Germline mutations of the APC gene in Korean familial adenomatous polyposis patients

We extensively analyzed genomic DNA and messenger RNA (mRNA) from 62 unrelated Korean patients with familial adenomatous polyposis (FAP) for identification of germline adenomatous polyposis coli (APC) gene mutations. We adopted both single-strand conformation polymorphism (SSCP) analysis and a method of analysis involving the reverse transcription-polymerase chain reaction (RT-PCR) followed by a protein truncation test (PTT). DNA sequencing confirmed all alterations represented by aberrant bands. Germline mutations were identified in 38 patients (61%). Nineteen of the detected mutations were presumed to be novel, thus emphasizing the heterogeneity of the mutational spectrum in Korean FAP patients. In the initial 48 patients, SSCP analysis was followed by PTT for those patients for whom no detectable mutations were found by SSCP. Using this combined approach, we identified germline APC gene mutations in 29 of the 48 FAP patients (60%), including 6 patients in whom SSCP analysis failed to distinguish the mutant allele. In the 14 later patients, we identified truncating mutations in 9 patients (64%) using PTT only. Our results confirm that the mutation detection rate with PTT was superior to that with SSCP, and suggest that PTT would be a more practical screening method to detect germline mutations of the APC gene in FAP patients.