Mutations at coding mononucleotide repeats in gastric cancer with the microsatellite mutator phenotype
We analysed 50 gastric carcinomas (GCs) to verify whether mutations at coding repeats were associated with microsatellite instability (MSI). The tumors included: ten cases with no MSI, 14 cases with MSI = 1 locus, 13 cases with MSI = two loci and 13 cases with MSI > or = 3 loci. We investigated c...
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| Veröffentlicht in: | Oncogene 1998-05, Vol.16 (21), p.2767-2772 |
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| creator | OTTINI, L FALCHETTI, M D'AMICO, C AMOROSI, A SAIEVA, C MASALA, G FRATI, L CAMA, A PALLI, D MARIANI-COSTANTINI, R |
| description | We analysed 50 gastric carcinomas (GCs) to verify whether mutations at coding repeats were associated with microsatellite instability (MSI). The tumors included: ten cases with no MSI, 14 cases with MSI = 1 locus, 13 cases with MSI = two loci and 13 cases with MSI > or = 3 loci. We investigated coding repeats within the TGF-beta RII, IGFIIR, BAX, hMSH6, hMSH3 and BRCA2 genes. The TGF-beta RII, IGFIIR, BAX, hMSH6 and hMSH3 repeats were altered in 11 (22%), five (10%), four (8%), 16 (32%) and five (10%) cases respectively. Mutations occurred only in MSI-positive (MSI+) tumors and correlated with increasing MSI levels. No alterations of the BRCA2 repeat were found. Mutations in genes other than hMSH6 were strongly associated to hMSH6 mutations, suggesting a key role of this gene. The non-coding BAT-26 and E-Cadherin 3' UTR poly(A)8/(T)15 repeats were analysed in 44 of the 50 cases. Novel tumor-associated alleles were observed only in MSI-positive GCs and were in most cases associated with mutations at coding repeats. Further investigations with BAT-40 confirmed that four cases manifested mononucleotide repeat alterations restricted to hMSH6 and one case to TGF-beta RII. A subset of tumors with MSI at two or more dinucleotide loci resulted negative for mutations at coding and non-coding mononucleotide repeats. |
| doi_str_mv | 10.1038/sj.onc.1201816 |
| format | Article |
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The tumors included: ten cases with no MSI, 14 cases with MSI = 1 locus, 13 cases with MSI = two loci and 13 cases with MSI > or = 3 loci. We investigated coding repeats within the TGF-beta RII, IGFIIR, BAX, hMSH6, hMSH3 and BRCA2 genes. The TGF-beta RII, IGFIIR, BAX, hMSH6 and hMSH3 repeats were altered in 11 (22%), five (10%), four (8%), 16 (32%) and five (10%) cases respectively. Mutations occurred only in MSI-positive (MSI+) tumors and correlated with increasing MSI levels. No alterations of the BRCA2 repeat were found. Mutations in genes other than hMSH6 were strongly associated to hMSH6 mutations, suggesting a key role of this gene. The non-coding BAT-26 and E-Cadherin 3' UTR poly(A)8/(T)15 repeats were analysed in 44 of the 50 cases. Novel tumor-associated alleles were observed only in MSI-positive GCs and were in most cases associated with mutations at coding repeats. Further investigations with BAT-40 confirmed that four cases manifested mononucleotide repeat alterations restricted to hMSH6 and one case to TGF-beta RII. A subset of tumors with MSI at two or more dinucleotide loci resulted negative for mutations at coding and non-coding mononucleotide repeats.