Profile of Aberrant CpG Island Methylation along Multistep Gastric Carcinogenesis
The stomach is one of the organs whose epithelial cells frequently undergo aberrant methylation of CpG islands. To date, several reports on the methylation of various genes in gastric cancer (GC) have been published. However, most of these studies have focused on cancer tissues or a single gene only...
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| description | The stomach is one of the organs whose epithelial cells frequently undergo aberrant methylation of CpG islands. To date, several reports on the methylation of various genes in gastric cancer (GC) have been published. However, most of these studies have 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 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: (a) genes methylated in GC only (GSTP1 and RASSF1A), (b) genes showing low methylation frequency ( |
| doi_str_mv | 10.1097/01.LAB.0000064704.53132.65 |
| format | Article |
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To date, several reports on the methylation of various genes in gastric cancer (GC) have been published. However, most of these studies have 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 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: (a) genes methylated in GC only (GSTP1 and RASSF1A), (b) genes showing low methylation frequency (<12%) in CG, IM, and gastric adenoma (GA) but significantly higher methylation frequency in GC (COX-2, hMLH1, p16), (c) a gene with low and similar methylation frequency (8.8–21.3%) in four-step lesions (MGMT), (d) genes with high and similar methylation frequency (53–85%) in four-step lesions (APC and E-cadherin), and (e) genes showing an increasing tendency with or without fluctuation of the methylation frequency along the progression (DAP-kinase, p14, THBS1, and TIMP-3). 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. Aberrant methylation at multiple loci in the same lesions suggests an overall deregulation of the methylation control, which occurs early in multistep gastric carcinogenesis. Our results suggest that tumor-suppressor genes show a gene-type specific methylation profile along the multistep carcinogenesis and that aberrant CpG island methylation tend to accumulate along the multistep carcinogenesis.</description><identifier>ISSN: 0023-6837</identifier><identifier>EISSN: 1530-0307</identifier><identifier>DOI: 10.1097/01.LAB.0000064704.53132.65</identifier><identifier>PMID: 12695555</identifier><identifier>CODEN: LAINAW</identifier><language>eng</language><publisher>New York: Elsevier Inc</publisher><subject>Adenoma - genetics ; Adenoma - pathology ; Adolescent ; Adult ; Biological and medical sciences ; Carcinoma - genetics ; Carcinoma - pathology ; Child ; Child, Preschool ; CpG Islands - genetics ; DNA Methylation ; DNA Primers - chemistry ; DNA, Neoplasm - analysis ; Gastric Mucosa - pathology ; Gastritis - genetics ; Gastritis - pathology ; Gastroenterology. Liver. Pancreas. Abdomen ; Genes, Neoplasm - genetics ; Humans ; Laboratory Medicine ; Medical sciences ; Medicine ; Medicine & Public Health ; Metaplasia - genetics ; Pathology ; Polymerase Chain Reaction ; Precancerous Conditions - genetics ; Precancerous Conditions - pathology ; Sequence Analysis, DNA ; Stomach Neoplasms - genetics ; Stomach Neoplasms - pathology ; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus ; Tumors</subject><ispartof>Laboratory investigation, 2003-04, Vol.83 (4), p.519-526</ispartof><rights>2003 United States & Canadian Academy of Pathology</rights><rights>The United States and Canadian Academy of Pathology, Inc. 2003</rights><rights>2003 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Apr 2003</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c603t-e3ae682dfc637aaf9498df1fe5fce1b5802647c9675b212f0e4be337030d6e53</citedby><cites>FETCH-LOGICAL-c603t-e3ae682dfc637aaf9498df1fe5fce1b5802647c9675b212f0e4be337030d6e53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14737269$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12695555$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kang, Gyeong Hoon</creatorcontrib><creatorcontrib>Lee, Sun</creatorcontrib><creatorcontrib>Kim, Jung-Sun</creatorcontrib><creatorcontrib>Jung, Hwoon-Yong</creatorcontrib><title>Profile of Aberrant CpG Island Methylation along Multistep Gastric Carcinogenesis</title><title>Laboratory investigation</title><addtitle>Lab Invest</addtitle><addtitle>Lab Invest</addtitle><description>The stomach is one of the organs whose epithelial cells frequently undergo aberrant methylation of CpG islands. To date, several reports on the methylation of various genes in gastric cancer (GC) have been published. However, most of these studies have 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 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: (a) genes methylated in GC only (GSTP1 and RASSF1A), (b) genes showing low methylation frequency (<12%) in CG, IM, and gastric adenoma (GA) but significantly higher methylation frequency in GC (COX-2, hMLH1, p16), (c) a gene with low and similar methylation frequency (8.8–21.3%) in four-step lesions (MGMT), (d) genes with high and similar methylation frequency (53–85%) in four-step lesions (APC and E-cadherin), and (e) genes showing an increasing tendency with or without fluctuation of the methylation frequency along the progression (DAP-kinase, p14, THBS1, and TIMP-3). 