Differential involvement of the hypermethylator phenotype in hereditary and sporadic colorectal cancers with high-frequency microsatellite instability
High‐frequency microsatellite instability (MSI‐H) due to defective DNA mismatch repair occurs in the majority of hereditary nonpolyposis colorectal cancers (HNPCCs) and in a subset of sporadic malignant tumors. Clinicopathologic and genotypic features of MSI‐H colorectal tumors in HNPCC patients and...
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Veröffentlicht in: | Genes chromosomes & cancer 2002-03, Vol.33 (3), p.322-325 |
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description | High‐frequency microsatellite instability (MSI‐H) due to defective DNA mismatch repair occurs in the majority of hereditary nonpolyposis colorectal cancers (HNPCCs) and in a subset of sporadic malignant tumors. Clinicopathologic and genotypic features of MSI‐H colorectal tumors in HNPCC patients and those in sporadic cases are very similar but not identical. Correlation between the MSI phenotype and aberrant DNA methylation has been highlighted recently. A strong association between MSI and CpG island methylation has been well characterized in sporadic colorectal cancers with MSI‐H but not in those of hereditary origin. To address the issue, we analyzed hereditary and sporadic colorectal cancers for aberrant DNA methylation of target genes using methylation‐specific polymerase chain reaction. DNA methylation of the MLH1, CDKN2A, MGMT, THBS1, RARB, APC, and p14ARF genes was found in 0%, 23%, 10%, 3%, 73%, 53%, and 33% of 30 MSI‐H cancers in HNPCC patients and in 80%, 55%, 23%, 23%, 58%, 35%, and 50% of 40 sporadic colorectal cancers with MSI‐H, respectively. Cases showing methylation at three or more loci of six genes other than MLH1 were defined as CpG island methylator phenotype–positive (CIMP+), and 23% of HNPCC tumors and 53% of sporadic cancers with MSI‐H were CIMP+ (P = 0.018). Differences in the extent of CpG island methylation, coupled with the differential involvement of several genes by methylation, in HNPCC tumors and sporadic MSI‐H colorectal cancers may be associated with diverging developmental pathways in hereditary and sporadic cancers despite similar MSI‐H phenotypes. © 2002 Wiley‐Liss, Inc. |
doi_str_mv | 10.1002/gcc.10010 |
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Clinicopathologic and genotypic features of MSI‐H colorectal tumors in HNPCC patients and those in sporadic cases are very similar but not identical. Correlation between the MSI phenotype and aberrant DNA methylation has been highlighted recently. A strong association between MSI and CpG island methylation has been well characterized in sporadic colorectal cancers with MSI‐H but not in those of hereditary origin. To address the issue, we analyzed hereditary and sporadic colorectal cancers for aberrant DNA methylation of target genes using methylation‐specific polymerase chain reaction. DNA methylation of the MLH1, CDKN2A, MGMT, THBS1, RARB, APC, and p14ARF genes was found in 0%, 23%, 10%, 3%, 73%, 53%, and 33% of 30 MSI‐H cancers in HNPCC patients and in 80%, 55%, 23%, 23%, 58%, 35%, and 50% of 40 sporadic colorectal cancers with MSI‐H, respectively. Cases showing methylation at three or more loci of six genes other than MLH1 were defined as CpG island methylator phenotype–positive (CIMP+), and 23% of HNPCC tumors and 53% of sporadic cancers with MSI‐H were CIMP+ (P = 0.018). Differences in the extent of CpG island methylation, coupled with the differential involvement of several genes by methylation, in HNPCC tumors and sporadic MSI‐H colorectal cancers may be associated with diverging developmental pathways in hereditary and sporadic cancers despite similar MSI‐H phenotypes. © 2002 Wiley‐Liss, Inc.</description><identifier>ISSN: 1045-2257</identifier><identifier>EISSN: 1098-2264</identifier><identifier>DOI: 10.1002/gcc.10010</identifier><identifier>PMID: 11807990</identifier><language>eng</language><publisher>New York: John Wiley & Sons, Inc</publisher><subject>Adenocarcinoma - genetics ; APC gene ; CDKN2A gene ; Colorectal Neoplasms - genetics ; Colorectal Neoplasms, Hereditary Nonpolyposis - genetics ; CpG Islands - genetics ; DNA Methylation ; Female ; Humans ; MGMT gene ; Microsatellite Repeats - genetics ; MLH1 gene ; p14ARF gene ; Phenotype ; RARB gene ; THBS1 gene</subject><ispartof>Genes chromosomes & cancer, 2002-03, Vol.33 (3), p.322-325</ispartof><rights>Copyright © 2002 Wiley‐Liss, Inc.