</description><identifier>ISSN: 0950-9232</identifier><identifier>EISSN: 1476-5594</identifier><identifier>DOI: 10.1038/sj.onc.1201816</identifier><identifier>PMID: 9652743</identifier><language>eng</language><publisher>Basingstoke: Nature Publishing</publisher><subject>3' Untranslated regions ; Aged ; bcl-2-Associated X Protein ; Biological and medical sciences ; BRCA2 Protein ; Cadherins - genetics ; Carcinoma ; Cell physiology ; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes ; DNA, Neoplasm - analysis ; DNA-Binding Proteins - genetics ; E-cadherin ; Female ; Fundamental and applied biological sciences. Psychology ; Gastric cancer ; Humans ; Male ; Microsatellite instability ; Microsatellite Repeats ; Middle Aged ; Molecular and cellular biology ; Multidrug Resistance-Associated Proteins ; Mutation ; MutS Homolog 3 Protein ; Neoplasm Proteins - genetics ; Phenotype ; Phenotypes ; Protein-Serine-Threonine Kinases ; Proto-Oncogene Proteins - genetics ; Proto-Oncogene Proteins c-bcl-2 ; Receptor, IGF Type 2 - genetics ; Receptors, Transforming Growth Factor beta - genetics ; Stomach Neoplasms - genetics ; Transcription Factors - genetics ; Transforming growth factor-b ; Tumors</subject><ispartof>Oncogene, 1998-05, Vol.16 (21), p.2767-2772</ispartof><rights>1998 INIST-CNRS</rights><rights>Macmillan Publishers Limited 1998.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c447t-d0430252ecdc0f55645eadad4e21ec088b73cc108d2589733021a3f6d45f6f953</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,778,782,27907,27908</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2260824$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9652743$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>OTTINI, L</creatorcontrib><creatorcontrib>FALCHETTI, M</creatorcontrib><creatorcontrib>D'AMICO, C</creatorcontrib><creatorcontrib>AMOROSI, A</creatorcontrib><creatorcontrib>SAIEVA, C</creatorcontrib><creatorcontrib>MASALA, G</creatorcontrib><creatorcontrib>FRATI, L</creatorcontrib><creatorcontrib>CAMA, A</creatorcontrib><creatorcontrib>PALLI, D</creatorcontrib><creatorcontrib>MARIANI-COSTANTINI, R</creatorcontrib><title>Mutations at coding mononucleotide repeats in gastric cancer with the microsatellite mutator phenotype</title><title>Oncogene</title><addtitle>Oncogene</addtitle><description>We analysed 50 gastric carcinomas (GCs) to verify whether mutations at coding repeats were associated with microsatellite instability (MSI). The tumors included: ten cases with no MSI, 14 cases with MSI = 1 locus, 13 cases with MSI = two loci and 13 cases with MSI > or = 3 loci. We investigated coding repeats within the TGF-beta RII, IGFIIR, BAX, hMSH6, hMSH3 and BRCA2 genes. The TGF-beta RII, IGFIIR, BAX, hMSH6 and hMSH3 repeats were altered in 11 (22%), five (10%), four (8%), 16 (32%) and five (10%) cases respectively. Mutations occurred only in MSI-positive (MSI+) tumors and correlated with increasing MSI levels. No alterations of the BRCA2 repeat were found. Mutations in genes other than hMSH6 were strongly associated to hMSH6 mutations, suggesting a key role of this gene. The non-coding BAT-26 and E-Cadherin 3' UTR poly(A)8/(T)15 repeats were analysed in 44 of the 50 cases. Novel tumor-associated alleles were observed only in MSI-positive GCs and were in most cases associated with mutations at coding repeats. Further investigations with BAT-40 confirmed that four cases manifested mononucleotide repeat alterations restricted to hMSH6 and one case to TGF-beta RII. A subset of tumors with MSI at two or more dinucleotide loci resulted negative for mutations at coding and non-coding mononucleotide repeats.</description><subject>3' Untranslated regions</subject><subject>Aged</subject><subject>bcl-2-Associated X Protein</subject><subject>Biological and medical sciences</subject><subject>BRCA2 Protein</subject><subject>Cadherins - genetics</subject><subject>Carcinoma</subject><subject>Cell physiology</subject><subject>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</subject><subject>DNA, Neoplasm - analysis</subject><subject>DNA-Binding Proteins - genetics</subject><subject>E-cadherin</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gastric