{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:38:01Z","timestamp":1791347881255,"version":"4.3.1"},"reference-count":45,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2014,9,11]],"date-time":"2014-09-11T00:00:00Z","timestamp":1410393600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"University Hospital Heidelberg"},{"name":"The European Molecular Biology Laboratory"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:sec><jats:label\/><jats:p>Different DNA mismatch repair (MMR)\u2010deficient mouse strains have been developed as models for the inherited cancer predisposing Lynch syndrome. It is completely unresolved, whether coding mononucleotide repeat (cMNR) gene mutations in these mice can contribute to intestinal tumorigenesis and whether MMR\u2010deficient mice are a suitable molecular model of human microsatellite instability (MSI)\u2010associated intestinal tumorigenesis. A proof\u2010of\u2010principle study was performed to identify mouse cMNR\u2010harboring genes affected by insertion\/deletion mutations in MSI murine intestinal tumors. Bioinformatic algorithms were developed to establish a database of mouse cMNR\u2010harboring genes. A panel of five mouse noncoding mononucleotide markers was used for MSI classification of intestinal matched normal\/tumor tissues from MMR\u2010deficient (<jats:italic>Mlh1<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup><jats:italic>, Msh2<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup><jats:italic>, Msh2<\/jats:italic><jats:sup><jats:italic>LoxP\/LoxP<\/jats:italic><\/jats:sup>) mice. cMNR frameshift mutations of candidate genes were determined by DNA fragment analysis. Murine MSI intestinal tumors but not normal tissues from MMR\u2010deficient mice showed cMNR frameshift mutations in six candidate genes (<jats:italic>Elavl3<\/jats:italic>, <jats:italic>Tmem107<\/jats:italic>, <jats:italic>Glis2<\/jats:italic>, <jats:italic>Sdccag1, Senp6, Rfc3<\/jats:italic>). cMNRs of mouse <jats:italic>Rfc3<\/jats:italic> and <jats:italic>Elavl3<\/jats:italic> are conserved in type and length in their human orthologs that are known to be mutated in human MSI colorectal, endometrial and gastric cancer. We provide evidence for the utility of a mononucleotide marker panel for detection of MSI in murine tumors, the existence of cMNR instability in MSI murine tumors, the utility of mouse subspecies DNA for identification of polymorphic repeats, and repeat conservation among some orthologous human\/mouse genes, two of them showing instability in human and mouse MSI intestinal tumors. MMR\u2010deficient mice hence are a useful molecular model system for analyzing MSI intestinal carcinogenesis. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mc.22213","type":"journal-article","created":{"date-parts":[[2014,9,11]],"date-time":"2014-09-11T16:13:40Z","timestamp":1410452020000},"page":"1376-1386","source":"Crossref","is-referenced-by-count":34,"title":["Detection of coding microsatellite frameshift mutations in DNA mismatch repair\u2010deficient mouse intestinal tumors"],"prefix":"10.1002","volume":"54","author":[{"given":"Stefan M.","family":"Woerner","sequence":"first","affiliation":[{"name":"Department of Applied Tumor Biology Institute of Pathology University Hospital Heidelberg Heidelberg Germany"},{"name":"Molecular Medicine Partnership Unit University of Heidelberg and European Molecular Biology Laboratory Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Tosti","sequence":"additional","affiliation":[{"name":"Department of Cell Biology Albert Einstein College of Medicine New York NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan P.","family":"Yuan","sequence":"additional","affiliation":[{"name":"Structural and Computational Biology Unit European Molecular Biology Laboratory Heidelberg Germany"},{"name":"Molecular Medicine Partnership Unit University of Heidelberg and European Molecular Biology Laboratory Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Kloor","sequence":"additional","affiliation":[{"name":"Department of Applied Tumor Biology Institute of Pathology University Hospital Heidelberg Heidelberg Germany"},{"name":"Molecular Medicine Partnership Unit University of Heidelberg and European Molecular Biology Laboratory Heidelberg Germany"},{"name":"Clinical Cooperation Unit Applied Tumor Biology DKFZ Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peer","family":"Bork","sequence":"additional","affiliation":[{"name":"Structural and Computational Biology Unit European Molecular Biology Laboratory Heidelberg Germany"},{"name":"Molecular Medicine Partnership Unit University of Heidelberg and European Molecular Biology Laboratory Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winfried","family":"Edelmann","sequence":"additional","affiliation":[{"name":"Department of Cell Biology Albert Einstein College of Medicine New York NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Gebert","sequence":"additional","affiliation":[{"name":"Department of Applied Tumor Biology Institute of Pathology University Hospital Heidelberg Heidelberg Germany"},{"name":"Molecular Medicine