{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T22:20:17Z","timestamp":1781907617016,"version":"3.54.5"},"reference-count":42,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2002,1,31]],"date-time":"2002-01-31T00:00:00Z","timestamp":1012435200000},"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":[[2002,4,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>HNPCC is an autosomal dominantly inherited cancer\u2010susceptibility syndrome that confers an increased risk for colorectal cancer and endometrial cancer at a young age. It also entails an increased risk of a variety of other tumors, such as ovarian, gastric, uroepithelial and biliary tract cancers. The underlying pathogenic mutation lies in 1 of the 5 known DNA MMR genes (<jats:italic>MSH2, MLH1, PMS1, PMS2<\/jats:italic> and <jats:italic>MSH6<\/jats:italic>). We screened a total of 140 individuals from 56 Spanish families with suspected HNPCC for mutations in the DNA mismatch repair genes <jats:italic>MLH1<\/jats:italic> and <jats:italic>MSH2,<\/jats:italic> using DGGE and direct DNA sequencing. Families were selected on the basis of a history of HNPCC\u2010related tumors or the occurrence of other associated tumors in members besides the index case affected with colorectal cancer. We detected 14 definite pathogenic germline mutations, 9 in <jats:italic>MLH1<\/jats:italic> and 5 in <jats:italic>MSH2<\/jats:italic> in 13 unrelated families selected by the Amsterdam criteria and Bethesda guidelines (1 family carries 2 mutations) and 3 missense mutations in 3 unrelated families selected by the Amsterdam criteria. Among the 17 germline mutations noted in the Spanish cohort, 10 are novel, 7 in <jats:italic>MLH1<\/jats:italic> and 3 in <jats:italic>MSH2,<\/jats:italic> perhaps demonstrating different mutational spectra in the Spanish population, where no founder mutation has been identified. Based on our results, we suggest that in the Spanish population not only HNPCC families fulfilling the Amsterdam criteria but also those following Bethesda guidelines should undergo genetic testing for <jats:italic>MSH2<\/jats:italic> and <jats:italic>MLH1<\/jats:italic> mutations. \u00a9 2002 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.10240","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T23:13:41Z","timestamp":1030317221000},"page":"774-779","source":"Crossref","is-referenced-by-count":34,"title":["Prevalence of germline mutations of <i>MLH1<\/i> and <i>MSH2<\/i> in hereditary nonpolyposis colorectal cancer families from Spain"],"prefix":"10.1002","volume":"98","author":[{"given":"Trinidad","family":"Caldes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Godino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"de la Hoya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iciar","family":"Garcia Carbonero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Perez 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