Analysis of somatic APC mutations in rare extracolonic tumors of patients with familial adenomatous polyposis coli
Article first published online: 12 JUL 2004
Copyright © 2004 Wiley-Liss, Inc.
Genes, Chromosomes and Cancer
Volume 41, Issue 2, pages 93–98, October 2004
How to Cite
Bläker, H., Sutter, C., Kadmon, M., Otto, H. F., von Knebel-Doeberitz, M., Gebert, J. and Helmke, B. M. (2004), Analysis of somatic APC mutations in rare extracolonic tumors of patients with familial adenomatous polyposis coli. Genes Chromosom. Cancer, 41: 93–98. doi: 10.1002/gcc.20071
- Issue published online: 26 JUL 2004
- Article first published online: 12 JUL 2004
- Manuscript Accepted: 25 MAY 2004
- Manuscript Received: 1 MAR 2004
Patients with familial adenomatous polyposis coli (FAP) carry heterozygous mutations of the APC gene. At a young age, these patients develop multiple colorectal adenomas that consistently display a second somatic mutation in the remaining APC wild-type allele. Inactivation of APC leads to impaired degradation of β-catenin, thereby promoting continuous cell-cycle 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 APC germ-line 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-hit somatic mutations in the mutational cluster region of the APC gene. Immunohistochemistry was performed to compare the expression pattern of β-catenin to the mutational status of the APC gene. Exon 3 of the β-catenin gene (CTNNB1) was analyzed for activating mutations to investigate alternative mechanisms of elevated β-catenin concentration. Although CTNNB1 mutations were not observed, second somatic APC 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 β-catenin. No APC mutations were seen in focal nodular hyperplasia of the liver, angiofibrolipoma, and seborrheic wart. This is the first study reporting second somatic APC mutations in FAP-associated 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. © 2004 Wiley-Liss, Inc.