Partnership Unit University of Heidelberg and European Molecular Biology Laboratory Heidelberg Germany"},{"name":"Clinical Cooperation Unit Applied Tumor Biology DKFZ Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,9,11]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R600022200"},{"key":"e_1_2_7_3_1","first-page":"2029","article-title":"Methylation of CpG in a small region of the hMLH1 promoter invariably correlates with the absence of gene expression","volume":"59","author":"Deng G","year":"1999","journal-title":"Cancer Res"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90546-3"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90330-S"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/368258a0"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8128251"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.12.064"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.20511"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.190210897"},{"key":"e_1_2_7_11_1","first-page":"994","article-title":"Evidence of selection for clones having genetic inactivation of the activin A type II receptor (ACVR2) gene in gastrointestinal cancers","volume":"63","author":"Hempen PM","year":"2003","journal-title":"Cancer Res"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.30021"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0995-64"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0796-336"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0398-276"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90319-4"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81312-4"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-03-2957"},{"key":"e_1_2_7_19_1","first-page":"803","article-title":"The DNA mismatch repair genes Msh3 and Msh6 cooperate in intestinal tumor suppression","volume":"60","author":"Edelmann W","year":"2000","journal-title":"Cancer Res"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1060603"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80433-X"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2004.06.024"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/21.7.1291"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.190.3.323"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20080789"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.7.3122"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.12.6850"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.11.009"},{"key":"e_1_2_7_29_1","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.1182\/blood.V95.5.1767.005k07_1767_1772","article-title":"MSH2\u2010deficient murine lymphomas harbor insertion\/deletion mutations in the transforming growth factor beta receptor type 2 gene and display low not high frequency microsatellite instability","volume":"95","author":"Lowsky R","year":"2000","journal-title":"Blood"},{"key":"e_1_2_7_30_1","first-page":"1301","article-title":"Tumorigenesis in Mlh1 and Mlh1\/Apc1638N mutant mice","volume":"59","author":"Edelmann W","year":"1999","journal-title":"Cancer Res"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/mc.10157"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/mc.20146"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.1299"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1206421"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkp839"},{"key":"e_1_2_7_36_1","first-page":"5248","article-title":"A National Cancer Institute Workshop on microsatellite instability for cancer detection and familial predisposition: Development of international criteria for the determination of microsatellite instability in colorectal cancer","volume":"58","author":"Boland CR","year":"1998","journal-title":"Cancer Res"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.02.7227"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.2800"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-394622-5.00007-9"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(19980529)76:5<652::AID-IJC7>3.0.CO;2-P"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1208962"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.1197"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E10-06-0504"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.9.16.12619"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-11-1431"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2010.03.006"}],"container-title":["Molecular Carcinogenesis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmc.22213","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mc.22213","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T17:10:52Z","timestamp":1696353052000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mc.22213"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,9,11]]},"references-count":45,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2015,11]]}},"alternative-id":["10.1002\/mc.22213"],"URL":"https:\/\/doi.org\/10.1002\/mc.22213","archive":["Portico"],"relation":{},"ISSN":["0899-1987","1098-2744"],"issn-type":[{"value":"0899-1987","type":"print"},{"value":"1098-2744","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,9,11]]}}}