: Laboratory Investigation. 2003 ; Vol. 83, No. 5. pp. 635-641.
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abstract = "To date, several reports on methylation of various genes in gastric cancer (GC) have been published. However, most of these studies focused on cancer tissues or a single gene only and gave no information about the methylation status of specific genes in the premalignant stages or about the concurrent methylation of other genes in specific lesions. We attempted to investigate methylation of multiple genes in a large sample collection of GC (n = 80), gastric adenoma (GA) (n = 79), intestinal metaplasia (IM) (n = 57), and chronic gastritis (CG) (n = 74). We determined the methylation frequency of 12 genes, including APC, COX-2, DAP-kinase, E-cadherin, GSTP1, hMLH1, MGMT, p16, p14, RASSF1A, THBS1, and TIMP3 by methylation-specific PCR. Five different classes of methylation behaviors were found: (1) genes methylated in GC only (GSTP1 and RASSF1A); (2) genes showing low methylation frequency (<12{\%}) in CG, IM, and GA, but significantly higher methylation frequency in GC (COX-2, hMLH1, and p16); (3) a gene with low and similar methylation frequency (8.8-21.3{\%}) in four-step lesions (MGMT); (4) genes with high and similar methylation frequency (53-85{\%}) in four-step lesions (APC and E-cadherin); and (5) genes showing an increasing tendency with or without fluctuation of the methylation frequency along the progression (DAP-kinase, p14, THBS1, and TIMP3). The average number of methylated genes was 2.7, 3.6, 3.4, and 5.2 per 12 tested genes in CG, IM, GA, and GC, respectively. Our results suggest that tumor suppressor genes show a gene type-specific methylation profile and that aberrant CpG island methylation tends to accumulate along the pathway of multistep carcinogenesis.",
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Profile of aberrant CpG island methylation along the multistep pathway of gastric carcinogenesis. / Kang, Gyeonghoon; Lee, Sun; Kim, Jung Sun; Jung, Hwoon Yong.

In: Laboratory Investigation, Vol. 83, No. 5, 01.05.2003, p. 635-641.

Research output: Contribution to journalArticleResearchpeer-review

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