Genetic and epigenetic modification of mismatch repair genes hMSH2 and hMLH1 in sporadic breast cancer with microsatellite instability
Breast cancer is the most common cancer in women, but its pathogenesis is still unclear. Microsatellite instability (MSI) has been identified in breast cancer cells, suggesting an association with mismatch repair defects. To test this hypothesis, we investigated MSI, protein expression of hMSH2 and...
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| Veröffentlicht in: | Oncogene 2002-08, Vol.21 (37), p.5696-5703 |
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| creator | Murata, Hiroaki Khattar, Nada H Kang, Yuna Gu, Liya Li, Guo-Min |
| description | Breast cancer is the most common cancer in women, but its pathogenesis is still unclear. Microsatellite instability (MSI) has been identified in breast cancer cells, suggesting an association with mismatch repair defects. To test this hypothesis, we investigated MSI, protein expression of hMSH2 and hMLH1, as well as genetic and epigenetic modifications of these two genes in 32 sporadic breast tumors. MSI was identified in 15 cases. Immunohistochemistry analysis revealed that all MSI cases but one had lower than normal expression of hMSH2 (nine cases), hMLH1 (12 cases), or both (seven cases). In tumors with MSI, both genetic and epigenetic modifications of these mismatch repair genes were also identified. Eight cases harbored mutations or polymorphisms in hMSH2 and hMLH1, and 10 exhibited hypermethylation in the promoter region of hMLH1. These results suggest that both genetic and epigenetic alterations of hMSH2 and especially of hMLH1 contribute to genomic instability and tumorigenesis in sporadic breast cancer. |
| doi_str_mv | 10.1038/sj.onc.1205683 |
| format | Article |
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Microsatellite instability (MSI) has been identified in breast cancer cells, suggesting an association with mismatch repair defects. To test this hypothesis, we investigated MSI, protein expression of hMSH2 and hMLH1, as well as genetic and epigenetic modifications of these two genes in 32 sporadic breast tumors. MSI was identified in 15 cases. Immunohistochemistry analysis revealed that all MSI cases but one had lower than normal expression of hMSH2 (nine cases), hMLH1 (12 cases), or both (seven cases). In tumors with MSI, both genetic and epigenetic modifications of these mismatch repair genes were also identified. Eight cases harbored mutations or polymorphisms in hMSH2 and hMLH1, and 10 exhibited hypermethylation in the promoter region of hMLH1. These results suggest that both genetic and epigenetic alterations of hMSH2 and especially of hMLH1 contribute to genomic instability and tumorigenesis in sporadic breast cancer.</description><identifier>ISSN: 0950-9232</identifier><identifier>EISSN: 1476-5594</identifier><identifier>DOI: 10.1038/sj.onc.1205683</identifier><identifier>PMID: 12173039</identifier><identifier>CODEN: ONCNES</identifier><language>eng</language><publisher>England: Nature Publishing Group</publisher><subject>Adaptor Proteins, Signal Transducing ; Base Pair Mismatch ; Breast cancer ; Breast Neoplasms - genetics ; Carrier Proteins ; DNA Methylation ; DNA Repair - genetics ; DNA-Binding Proteins ; Endometrial cancer ; Epigenetics ; Female ; Genes ; Genomic instability ; Humans ; Immunohistochemistry ; Medicine ; Microsatellite instability ; Microsatellite Repeats ; Mismatch repair ; Mutation ; MutL Protein Homolog 1 ; MutS Homolog 2 Protein ; Neoplasm Proteins - genetics ; Nuclear Proteins ; Promoter Regions, Genetic ; Protein expression ; Proto-Oncogene Proteins - genetics ; Tumorigenesis ; Tumors ; Yeast</subject><ispartof>Oncogene, 2002-08, Vol.21 (37), p.5696-5703</ispartof><rights>Copyright Nature Publishing Group Aug 22, 2002</rights><rights>Macmillan Publishers Limited 2002.