Germline mutations are frequent in the APC gene but absent in the beta-catenin gene in familial adenomatous polyposis patients

Inactivation of the adenomatous polyposis coli (APC) gene has been shown to initiate the majority of colorectal cancer (CRC), including a familial for m called familial adenomatous polyposis (FAP). One consequence of the APC m utation is the activation of the beta-catenin (CTNNB1)/T-cell transcription factor (Tcf) pathway. A recent study has shown that about half of the spor adic CRC lacking APC mutation has CTNNB1 mutation, suggesting that CTNNB1 m utation can substitute for APC mutation in the initiation of colorectal tum origenesis. However, the frequency of CTNNB1 germline mutation in FAP has n ot been reported. In the present study, we investigated the frequencies of APC and CTNNB1 germline mutations in 26 unrelated FAP families. We used the Protein Truncation Test (PTT) to screen the entire coding region of APC an d found germline mutations in twenty families. We then screened for CTNNB1 germline mutations in the rest of the families lacl<ing detectable APC muta tions. No missense mutations at GSK-3 beta phosphorylation sites or interst itial deletion of exon 3 of CTNNB1 was found. Our results indicate that APC germline mutations are frequent but CTNNB1 germline mutations are rare in FAP patients, suggesting that CTNNB1 mutation cannot substitute for APC mut ation in the initiation of FAP. Genes Chromosomes Cancer 25:396-398, 1999. (C) 1999 Wiley-Liss, Inc.