Extensive somatic microsatellite mutations in normal human tissue
Microsatellite (MS) instability occurs in tumors with DNA mismatch repair (MMR) deficiencies but is typically absent in adjacent normal tissue. However, MS mutations have been observed in normal tissues from rare individuals with congenital MMR deficiencies. Autopsy tissues from a 4-year-old with co...
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| Veröffentlicht in: | Cancer research (Chicago, Ill.) Ill.), 2001-06, Vol.61 (11), p.4541-4544 |
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| container_title | Cancer research (Chicago, Ill.) |
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| creator | VILKKI, Susa TSAO, Jen-Lan LOUKOLA, Anu PÖYHÖNEN, Minna VIERIMAA, Outi HERVA, Riitta AALTONEN, Lauri A SHIBATA, Darryl |
| description | Microsatellite (MS) instability occurs in tumors with DNA mismatch repair (MMR) deficiencies but is typically absent in adjacent normal tissue. However, MS mutations have been observed in normal tissues from rare individuals with congenital MMR deficiencies. Autopsy tissues from a 4-year-old with congenital MMR deficiency (MLH1-/-) were examined for MS mutations. Insertions and deletions were observed in CA-repeat MS loci. Approximately 0.26 to 1.4 mutations per MS locus per cell were estimated to be present in normal heart, lymph node, kidney, and bladder epithelium. These findings illustrate that phenotypically normal MMR-deficient cells commonly accumulate MS mutations. Loss of MMR and the accumulation of some MS mutations may occur early in MMR-deficient tumor progression, even before a gatekeeper mutation. |
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However, MS mutations have been observed in normal tissues from rare individuals with congenital MMR deficiencies. Autopsy tissues from a 4-year-old with congenital MMR deficiency (MLH1-/-) were examined for MS mutations. Insertions and deletions were observed in CA-repeat MS loci. Approximately 0.26 to 1.4 mutations per MS locus per cell were estimated to be present in normal heart, lymph node, kidney, and bladder epithelium. These findings illustrate that phenotypically normal MMR-deficient cells commonly accumulate MS mutations. Loss of MMR and the accumulation of some MS mutations may occur early in MMR-deficient tumor progression, even before a gatekeeper mutation.</description><identifier>ISSN: 0008-5472</identifier><identifier>EISSN: 1538-7445</identifier><identifier>PMID: 11389087</identifier><identifier>CODEN: CNREA8</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Adaptor Proteins, Signal Transducing ; Base Pair Mismatch ; Biological and medical sciences ; Brain Neoplasms - genetics ; Carrier Proteins ; Child, Preschool ; DNA - genetics ; DNA - isolation & purification ; DNA Repair - genetics ; Female ; Fundamental and applied biological sciences. Psychology ; General aspects ; Glioma - genetics ; Humans ; Microsatellite Repeats - genetics ; Molecular and cellular biology ; Mutation ; MutL Protein Homolog 1 ; Neoplasm Proteins - genetics ; Nuclear Proteins</subject><ispartof>Cancer research (Chicago, Ill.), 2001-06, Vol.61 (11), p.4541-4544</ispartof><rights>2001 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1067509$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11389087$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>VILKKI, Susa</creatorcontrib><creatorcontrib>TSAO, Jen-Lan</creatorcontrib><creatorcontrib>LOUKOLA, Anu</creatorcontrib><creatorcontrib>PÖYHÖNEN, Minna</creatorcontrib><creatorcontrib>VIERIMAA, Outi</creatorcontrib><creatorcontrib>HERVA, Riitta</creatorcontrib><creatorcontrib>AALTONEN, Lauri A</creatorcontrib><creatorcontrib>SHIBATA, Darryl</creatorcontrib><title>Extensive somatic microsatellite mutations in normal human tissue</title><title>Cancer research (Chicago, Ill.)</title><addtitle>Cancer Res</addtitle><description>Microsatellite (MS) instability occurs in tumors with DNA mismatch repair (MMR) deficiencies but is typically absent in adjacent normal tissue. However, MS mutations have been observed in normal tissues from rare individuals with congenital MMR deficiencies. Autopsy tissues from a 4-year-old with congenital MMR deficiency (MLH1-/-) were examined for MS mutations. Insertions and deletions were observed in CA-repeat MS loci. Approximately 0.26 to 1.4 mutations per MS locus per cell were estimated to be present in normal heart, lymph node, kidney, and bladder epithelium. These findings illustrate that phenotypically normal MMR-deficient cells commonly accumulate MS mutations. Loss of MMR and the accumulation of some MS mutations may occur early in MMR-deficient tumor progression, even before a gatekeeper mutation.