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c377t-313570d1c3a2c2eef0a856f040c775234f695e7ef6de84ef4ab71a9886ba08f13</citedby><cites>FETCH-LOGICAL-c377t-313570d1c3a2c2eef0a856f040c775234f695e7ef6de84ef4ab71a9886ba08f13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12173039$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Murata, Hiroaki</creatorcontrib><creatorcontrib>Khattar, Nada H</creatorcontrib><creatorcontrib>Kang, Yuna</creatorcontrib><creatorcontrib>Gu, Liya</creatorcontrib><creatorcontrib>Li, Guo-Min</creatorcontrib><title>Genetic and epigenetic modification of mismatch repair genes hMSH2 and hMLH1 in sporadic breast cancer with microsatellite instability</title><title>Oncogene</title><addtitle>Oncogene</addtitle><description>Breast cancer is the most common cancer in women, but its pathogenesis is still unclear. Microsatellite instability (MSI) has been identified in breast cancer cells, suggesting an association with mismatch repair defects. To test this hypothesis, we investigated MSI, protein expression of hMSH2 and hMLH1, as well as genetic and epigenetic modifications of these two genes in 32 sporadic breast tumors. MSI was identified in 15 cases. Immunohistochemistry analysis revealed that all MSI cases but one had lower than normal expression of hMSH2 (nine cases), hMLH1 (12 cases), or both (seven cases). In tumors with MSI, both genetic and epigenetic modifications of these mismatch repair genes were also identified. Eight cases harbored mutations or polymorphisms in hMSH2 and hMLH1, and 10 exhibited hypermethylation in the promoter region of hMLH1. These results suggest that both genetic and epigenetic alterations of hMSH2 and especially of hMLH1 contribute to genomic instability and tumorigenesis in sporadic breast cancer.</description><subject>Adaptor Proteins, Signal Transducing</subject><subject>Base Pair Mismatch</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - genetics</subject><subject>Carrier Proteins</subject><subject>DNA Methylation</subject><subject>DNA Repair - genetics</subject><subject>DNA-Binding Proteins</subject><subject>Endometrial cancer</subject><subject>Epigenetics</subject><subject>Female</subject><subject>Genes</subject><subject>Genomic instability</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Medicine</subject><subject>Microsatellite instability</subject><subject>Microsatellite Repeats</subject><subject>Mismatch repair</subject><subject>Mutation</subject><subject>MutL Protein Homolog 1</subject><subject>MutS Homolog 2 Protein</subject><subject>Neoplasm Proteins - genetics</subject><subject>Nuclear Proteins</subject><subject>Promoter Regions, Genetic</subject><subject>Protein expression</subject><subject>Proto-Oncogene Proteins - genetics</subject><subject>Tumorigenesis</subject><subject>Tumors</subject><subject>Yeast</subject><issn>0950-9232</issn><issn>1476-5594</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFkV1rFDEUhoNY7LZ666UEhd7Nmo_Jx1xKsV1hSy_U65DJnLhZdiZjkqX0D_i7zbYDgiBe5QSe83DOeRF6S8maEq4_5v06Tm5NGRFS8xdoRVslGyG69iVakU6QpmOcnaOLnPeEENUR9gqdU0YVJ7xboV-3MEEJDttpwDCHH8t3jEPwwdkS4oSjx2PIoy1uhxPMNiR84jLe3X3dsKfW3d12Q3GYcJ5jskM19AlsLtjZyUHCD6HsqsSlmG2BwyEUqHQutg-1fnyNzrw9ZHizvJfo-83nb9ebZnt_--X607ZxXKnScMqFIgN13DLHADyxWkhPWuKUEoy3XnYCFHg5gG7Bt7ZX1HZay94S7Sm_RFfP3jnFn0fIxdTFXJ3HThCP2SjaadUx8V-QaklYS07GD3-B-3hMU13CMNlSzpWUvFLv_0kxxamgQlZo_QydrpQTeDOnMNr0aCgxp7RN3puatlnSrg3vFuuxH2H4gy_x8t_zmaZc</recordid><startdate>20020822</startdate><enddate>20020822</enddate><creator>Murata, Hiroaki</creator><creator>Khattar, Nada H</creator><creator>Kang, Yuna</creator><creator>Gu, Liya</creator><creator>Li, Guo-Min</creator><general>Nature Publishing Group</general><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>3V.</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20020822</creationdate><title>Genetic and epigenetic modification of mismatch repair genes hMSH2 and hMLH1 in sporadic breast cancer with microsatellite instability</title><author>Murata, Hiroaki ; Khattar, Nada H ; Kang, Yuna ; Gu, Liya ; Li, Guo-Min</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c377t-313570d1c3a2c2eef0a856f040c775234f695e7ef6de84ef4ab71a9886ba08f13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Adaptor Proteins, Signal Transducing</topic><topic>Base Pair Mismatch</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - genetics</topic><topic>Carrier Proteins</topic><topic>DNA Methylation</topic><topic>DNA