</rights><rights>Copyright 2002 Wiley-Liss, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4190-96d68d1c7cadf74aa911257dd2f30de7bfba9d17c1d44c1d183677ca5cc90d5f3</citedby><cites>FETCH-LOGICAL-c4190-96d68d1c7cadf74aa911257dd2f30de7bfba9d17c1d44c1d183677ca5cc90d5f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fgcc.10010$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fgcc.10010$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1416,27923,27924,45573,45574</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11807990$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yamamoto, Hiroyuki</creatorcontrib><creatorcontrib>Min, Yongfen</creatorcontrib><creatorcontrib>Itoh, Fumio</creatorcontrib><creatorcontrib>Imsumran, Arisa</creatorcontrib><creatorcontrib>Horiuchi, Shina</creatorcontrib><creatorcontrib>Yoshida, Mio</creatorcontrib><creatorcontrib>Iku, Shouhei</creatorcontrib><creatorcontrib>Fukushima, Hiroshi</creatorcontrib><creatorcontrib>Imai, Kohzoh</creatorcontrib><title>Differential involvement of the hypermethylator phenotype in hereditary and sporadic colorectal cancers with high-frequency microsatellite instability</title><title>Genes chromosomes & cancer</title><addtitle>Genes Chromosom. Cancer</addtitle><description>High‐frequency microsatellite instability (MSI‐H) due to defective DNA mismatch repair occurs in the majority of hereditary nonpolyposis colorectal cancers (HNPCCs) and in a subset of sporadic malignant tumors. Clinicopathologic and genotypic features of MSI‐H colorectal tumors in HNPCC patients and those in sporadic cases are very similar but not identical. Correlation between the MSI phenotype and aberrant DNA methylation has been highlighted recently. A strong association between MSI and CpG island methylation has been well characterized in sporadic colorectal cancers with MSI‐H but not in those of hereditary origin. To address the issue, we analyzed hereditary and sporadic colorectal cancers for aberrant DNA methylation of target genes using methylation‐specific polymerase chain reaction. DNA methylation of the MLH1, CDKN2A, MGMT, THBS1, RARB, APC, and p14ARF genes was found in 0%, 23%, 10%, 3%, 73%, 53%, and 33% of 30 MSI‐H cancers in HNPCC patients and in 80%, 55%, 23%, 23%, 58%, 35%, and 50% of 40 sporadic colorectal cancers with MSI‐H, respectively. Cases showing methylation at three or more loci of six genes other than MLH1 were defined as CpG island methylator phenotype–positive (CIMP+), and 23% of HNPCC tumors and 53% of sporadic cancers with MSI‐H were CIMP+ (P = 0.018). Differences in the extent of CpG island methylation, coupled with the differential involvement of several genes by methylation, in HNPCC tumors and sporadic MSI‐H colorectal cancers may be associated with diverging developmental pathways in hereditary and sporadic cancers despite similar MSI‐H phenotypes. © 2002 Wiley‐Liss, Inc.</description><subject>Adenocarcinoma - genetics</subject><subject>APC gene</subject><subject>CDKN2A gene</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Colorectal Neoplasms, Hereditary Nonpolyposis - genetics</subject><subject>CpG Islands - genetics</subject><subject>DNA Methylation</subject><subject>Female</subject><subject>Humans</subject><subject>MGMT gene</subject><subject>Microsatellite Repeats - genetics</subject><subject>MLH1 gene</subject><subject>p14ARF gene</subject><subject>Phenotype</subject><subject>RARB gene</subject><subject>THBS1 gene</subject><issn>1045-2257</issn><issn>1098-2264</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcFu1DAQhi0EoqVw4AWQT0gcQu3EieMjBFgqlcIBBDfLa48bQxKntrclL8Lz4nQXekJc7H-sb37N-EfoKSUvKSHl6aXWq6DkHjqmRLRFWTbs_qpZnXXNj9CjGL8TQppK1A_REaUt4UKQY_TrjbMWAkzJqQG76doP1zDmEnuLUw-4X2YII6R-GVTyAc89TD7lxwzjPncal1RYsJoMjrMPyjiNtR98AJ2ypVaThhDxjUs97t1lX9gAVzuY9IJHp4OPKsEwuLQaxqS2LuvlMXpg1RDhyeE-QV_evf3cvS_OP27OulfnhWZUkEI0pmkN1VwrYzlTSlCa1zWmtBUxwLd2q4ShXFPDWD5oWzU8w7XWgpjaVifo-d53Dj4PFZMcXdR5HjWB30XJKaNl05D_grQtBWdlncEXe3BdLQawcg5uzD8kKZFrWjKnJW_Tyuyzg-luO4K5Iw_xZOB0D9y4AZZ_O8lN1_2xLPYdLib4-bdDhR-y4RWv5deLjew-kE81K1_Lb9VvHZ-yng</recordid><startdate>200203</startdate><enddate>200203</enddate><creator>Yamamoto, Hiroyuki</creator><creator>Min, Yongfen</creator><creator>Itoh, Fumio</creator><creator>Imsumran, Arisa</creator><creator>Horiuchi, Shina</creator><creator>Yoshida, Mio</creator><creator>Iku, Shouhei</creator><creator>Fukushima, Hiroshi</creator><creator>Imai, Kohzoh</creator><general>John Wiley & Sons, Inc</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>200203</creationdate><title>Differential involvement of the hypermethylator