cancer</subject><subject>Humans</subject><subject>Male</subject><subject>Microsatellite instability</subject><subject>Microsatellite Repeats</subject><subject>Middle Aged</subject><subject>Molecular and cellular biology</subject><subject>Multidrug Resistance-Associated Proteins</subject><subject>Mutation</subject><subject>MutS Homolog 3 Protein</subject><subject>Neoplasm Proteins - genetics</subject><subject>Phenotype</subject><subject>Phenotypes</subject><subject>Protein-Serine-Threonine Kinases</subject><subject>Proto-Oncogene Proteins - genetics</subject><subject>Proto-Oncogene Proteins c-bcl-2</subject><subject>Receptor, IGF Type 2 - genetics</subject><subject>Receptors, Transforming Growth Factor beta - genetics</subject><subject>Stomach Neoplasms - genetics</subject><subject>Transcription Factors - genetics</subject><subject>Transforming growth factor-b</subject><subject>Tumors</subject><issn>0950-9232</issn><issn>1476-5594</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkctrFTEUxkNR6m11250QsLiba96PpRRrhYobXYc0yfTmMpOMSQbpf28uHbpw4-pwOL_znccHwBVGe4yo-lSP-5zcHhOEFRZnYIeZFAPnmr0CO6Q5GjSh5A24qPWIEJIakXNwrgUnktEdGL-vzbaYU4W2QZd9TI9wzimn1U0ht-gDLGEJtlUYE3y0tZXooLPJhQL_xHaA7RDgHF3J1bYwTbH19CSaC1wOIeX2tIS34PVopxrebfES_Lr98vPmbrj_8fXbzef7wTEm2-ARo4hwEpx3aORcMB6st54FgoNDSj1I6hxGyhOutKQdxpaOwjM-ilFzegk-PusuJf9eQ21mjtX1rWwKea1Gai0lVuy_IBaMaqZwBz_8Ax7zWlI_whDBMOly_DR3_0yd3lBLGM1S4mzLk8HInHwy9Wi6T2bzqTe832TXhzn4F3wzptevt7qtzk5j6Q-P9QUjRCBFGP0Lc9-cnA</recordid><startdate>19980528</startdate><enddate>19980528</enddate><creator>OTTINI, L</creator><creator>FALCHETTI, M</creator><creator>D'AMICO, C</creator><creator>AMOROSI, A</creator><creator>SAIEVA, C</creator><creator>MASALA, G</creator><creator>FRATI, L</creator><creator>CAMA, A</creator><creator>PALLI, D</creator><creator>MARIANI-COSTANTINI, R</creator><general>Nature Publishing</general><general>Nature Publishing Group</general><scope>IQODW</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>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>19980528</creationdate><title>Mutations at coding mononucleotide repeats in gastric cancer with the microsatellite mutator phenotype</title><author>OTTINI, L ; FALCHETTI, M ; D'AMICO, C ; AMOROSI, A ; SAIEVA, C ; MASALA, G ; FRATI, L ; CAMA, A ; PALLI, D ; MARIANI-COSTANTINI, R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c447t-d0430252ecdc0f55645eadad4e21ec088b73cc108d2589733021a3f6d45f6f953</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>3' Untranslated regions</topic><topic>Aged</topic><topic>bcl-2-Associated X Protein</topic><topic>Biological and medical sciences</topic><topic>BRCA2 Protein</topic><topic>Cadherins - genetics</topic><topic>Carcinoma</topic><topic>Cell physiology</topic><topic>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</topic><topic>DNA, Neoplasm - analysis</topic><topic>DNA-Binding Proteins - genetics</topic><topic>E-cadherin</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gastric cancer</topic><topic>Humans</topic><topic>Male</topic><topic>Microsatellite instability</topic><topic>Microsatellite Repeats</topic><topic>Middle Aged</topic><topic>Molecular and cellular biology</topic><topic>Multidrug Resistance-Associated Proteins</topic><topic>Mutation</topic><topic>MutS Homolog 3 Protein</topic><topic>Neoplasm Proteins - genetics</topic><topic>Phenotype</topic><topic>Phenotypes</topic><topic>Protein-Serine-Threonine Kinases</topic><topic>Proto-Oncogene Proteins - genetics</topic><topic>Proto-Oncogene Proteins c-bcl-2</topic><topic>Receptor, IGF Type 2 - genetics</topic><topic>Receptors, Transforming Growth Factor beta - genetics</topic><topic>Stomach Neoplasms - genetics</topic><topic>Transcription Factors - genetics</topic><topic>Transforming growth