Bias in detection of instability of the (C)8 mononucleotide repeat of MSH6 in tumours from HNPCC patients
Recently, we and others reported instability in the (C)8 repeat in exon 5 of MSH6 as a preferential target for somatic mutations in tumours from MSH6 germline mutation carriers. Here, we report that in 45% of tumours from MLH1, MSH2 and MSH6 germline mutation carriers no sequence change in the (C)8...
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| Veröffentlicht in: | Oncogene 2001-09, Vol.20 (43), p.6241-6244 |
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| creator | DE LEEUW, Wiljo J. F VAN PUIJENBROEK, Marjo MERX, Renee WIJNEN, Juul Th BRÖCKER-VRIENDS, Annette H. J. T TOPS, Carli VASEN, Hans CORNELISSE, Cees J MORREAU, Hans |
| description | Recently, we and others reported instability in the (C)8 repeat in exon 5 of MSH6 as a preferential target for somatic mutations in tumours from MSH6 germline mutation carriers. Here, we report that in 45% of tumours from MLH1, MSH2 and MSH6 germline mutation carriers no sequence change in the (C)8 repeat of MSH6 was found upon DNA sequencing analysis of PCR products with a shift in electrophoresis mobility. Using "standard" PCR primers a high frequency of instability (50-86%) of the (C)8 repeat was found, but using a modified PCR reverse primer, accomplishing modulation of non-templated addition of adenine during in vitro PCR amplification by the Taq polymerase, a markedly lower frequency of instability was found in tumours from MLH1, MSH2 and MSH6 mutation carriers (6, 13 and 40%, respectively). Furthermore, a significant difference of the frequency of instability of the (C)8 repeat in tumours from MSH6 mutation carriers was found compared to MLH1, MSH2 mutation carriers. These results might have important implications for the detection of instability of other short mononucleotide repeats, e.g. TGFbetaRII, BAX, IGFRII, PTEN, BRCA2. |
| doi_str_mv | 10.1038/sj.onc.1204795 |
| format | Article |
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F ; VAN PUIJENBROEK, Marjo ; MERX, Renee ; WIJNEN, Juul Th ; BRÖCKER-VRIENDS, Annette H. J. T ; TOPS, Carli ; VASEN, Hans ; CORNELISSE, Cees J ; MORREAU, Hans</creator><creatorcontrib>DE LEEUW, Wiljo J. F ; VAN PUIJENBROEK, Marjo ; MERX, Renee ; WIJNEN, Juul Th ; BRÖCKER-VRIENDS, Annette H. J. T ; TOPS, Carli ; VASEN, Hans ; CORNELISSE, Cees J ; MORREAU, Hans</creatorcontrib><description>Recently, we and others reported instability in the (C)8 repeat in exon 5 of MSH6 as a preferential target for somatic mutations in tumours from MSH6 germline mutation carriers. Here, we report that in 45% of tumours from MLH1, MSH2 and MSH6 germline mutation carriers no sequence change in the (C)8 repeat of MSH6 was found upon DNA sequencing analysis of PCR products with a shift in electrophoresis mobility. Using "standard" PCR primers a high frequency of instability (50-86%) of the (C)8 repeat was found, but using a modified PCR reverse primer, accomplishing modulation of non-templated addition of adenine during in vitro PCR amplification by the Taq polymerase, a markedly lower frequency of instability was found in tumours from MLH1, MSH2 and MSH6 mutation carriers (6, 13 and 40%, respectively). Furthermore, a significant difference of the frequency of instability of the (C)8 repeat in tumours from MSH6 mutation carriers was found compared to MLH1, MSH2 mutation carriers. These results might have important implications for the detection of instability of other short mononucleotide repeats, e.g. TGFbetaRII, BAX, IGFRII, PTEN, BRCA2.