Detection of APC germ line mosaicism in patients with de novo familial adenomatous polyposis: a plea for the protein truncation test.

Background: Familial adenomatous polyposis (FAP) is an autosomal dominantly inherited colorectal cancer predisposition caused by germ line mutations in the APC (adenomatous polyposis coli) gene. Current recommendations for APC mutation analysis advise full gene sequencing to identify point mutations and small insertions/deletions as well as the multiplex ligation dependent probe amplification (MLPA) technique to detect gene dosage alterations. Use of the protein truncation test (PTT) as a pre-screening tool has thus been largely replaced with direct end-to-end sequencing, mainly because of its limited sensitivity and failure to identify APC missense alterations.