{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:22:20Z","timestamp":1790400140813,"version":"4.1.0"},"reference-count":26,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2002,12,6]],"date-time":"2002-12-06T00:00:00Z","timestamp":1039132800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2003,2,20]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hereditary nonpolyposis colorectal cancer (HNPCC) is often caused by a deficiency in DNA mismatch repair. By using conventional methods of mutation analysis, point mutations in the DNA mismatch repair genes <jats:italic>MSH2<\/jats:italic> and <jats:italic>MLH1<\/jats:italic> have been detected in up to 64% of patients suspected of HNPCC. However, large genomic deletions cannot be detected by these methods. In our study, we applied a semiquantitative multiplex PCR to detect the proportion of large deletions in patients meeting the Bethesda criteria whose tumours exhibited microsatellite instability (MSI). Of 368 unrelated patients, 180 exhibited MSI. In these patients, 68 disease\u2010causing point mutations (38%) had previously been detected in the <jats:italic>MSH2<\/jats:italic> and <jats:italic>MLH1<\/jats:italic> genes by SSCP, heteroduplex analysis or DHPLC followed by direct sequencing. The remaining 112 patients (including 24 patients with rare missense or other unclarified variants) were examined for large deletions. We identified deletions in 19 patients (10.6%); 11\/19 (58%) deletions were located in <jats:italic>MSH2<\/jats:italic> and 8\/19 (42%) in <jats:italic>MLH1<\/jats:italic>, respectively. The size of deletions ranged from 1 exon to a deletion of a whole gene. Five breakpoints of deletions were sequenced; Alu\u2010repetitive elements were involved in all of them. In patients meeting the Amsterdam criteria the proportion of large deletions was 12.6%. A similar proportion of deletions was found in the group of patients with a positive family history for colorectal cancer and MSI tumours, not meeting the Amsterdam criteria. The results of our study suggest that large genomic deletions in both <jats:italic>MSH2<\/jats:italic> and <jats:italic>MLH1<\/jats:italic> genes play a considerable role in the pathogenesis of HNPCC and should be part of the routine HNPCC mutation detection protocols. \u00a9 2002 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.10869","type":"journal-article","created":{"date-parts":[[2002,12,20]],"date-time":"2002-12-20T14:08:24Z","timestamp":1040393304000},"page":"636-641","source":"Crossref","is-referenced-by-count":80,"title":["Hereditary nonpolyposis colorectal cancer: Frequent occurrence of large genomic deletions in <i>MSH2<\/i> and <i>MLH1<\/i> genes"],"prefix":"10.1002","volume":"103","author":[{"given":"Yaping","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waltraut","family":"Friedl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christof","family":"Lamberti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Jungck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micaela","family":"Mathiak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constanze","family":"Pagenstecher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Propping","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Mangold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2002,12,6]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1568-7864(02)00081-2"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(99)70510-X"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02053699"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/89.23.1758"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.7.735"},{"key":"e_1_2_6_7_2","first-page":"7798","article-title":"The 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