Repair - genetics</topic><topic>DNA-Binding Proteins</topic><topic>Endometrial cancer</topic><topic>Epigenetics</topic><topic>Female</topic><topic>Genes</topic><topic>Genomic instability</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Medicine</topic><topic>Microsatellite instability</topic><topic>Microsatellite Repeats</topic><topic>Mismatch repair</topic><topic>Mutation</topic><topic>MutL Protein Homolog 1</topic><topic>MutS Homolog 2 Protein</topic><topic>Neoplasm Proteins - genetics</topic><topic>Nuclear Proteins</topic><topic>Promoter Regions, Genetic</topic><topic>Protein expression</topic><topic>Proto-Oncogene Proteins - genetics</topic><topic>Tumorigenesis</topic><topic>Tumors</topic><topic>Yeast</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Murata, Hiroaki</creatorcontrib><creatorcontrib>Khattar, Nada H</creatorcontrib><creatorcontrib>Kang, Yuna</creatorcontrib><creatorcontrib>Gu, Liya</creatorcontrib><creatorcontrib>Li, Guo-Min</creatorcontrib><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>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</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>Research Library (Alumni Edition)</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>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>Research Library Prep</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>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</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><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Oncogene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Murata, Hiroaki</au><au>Khattar, Nada H</au><au>Kang, Yuna</au><au>Gu, Liya</au><au>Li, Guo-Min</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic and epigenetic modification of mismatch repair genes hMSH2 and hMLH1 in sporadic breast cancer with microsatellite instability</atitle><jtitle>Oncogene</jtitle><addtitle>Oncogene</addtitle><date>2002-08-22</date><risdate>2002</risdate><volume>21</volume><issue>37</issue><spage>5696</spage><epage>5703</epage><pages>5696-5703</pages><issn>0950-9232</issn><eissn>1476-5594</eissn><coden>ONCNES</coden><abstract>Breast cancer is the most common cancer in women, but its pathogenesis is still unclear. Microsatellite instability (MSI) has been identified in breast cancer cells, suggesting an association with mismatch repair defects. To test this hypothesis, we investigated MSI, protein expression of hMSH2 and hMLH1, as well as genetic and epigenetic modifications of these two genes in 32 sporadic breast tumors. MSI was identified in 15 cases. Immunohistochemistry analysis revealed that all MSI cases but one had lower than normal expression of hMSH2 (nine cases), hMLH1 (12 cases), or both (seven cases). In tumors with MSI, both genetic and epigenetic modifications of these mismatch repair genes were also identified. Eight cases harbored mutations or polymorphisms in hMSH2 and hMLH1, and 10 exhibited hypermethylation in the promoter region of hMLH1. These results suggest that both genetic and epigenetic alterations of hMSH2 and especially of hMLH1 contribute to genomic instability and tumorigenesis in sporadic breast cancer.</abstract><cop>England</cop><pub>Nature Publishing Group</pub><pmid>12173039</pmid><doi>10.1038/sj.onc.1205683</doi><tpages>8</tpages></addata></record> |
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| subjects | Adaptor Proteins, Signal Transducing Base Pair Mismatch Breast cancer Breast Neoplasms - genetics Carrier Proteins DNA Methylation DNA Repair - genetics DNA-Binding Proteins Endometrial cancer Epigenetics Female Genes Genomic instability Humans Immunohistochemistry Medicine Microsatellite instability Microsatellite Repeats Mismatch repair Mutation MutL Protein Homolog 1 MutS Homolog 2 Protein Neoplasm Proteins - genetics Nuclear Proteins Promoter Regions, Genetic Protein expression Proto-Oncogene Proteins - genetics Tumorigenesis Tumors Yeast |
| title | Genetic and epigenetic modification of mismatch repair genes hMSH2 and hMLH1 in sporadic breast cancer with microsatellite instability |
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