Klin Onkol 2006; 19(Suppl): 63-67.
Summary
Familial adenomatous polyposis is an autosomal dominant predisposition to colorectal cancer and is caused by germline mutations in the APC gene. A milder phenotype is found in patients affected with attenuated familial adenomatous polyposis or multiple adenomas. Patients with multiple adenomas might be associated with germline mutations in the MYH gene. We studied a cohort of 230 adenomatous polyposis families; we screened the entire APC coding region using the combination of denaturing gradient gel electrophoresis and/or a protein truncation test and direct sequencing. We detected 66 different mutations in 93 families; 42 of the mutations were unique. The APC mutation negative patients have been screened for large APC deletions using multiplex ligation dependent probe amplification and for germline mutations in the MYH gene using the denaturing high performance liquid chromatography (system WAVE; Transgenomic) and direct sequencing. Two families showed aconstitutional deletion of the entire APC gene and one family a single exon deletion. The most common biallelic germline mutation in the MYH gene was detected in two families. Correlations between the localization of germline mutations and clinical manifestations of the diseases are discussed.