</description><subject>Adaptor Proteins, Signal Transducing</subject><subject>Base Pair Mismatch</subject><subject>Biological and medical sciences</subject><subject>Brain Neoplasms - genetics</subject><subject>Carrier Proteins</subject><subject>Child, Preschool</subject><subject>DNA - genetics</subject><subject>DNA - isolation & purification</subject><subject>DNA Repair - genetics</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>General aspects</subject><subject>Glioma - genetics</subject><subject>Humans</subject><subject>Microsatellite Repeats - genetics</subject><subject>Molecular and cellular biology</subject><subject>Mutation</subject><subject>MutL Protein Homolog 1</subject><subject>Neoplasm Proteins - genetics</subject><subject>Nuclear Proteins</subject><issn>0008-5472</issn><issn>1538-7445</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0E1LxDAQBuAgiruu_gXJQbwVkqbZJMdlWT9gwYueyyRN2UiTrp1U9N9bseLR0zDDw8vLnJAll0IXqqrkKVkyxnQhK1UuyAXi67RKzuQ5WXAutGFaLclm95F9wvDuKfYRcnA0Bjf0CNl3XciexjFP5z4hDYmmfojQ0cMYIdEcEEd_Sc5a6NBfzXNFXu52z9uHYv90_7jd7IuDYDwXhglwnLWmrNZagPaitWVpW8d91RijDFjrRcWFFA03ohGOWSanxsCsM64VK3L7k3sc-rfRY65jQDeVhOT7EWvFtBGK638hV_q7hJrg9QxHG31TH4cQYfisf78zgZsZADro2gGSC_jn2FpJZsQXiqxupQ</recordid><startdate>20010601</startdate><enddate>20010601</enddate><creator>VILKKI, Susa</creator><creator>TSAO, Jen-Lan</creator><creator>LOUKOLA, Anu</creator><creator>PÖYHÖNEN, Minna</creator><creator>VIERIMAA, Outi</creator><creator>HERVA, Riitta</creator><creator>AALTONEN, Lauri A</creator><creator>SHIBATA, Darryl</creator><general>American Association for Cancer Research</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20010601</creationdate><title>Extensive somatic microsatellite mutations in normal human tissue</title><author>VILKKI, Susa ; TSAO, Jen-Lan ; LOUKOLA, Anu ; PÖYHÖNEN, Minna ; VIERIMAA, Outi ; HERVA, Riitta ; AALTONEN, Lauri A ; SHIBATA, Darryl</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h301t-903ac10f924683a8e3fb22bfc1e4d9979abbe341353d193d3c0b05005a0bc9cf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Adaptor Proteins, Signal Transducing</topic><topic>Base Pair Mismatch</topic><topic>Biological and medical sciences</topic><topic>Brain Neoplasms - genetics</topic><topic>Carrier Proteins</topic><topic>Child, Preschool</topic><topic>DNA - genetics</topic><topic>DNA - isolation & purification</topic><topic>DNA Repair - genetics</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>General aspects</topic><topic>Glioma - genetics</topic><topic>Humans</topic><topic>Microsatellite Repeats - genetics</topic><topic>Molecular and cellular biology</topic><topic>Mutation</topic><topic>MutL Protein Homolog 1</topic><topic>Neoplasm Proteins - genetics</topic><topic>Nuclear Proteins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>VILKKI, Susa</creatorcontrib><creatorcontrib>TSAO, Jen-Lan</creatorcontrib><creatorcontrib>LOUKOLA, Anu</creatorcontrib><creatorcontrib>PÖYHÖNEN, Minna</creatorcontrib><creatorcontrib>VIERIMAA, Outi</creatorcontrib><creatorcontrib>HERVA, Riitta</creatorcontrib><creatorcontrib>AALTONEN, Lauri A</creatorcontrib><creatorcontrib>SHIBATA, Darryl</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</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>Cancer research (Chicago, Ill.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>VILKKI, Susa</au><au>TSAO, Jen-Lan</au><au>LOUKOLA, Anu</au><au>PÖYHÖNEN, Minna</au><au>VIERIMAA, Outi</au><au>HERVA, Riitta</au><au>AALTONEN, Lauri A</au><au>SHIBATA, Darryl</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Extensive somatic microsatellite mutations in normal human tissue</atitle><jtitle>Cancer research (Chicago, Ill.)</jtitle><addtitle>Cancer Res</addtitle><date>2001-06-01</date><risdate>2001</risdate><volume>61</volume><issue>11</issue><spage>4541</spage><epage>4544</epage><pages>4541-4544</pages><issn>0008-5472</issn><eissn>1538-7445</eissn><coden>CNREA8</coden><abstract>Microsatellite (MS) instability occurs in tumors with DNA mismatch repair (MMR) deficiencies but is typically absent in adjacent normal tissue. However, MS mutations have been observed in normal tissues from rare individuals with congenital MMR deficiencies. Autopsy tissues from a 4-year-old with congenital MMR deficiency (MLH1-/-) were examined for MS mutations. Insertions and deletions were observed in CA-repeat MS loci. Approximately 0.26 to 1.4 mutations per MS locus per cell were estimated to be present in normal heart, lymph node, kidney, and bladder epithelium. These findings illustrate that phenotypically normal MMR-deficient cells commonly accumulate MS mutations. Loss of MMR and the accumulation of some MS mutations may occur early in MMR-deficient tumor progression, even before a gatekeeper mutation.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>11389087</pmid><tpages>4</tpages></addata></record> |
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| subjects | Adaptor Proteins, Signal Transducing Base Pair Mismatch Biological and medical sciences Brain Neoplasms - genetics Carrier Proteins Child, Preschool DNA - genetics DNA - isolation & purification DNA Repair - genetics Female Fundamental and applied biological sciences. Psychology General aspects Glioma - genetics Humans Microsatellite Repeats - genetics Molecular and cellular biology Mutation MutL Protein Homolog 1 Neoplasm Proteins - genetics Nuclear Proteins |
| title | Extensive somatic microsatellite mutations in normal human tissue |
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