</description><identifier>ISSN: 0950-9232</identifier><identifier>EISSN: 1476-5594</identifier><identifier>DOI: 10.1038/sj.onc.1204795</identifier><identifier>PMID: 11593433</identifier><identifier>CODEN: ONCNES</identifier><language>eng</language><publisher>Basingstoke: Nature Publishing</publisher><subject>Adaptor Proteins, Signal Transducing ; Adenine ; Bias ; Biological and medical sciences ; BRCA2 protein ; Carrier Proteins ; Cell physiology ; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes ; Colorectal cancer ; DNA Mutational Analysis ; DNA Primers - metabolism ; DNA sequencing ; DNA-Binding Proteins ; Electrophoretic mobility ; Exons ; Fundamental and applied biological sciences. Psychology ; Fungal Proteins - genetics ; Gene Deletion ; Genetic disorders ; Humans ; Microsatellite Repeats ; MLH1 gene ; MLH1 protein ; Molecular and cellular biology ; MSH2 gene ; MSH2 protein ; MSH6 gene ; MSH6 protein ; Mutation ; MutL Protein Homolog 1 ; MutS Homolog 2 Protein ; Neoplasm Proteins - genetics ; Nuclear Proteins ; Polymerase Chain Reaction ; Proto-Oncogene Proteins - genetics ; PTEN protein ; Reproducibility of Results ; Saccharomyces cerevisiae Proteins ; Sensitivity and Specificity ; Sequence analysis ; Taq protein ; Trinucleotide Repeat Expansion ; Tumors</subject><ispartof>Oncogene, 2001-09, Vol.20 (43), p.6241-6244</ispartof><rights>2002 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Sep 27, 2001</rights><rights>Macmillan Publishers Limited 2001.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c407t-6b3e650376dc7bc2f5c34c99d1a794e74edb0380ac488fe23e14d848fd95149d3</citedby><cites>FETCH-LOGICAL-c407t-6b3e650376dc7bc2f5c34c99d1a794e74edb0380ac488fe23e14d848fd95149d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14154354$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11593433$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>DE LEEUW, Wiljo J. F</creatorcontrib><creatorcontrib>VAN PUIJENBROEK, Marjo</creatorcontrib><creatorcontrib>MERX, Renee</creatorcontrib><creatorcontrib>WIJNEN, Juul Th</creatorcontrib><creatorcontrib>BRÖCKER-VRIENDS, Annette H. J. T</creatorcontrib><creatorcontrib>TOPS, Carli</creatorcontrib><creatorcontrib>VASEN, Hans</creatorcontrib><creatorcontrib>CORNELISSE, Cees J</creatorcontrib><creatorcontrib>MORREAU, Hans</creatorcontrib><title>Bias in detection of instability of the (C)8 mononucleotide repeat of MSH6 in tumours from HNPCC patients</title><title>Oncogene</title><addtitle>Oncogene</addtitle><description>Recently, we and others reported instability in the (C)8 repeat in exon 5 of MSH6 as a preferential target for somatic mutations in tumours from MSH6 germline mutation carriers. Here, we report that in 45% of tumours from MLH1, MSH2 and MSH6 germline mutation carriers no sequence change in the (C)8 repeat of MSH6 was found upon DNA sequencing analysis of PCR products with a shift in electrophoresis mobility. Using "standard" PCR primers a high frequency of instability (50-86%) of the (C)8 repeat was found, but using a modified PCR reverse primer, accomplishing modulation of non-templated addition of adenine during in vitro PCR amplification by the Taq polymerase, a markedly lower frequency of instability was found in tumours from MLH1, MSH2 and MSH6 mutation carriers (6, 13 and 40%, respectively). Furthermore, a significant difference of the frequency of instability of the (C)8 repeat in tumours from MSH6 mutation carriers was found compared to MLH1, MSH2 mutation carriers. These results might have important implications for the detection of instability of other short mononucleotide repeats, e.g. TGFbetaRII, BAX, IGFRII, PTEN, BRCA2.