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. Aberrant methylation at multiple loci in the same lesions suggests an overall deregulation of the methylation control, which occurs early in multistep gastric carcinogenesis. Our results suggest that tumor-suppressor genes show a gene-type specific methylation profile along the multistep carcinogenesis and that aberrant CpG island methylation tend to accumulate along the multistep carcinogenesis.</description><subject>Adenoma - genetics</subject><subject>Adenoma - pathology</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Biological and medical sciences</subject><subject>Carcinoma - genetics</subject><subject>Carcinoma - pathology</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>CpG Islands - genetics</subject><subject>DNA Methylation</subject><subject>DNA Primers - chemistry</subject><subject>DNA, Neoplasm - analysis</subject><subject>Gastric Mucosa - pathology</subject><subject>Gastritis - genetics</subject><subject>Gastritis - pathology</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Genes, Neoplasm - genetics</subject><subject>Humans</subject><subject>Laboratory Medicine</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metaplasia - genetics</subject><subject>Pathology</subject><subject>Polymerase Chain Reaction</subject><subject>Precancerous Conditions - genetics</subject><subject>Precancerous Conditions - pathology</subject><subject>Sequence Analysis, DNA</subject><subject>Stomach Neoplasms - genetics</subject><subject>Stomach Neoplasms - pathology</subject><subject>Stomach. Duodenum. Small intestine. Colon. Rectum. 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Anus</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kang, Gyeong Hoon</creatorcontrib><creatorcontrib>Lee, Sun</creatorcontrib><creatorcontrib>Kim, Jung-Sun</creatorcontrib><creatorcontrib>Jung, Hwoon-Yong</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><jtitle>Laboratory investigation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kang, Gyeong Hoon</au><au>Lee, Sun</au><au>Kim, Jung-Sun</au><au>Jung, Hwoon-Yong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Profile of Aberrant CpG Island Methylation along Multistep Gastric Carcinogenesis</atitle><jtitle>Laboratory investigation</jtitle><stitle>Lab Invest</stitle><addtitle>Lab Invest</addtitle><date>2003-04-01</date><risdate>2003</risdate><volume>83</volume><issue>4</issue><spage>519</spage><epage>526</epage><pages>519-526</pages><issn>0023-6837</issn><eissn>1530-0307</eissn><coden>LAINAW</coden><abstract>The stomach is one of the organs whose epithelial cells frequently undergo aberrant methylation of CpG islands. To date, several reports on the methylation of various genes in gastric cancer (GC) have been published. However, most of these studies have 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 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: (a) genes methylated in GC only (GSTP1 and RASSF1A), (b) genes showing low methylation frequency (<12%) in CG, IM, and gastric adenoma (GA) but significantly higher methylation frequency in GC (COX-2, hMLH1, p16), (c) a gene with low and similar methylation frequency (8.8–21.3%) in four-step lesions (MGMT), (d) genes with high and similar methylation frequency (53–85%) in four-step lesions (APC and E-cadherin), and (e) genes showing an increasing tendency with or without fluctuation of the methylation frequency along the progression (DAP-kinase, p14, THBS1, and TIMP-3). 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. Aberrant methylation at multiple loci in the same lesions suggests an overall deregulation of the methylation control, which occurs early in multistep gastric carcinogenesis. Our results suggest that tumor-suppressor genes show a gene-type specific methylation profile along the multistep carcinogenesis and that aberrant CpG island methylation tend to accumulate along the multistep carcinogenesis.</abstract><cop>New York</cop><pub>Elsevier Inc</pub><pmid>12695555</pmid><doi>10.1097/01.LAB.0000064704.53132.65</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adenoma - genetics Adenoma - pathology Adolescent Adult Biological and medical sciences Carcinoma - genetics Carcinoma - pathology Child Child, Preschool CpG Islands - genetics DNA Methylation DNA Primers - chemistry DNA, Neoplasm - analysis Gastric Mucosa - pathology Gastritis - genetics Gastritis - pathology Gastroenterology. Liver. Pancreas. Abdomen Genes, Neoplasm - genetics Humans Laboratory Medicine Medical sciences Medicine Medicine & Public Health Metaplasia - genetics Pathology Polymerase Chain Reaction Precancerous Conditions - genetics Precancerous Conditions - pathology Sequence Analysis, DNA Stomach Neoplasms - genetics Stomach Neoplasms - pathology Stomach. Duodenum. Small intestine. Colon. Rectum. Anus Tumors |
| title | Profile of Aberrant CpG Island Methylation along Multistep Gastric Carcinogenesis |
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