{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:27:40Z","timestamp":1781108860530,"version":"3.54.1"},"reference-count":38,"publisher":"National Academy of Sciences","issue":"15","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1998,7,21]]},"abstract":"<jats:p>\n                    DNA mismatch repair (MMR) deficiency is associated with an increased mutational burden and predisposition to certain malignancies. Relatively little is known, however, about gene-specific mutation frequencies within MMR-deficient primary tumors. Thymic lymphomas from\n                    <jats:italic>Msh2<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice were thus analyzed by using a\n                    <jats:italic>lacI<\/jats:italic>\n                    -based transgenic shuttle-phage mutation detection system. All tumors exhibited greatly elevated\n                    <jats:italic>lacI<\/jats:italic>\n                    gene mutation frequencies, ranging from 3.2- to 17.4-fold above the \u224815-fold elevations present within normal\n                    <jats:italic>Msh2<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    thymi. In addition,\n                    <jats:italic>lacI<\/jats:italic>\n                    genes harboring multiple changes, including clusters of mutations, were found in thymic tumor DNA. The results suggest that an additional mutator activity, such as an error-prone DNA polymerase, leads to increased genomic instability in these MMR-deficient tumors.\n                  <\/jats:p>","DOI":"10.1073\/pnas.95.15.8739","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:35:50Z","timestamp":1027679750000},"page":"8739-8743","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":31,"title":["Tumors of DNA mismatch repair-deficient hosts exhibit dramatic increases in genomic instability"],"prefix":"10.1073","volume":"95","author":[{"given":"Agnes","family":"Baross-Francis","sequence":"first","affiliation":[{"name":"Center for Molecular Medicine and Therapeutics, and Department of Medicine, University of British Columbia, Vancouver, BC Canada V5Z 4H4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan E.","family":"Andrew","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine and Therapeutics, and Department of Medicine, University of British Columbia, Vancouver, BC Canada V5Z 4H4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janice E.","family":"Penney","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine and Therapeutics, and Department of Medicine, University of British Columbia, Vancouver, BC Canada V5Z 4H4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank R.","family":"Jirik","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine and Therapeutics, and Department of Medicine, University of British Columbia, Vancouver, BC Canada V5Z 4H4"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1998,7,21]]},"reference":[{"key":"e_1_3_2_1_2","first-page":"3075","volume":"51","author":"Loeb L A","year":"1991","unstructured":"L A Loeb Cancer Res 51, 3075\u20133079 (1991).","journal-title":"Cancer Res"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0027-5107(95)00117-4"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81333-1"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1006\/scbi.1996.0032"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0995-64"},{"key":"e_1_3_2_6_2","first-page":"2922","volume":"56","author":"Reitmair A H","year":"1996","unstructured":"A H Reitmair, J C Cai, M Bjerknes, M Redston, H Cheng, M T L Pind, K Hay, A Mitri, B V Bapat, T W Mak, et al. 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