</description><subject>Adaptor Proteins, Signal Transducing</subject><subject>Adenine</subject><subject>Bias</subject><subject>Biological and medical sciences</subject><subject>BRCA2 protein</subject><subject>Carrier Proteins</subject><subject>Cell physiology</subject><subject>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</subject><subject>Colorectal cancer</subject><subject>DNA Mutational Analysis</subject><subject>DNA Primers - metabolism</subject><subject>DNA sequencing</subject><subject>DNA-Binding Proteins</subject><subject>Electrophoretic mobility</subject><subject>Exons</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fungal Proteins - genetics</subject><subject>Gene Deletion</subject><subject>Genetic disorders</subject><subject>Humans</subject><subject>Microsatellite Repeats</subject><subject>MLH1 gene</subject><subject>MLH1 protein</subject><subject>Molecular and cellular biology</subject><subject>MSH2 gene</subject><subject>MSH2 protein</subject><subject>MSH6 gene</subject><subject>MSH6 protein</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>Polymerase Chain Reaction</subject><subject>Proto-Oncogene Proteins - genetics</subject><subject>PTEN protein</subject><subject>Reproducibility of Results</subject><subject>Saccharomyces cerevisiae Proteins</subject><subject>Sensitivity and Specificity</subject><subject>Sequence analysis</subject><subject>Taq protein</subject><subject>Trinucleotide Repeat Expansion</subject><subject>Tumors</subject><issn>0950-9232</issn><issn>1476-5594</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</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>eNqF0U2L1TAUBuAginMd3bqUoCjOotecJG2apRadOzB-gLouaXqKubTNnSRdzL83ZQoDggwEwoEnJ7y8hLwEtgcm6g_xuPez3QNnUunyEdmBVFVRllo-JjumS1ZoLvgZeRbjkTGmNONPyRlAqYUUYkfcJ2cidTPtMaFNzs_UD3mOyXRudOl2HdMfpO-bi5pOfvbzYkf0yfVIA57QpFV8_Xmo1i1pmfwSIh2Cn-jh24-moSeTHM4pPidPBjNGfLHd5-T3l8-_mkNx_f3yqvl4XVjJVCqqTmBVMqGq3qrO8qG0QlqtezBKS1QS-y4HZ8bKuh6QCwTZ17Ieel2C1L04J-_u9p6Cv1kwpnZy0eI4mhn9ElvFIXNRPQihBg3AVvjmH3jMIeccouWVBAG8rlRWr_-ruBL5U4CM9nfIBh9jwKE9BTeZcNsCa9dC23hsc6HtVmh-8GrbunQT9vd8azCDtxsw0ZpxCGa2Lt47CaUU-fwF8JKm2g</recordid><startdate>20010927</startdate><enddate>20010927</enddate><creator>DE LEEUW, Wiljo J. 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F ; VAN PUIJENBROEK, Marjo ; MERX, Renee ; WIJNEN, Juul Th ; BRÖCKER-VRIENDS, Annette H. J. T ; TOPS, Carli ; VASEN, Hans ; CORNELISSE, Cees J ; MORREAU, Hans</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c407t-6b3e650376dc7bc2f5c34c99d1a794e74edb0380ac488fe23e14d848fd95149d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Adaptor Proteins, Signal Transducing</topic><topic>Adenine</topic><topic>Bias</topic><topic>Biological and medical sciences</topic><topic>BRCA2 protein</topic><topic>Carrier Proteins</topic><topic>Cell physiology</topic><topic>Cell transformation and carcinogenesis. 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Psychology</topic><topic>Fungal Proteins - genetics</topic><topic>Gene Deletion</topic><topic>Genetic disorders</topic><topic>Humans</topic><topic>Microsatellite Repeats</topic><topic>MLH1 gene</topic><topic>MLH1 protein</topic><topic>Molecular and cellular biology</topic><topic>MSH2 gene</topic><topic>MSH2 protein</topic><topic>MSH6 gene</topic><topic>MSH6 protein</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>Polymerase Chain Reaction</topic><topic>Proto-Oncogene Proteins - genetics</topic><topic>PTEN protein</topic><topic>Reproducibility of Results</topic><topic>Saccharomyces cerevisiae Proteins</topic><topic>Sensitivity and Specificity</topic><topic>Sequence analysis</topic><topic>Taq protein</topic><topic>Trinucleotide Repeat Expansion</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>DE LEEUW, Wiljo J. 