factor-b</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>OTTINI, L</creatorcontrib><creatorcontrib>FALCHETTI, M</creatorcontrib><creatorcontrib>D'AMICO, C</creatorcontrib><creatorcontrib>AMOROSI, A</creatorcontrib><creatorcontrib>SAIEVA, C</creatorcontrib><creatorcontrib>MASALA, G</creatorcontrib><creatorcontrib>FRATI, L</creatorcontrib><creatorcontrib>CAMA, A</creatorcontrib><creatorcontrib>PALLI, D</creatorcontrib><creatorcontrib>MARIANI-COSTANTINI, R</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>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</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>OTTINI, L</au><au>FALCHETTI, M</au><au>D'AMICO, C</au><au>AMOROSI, A</au><au>SAIEVA, C</au><au>MASALA, G</au><au>FRATI, L</au><au>CAMA, A</au><au>PALLI, D</au><au>MARIANI-COSTANTINI, R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mutations at coding mononucleotide repeats in gastric cancer with the microsatellite mutator phenotype</atitle><jtitle>Oncogene</jtitle><addtitle>Oncogene</addtitle><date>1998-05-28</date><risdate>1998</risdate><volume>16</volume><issue>21</issue><spage>2767</spage><epage>2772</epage><pages>2767-2772</pages><issn>0950-9232</issn><eissn>1476-5594</eissn><abstract>We analysed 50 gastric carcinomas (GCs) to verify whether mutations at coding repeats were associated with microsatellite instability (MSI). The tumors included: ten cases with no MSI, 14 cases with MSI = 1 locus, 13 cases with MSI = two loci and 13 cases with MSI > or = 3 loci. We investigated coding repeats within the TGF-beta RII, IGFIIR, BAX, hMSH6, hMSH3 and BRCA2 genes. The TGF-beta RII, IGFIIR, BAX, hMSH6 and hMSH3 repeats were altered in 11 (22%), five (10%), four (8%), 16 (32%) and five (10%) cases respectively. Mutations occurred only in MSI-positive (MSI+) tumors and correlated with increasing MSI levels. No alterations of the BRCA2 repeat were found. Mutations in genes other than hMSH6 were strongly associated to hMSH6 mutations, suggesting a key role of this gene. The non-coding BAT-26 and E-Cadherin 3' UTR poly(A)8/(T)15 repeats were analysed in 44 of the 50 cases. Novel tumor-associated alleles were observed only in MSI-positive GCs and were in most cases associated with mutations at coding repeats. Further investigations with BAT-40 confirmed that four cases manifested mononucleotide repeat alterations restricted to hMSH6 and one case to TGF-beta RII. A subset of tumors with MSI at two or more dinucleotide loci resulted negative for mutations at coding and non-coding mononucleotide repeats.</abstract><cop>Basingstoke</cop><pub>Nature Publishing</pub><pmid>9652743</pmid><doi>10.1038/sj.onc.1201816</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Nature; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Springer Nature - Complete Springer Journals |
| subjects | 3' Untranslated regions Aged bcl-2-Associated X Protein Biological and medical sciences BRCA2 Protein Cadherins - genetics Carcinoma Cell physiology Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes DNA, Neoplasm - analysis DNA-Binding Proteins - genetics E-cadherin Female Fundamental and applied biological sciences. Psychology Gastric cancer Humans Male Microsatellite instability Microsatellite Repeats Middle Aged Molecular and cellular biology Multidrug Resistance-Associated Proteins Mutation MutS Homolog 3 Protein Neoplasm Proteins - genetics Phenotype Phenotypes Protein-Serine-Threonine Kinases Proto-Oncogene Proteins - genetics Proto-Oncogene Proteins c-bcl-2 Receptor, IGF Type 2 - genetics Receptors, Transforming Growth Factor beta - genetics Stomach Neoplasms - genetics Transcription Factors - genetics Transforming growth factor-b Tumors |
| title | Mutations at coding mononucleotide repeats in gastric cancer with the microsatellite mutator phenotype |
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