[Characteristics of APC gene mutations in colorectal tumors]

To investigate the mutational features of adenomatous polyposis coli (APC) gene and their possible arising mechanism in colorectal tumors.

PCR-based IVSP assay (in vitro synthesized protein test) and sequence analysis were used to determine somatic mutations of whole APC gene in 115 cases with non familial adenomatous polyposis(non-FAP) colorectal tumors.

Seventy-six mutated cases with 101 mutations were confirmed in the study. Analysis of the spectra of APC mutations revealed that frameshift mutations were more common than point ones(56% vs 44%), ninety-one percent of them being insertions/deletions of 1-2 bp, particularly single A (61%) and 51% of point mutations locating at CpG sites. In comparison with sporadic tumors, hereditary nonpolyposis colorectal cancer (HNPCC) was found to have more frameshift mutations (69% vs 52%, P<0.05), less point mutations at CpG site (31% vs 50%, P<0.05), and a slightly lower frequency of mutations(53% vs 67%, P>0.05). There was no difference in mutational distribution of segment 3 between them (38% vs 46%, P>0.05). It was also found that 15 cases(20%) had double mutations with distance ranging from 7 to 1443 bp, suggesting the coexistance of allelic and non-allelic mutations.

Based on the mutational spectra of APC gene in colorectal tumors, it can be concluded that most of gene mutations are probably related to DNA mismatch repair deficiency, and the APC mutational patterns of HNPCC and sporadic tumors are quite different. The reason of coexistance of allelic and non-allelic mutations needs to be investigated.