phenotype in hereditary and sporadic colorectal cancers with high-frequency microsatellite instability</title><author>Yamamoto, Hiroyuki ; Min, Yongfen ; Itoh, Fumio ; Imsumran, Arisa ; Horiuchi, Shina ; Yoshida, Mio ; Iku, Shouhei ; Fukushima, Hiroshi ; Imai, Kohzoh</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4190-96d68d1c7cadf74aa911257dd2f30de7bfba9d17c1d44c1d183677ca5cc90d5f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Adenocarcinoma - genetics</topic><topic>APC gene</topic><topic>CDKN2A gene</topic><topic>Colorectal Neoplasms - genetics</topic><topic>Colorectal Neoplasms, Hereditary Nonpolyposis - genetics</topic><topic>CpG Islands - genetics</topic><topic>DNA Methylation</topic><topic>Female</topic><topic>Humans</topic><topic>MGMT gene</topic><topic>Microsatellite Repeats - genetics</topic><topic>MLH1 gene</topic><topic>p14ARF gene</topic><topic>Phenotype</topic><topic>RARB gene</topic><topic>THBS1 gene</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yamamoto, Hiroyuki</creatorcontrib><creatorcontrib>Min, Yongfen</creatorcontrib><creatorcontrib>Itoh, Fumio</creatorcontrib><creatorcontrib>Imsumran, Arisa</creatorcontrib><creatorcontrib>Horiuchi, Shina</creatorcontrib><creatorcontrib>Yoshida, Mio</creatorcontrib><creatorcontrib>Iku, Shouhei</creatorcontrib><creatorcontrib>Fukushima, Hiroshi</creatorcontrib><creatorcontrib>Imai, Kohzoh</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Genes chromosomes & cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yamamoto, Hiroyuki</au><au>Min, Yongfen</au><au>Itoh, Fumio</au><au>Imsumran, Arisa</au><au>Horiuchi, Shina</au><au>Yoshida, Mio</au><au>Iku, Shouhei</au><au>Fukushima, Hiroshi</au><au>Imai, Kohzoh</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Differential involvement of the hypermethylator phenotype in hereditary and sporadic colorectal cancers with high-frequency microsatellite instability</atitle><jtitle>Genes chromosomes & cancer</jtitle><addtitle>Genes Chromosom. Cancer</addtitle><date>2002-03</date><risdate>2002</risdate><volume>33</volume><issue>3</issue><spage>322</spage><epage>325</epage><pages>322-325</pages><issn>1045-2257</issn><eissn>1098-2264</eissn><abstract>High‐frequency microsatellite instability (MSI‐H) due to defective DNA mismatch repair occurs in the majority of hereditary nonpolyposis colorectal cancers (HNPCCs) and in a subset of sporadic malignant tumors. Clinicopathologic and genotypic features of MSI‐H colorectal tumors in HNPCC patients and those in sporadic cases are very similar but not identical. Correlation between the MSI phenotype and aberrant DNA methylation has been highlighted recently. A strong association between MSI and CpG island methylation has been well characterized in sporadic colorectal cancers with MSI‐H but not in those of hereditary origin. To address the issue, we analyzed hereditary and sporadic colorectal cancers for aberrant DNA methylation of target genes using methylation‐specific polymerase chain reaction. DNA methylation of the MLH1, CDKN2A, MGMT, THBS1, RARB, APC, and p14ARF genes was found in 0%, 23%, 10%, 3%, 73%, 53%, and 33% of 30 MSI‐H cancers in HNPCC patients and in 80%, 55%, 23%, 23%, 58%, 35%, and 50% of 40 sporadic colorectal cancers with MSI‐H, respectively. Cases showing methylation at three or more loci of six genes other than MLH1 were defined as CpG island methylator phenotype–positive (CIMP+), and 23% of HNPCC tumors and 53% of sporadic cancers with MSI‐H were CIMP+ (P = 0.018). Differences in the extent of CpG island methylation, coupled with the differential involvement of several genes by methylation, in HNPCC tumors and sporadic MSI‐H colorectal cancers may be associated with diverging developmental pathways in hereditary and sporadic cancers despite similar MSI‐H phenotypes. © 2002 Wiley‐Liss, Inc.</abstract><cop>New York</cop><pub>John Wiley & Sons, Inc</pub><pmid>11807990</pmid><doi>10.1002/gcc.10010</doi><tpages>4</tpages></addata></record> |
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subjects | Adenocarcinoma - genetics APC gene CDKN2A gene Colorectal Neoplasms - genetics Colorectal Neoplasms, Hereditary Nonpolyposis - genetics CpG Islands - genetics DNA Methylation Female Humans MGMT gene Microsatellite Repeats - genetics MLH1 gene p14ARF gene Phenotype RARB gene THBS1 gene |
title | Differential involvement of the hypermethylator phenotype in hereditary and sporadic colorectal cancers with high-frequency microsatellite instability |
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