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F</au><au>VAN PUIJENBROEK, Marjo</au><au>MERX, Renee</au><au>WIJNEN, Juul Th</au><au>BRÖCKER-VRIENDS, Annette H. J. T</au><au>TOPS, Carli</au><au>VASEN, Hans</au><au>CORNELISSE, Cees J</au><au>MORREAU, Hans</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Bias in detection of instability of the (C)8 mononucleotide repeat of MSH6 in tumours from HNPCC patients</atitle><jtitle>Oncogene</jtitle><addtitle>Oncogene</addtitle><date>2001-09-27</date><risdate>2001</risdate><volume>20</volume><issue>43</issue><spage>6241</spage><epage>6244</epage><pages>6241-6244</pages><issn>0950-9232</issn><eissn>1476-5594</eissn><coden>ONCNES</coden><abstract>Recently, we and others reported instability in the (C)8 repeat in exon 5 of MSH6 as a preferential target for somatic mutations in tumours from MSH6 germline mutation carriers. Here, we report that in 45% of tumours from MLH1, MSH2 and MSH6 germline mutation carriers no sequence change in the (C)8 repeat of MSH6 was found upon DNA sequencing analysis of PCR products with a shift in electrophoresis mobility. Using "standard" PCR primers a high frequency of instability (50-86%) of the (C)8 repeat was found, but using a modified PCR reverse primer, accomplishing modulation of non-templated addition of adenine during in vitro PCR amplification by the Taq polymerase, a markedly lower frequency of instability was found in tumours from MLH1, MSH2 and MSH6 mutation carriers (6, 13 and 40%, respectively). Furthermore, a significant difference of the frequency of instability of the (C)8 repeat in tumours from MSH6 mutation carriers was found compared to MLH1, MSH2 mutation carriers. These results might have important implications for the detection of instability of other short mononucleotide repeats, e.g. TGFbetaRII, BAX, IGFRII, PTEN, BRCA2.</abstract><cop>Basingstoke</cop><pub>Nature Publishing</pub><pmid>11593433</pmid><doi>10.1038/sj.onc.1204795</doi><tpages>4</tpages></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Springer Nature - Complete Springer Journals; Nature Journals Online |
| subjects | Adaptor Proteins, Signal Transducing Adenine Bias Biological and medical sciences BRCA2 protein Carrier Proteins Cell physiology Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes Colorectal cancer DNA Mutational Analysis DNA Primers - metabolism DNA sequencing DNA-Binding Proteins Electrophoretic mobility Exons Fundamental and applied biological sciences. Psychology Fungal Proteins - genetics Gene Deletion Genetic disorders Humans Microsatellite Repeats MLH1 gene MLH1 protein Molecular and cellular biology MSH2 gene MSH2 protein MSH6 gene MSH6 protein Mutation MutL Protein Homolog 1 MutS Homolog 2 Protein Neoplasm Proteins - genetics Nuclear Proteins Polymerase Chain Reaction Proto-Oncogene Proteins - genetics PTEN protein Reproducibility of Results Saccharomyces cerevisiae Proteins Sensitivity and Specificity Sequence analysis Taq protein Trinucleotide Repeat Expansion Tumors |
| title | Bias in detection of instability of the (C)8 mononucleotide repeat of MSH6 in tumours from HNPCC patients |
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