{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T11:55:01Z","timestamp":1791114901191,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2004,7,12]],"date-time":"2004-07-12T00:00:00Z","timestamp":1089590400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Chromosomes &amp;amp; Cancer"],"published-print":{"date-parts":[[2004,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Patients with familial adenomatous polyposis coli (FAP) carry heterozygous mutations of the <jats:italic>APC<\/jats:italic> gene. At a young age, these patients develop multiple colorectal adenomas that consistently display a second somatic mutation in the remaining <jats:italic>APC<\/jats:italic> wild\u2010type allele. Inactivation of APC leads to impaired degradation of \u03b2\u2010catenin, thereby promoting continuous cell\u2010cycle progression. The role of APC inactivation in rare extracolonic tumors of FAP patients has not been characterized sufficiently. Among tissue specimen from 174 patients with known <jats:italic>APC<\/jats:italic> germ\u2010line mutations, we identified 8 tumors infrequently seen in FAP. To investigate the pathogenic role of APC pathway deregulation in these lesions, they were analyzed for second\u2010hit somatic mutations in the mutational cluster region of the <jats:italic>APC<\/jats:italic> gene. Immunohistochemistry was performed to compare the expression pattern of \u03b2\u2010catenin to the mutational status of the <jats:italic>APC<\/jats:italic> gene. Exon 3 of the \u03b2\u2010catenin gene (<jats:italic>CTNNB1<\/jats:italic>) was analyzed for activating mutations to investigate alternative mechanisms of elevated \u03b2\u2010catenin concentration. Although <jats:italic>CTNNB1<\/jats:italic> mutations were not observed, second somatic <jats:italic>APC<\/jats:italic> mutations were found in 4 of the 8 tumors: a uterine adenocarcinoma, a hepatocellular adenoma, an adrenocortical adenoma, and an epidermal cyst. These tumors showed an elevated concentration of \u03b2\u2010catenin. No <jats:italic>APC<\/jats:italic> mutations were seen in focal nodular hyperplasia of the liver, angiofibrolipoma, and seborrheic wart. This is the first study reporting second somatic <jats:italic>APC<\/jats:italic> mutations in FAP\u2010associated uterine adenocarcinoma and epidermal cysts. Furthermore, our data strengthen a role for impaired APC function in the pathogenesis of adrenal and hepatic neoplasms in FAP patients. \u00a9 2004 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/gcc.20071","type":"journal-article","created":{"date-parts":[[2004,7,12]],"date-time":"2004-07-12T18:02:51Z","timestamp":1089655371000},"page":"93-98","source":"Crossref","is-referenced-by-count":50,"title":["Analysis of somatic <i>APC<\/i> mutations in rare extracolonic tumors of patients with familial adenomatous polyposis coli"],"prefix":"10.1002","volume":"41","author":[{"given":"Hendrik","family":"Bl\u00e4ker","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Sutter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Kadmon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herwart 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