Somatic mutations of APC gene in carcinomas from hereditary non-polyposis colorectal cancer patients

AIM:To investigate the mutational features of adenomatouspolyposis coli (APC) gene and its possible arising mechanismin hereditary non-polyposis colorectal cancers (HNPCC).METHODS:PCR-based In Vitro Synthesized Protein Test(IVSP) assay and sequencing analysis were used to confirmsomatic mutations of whole APC gene in 19 HNPCC cases.RESULTS:Eleven cases with 13 mutations were determinedto harbor APC mutations.The prevalence of APC mutationwas 58%(11/19).The mutations consisted of 9 frameshiftand 4 nonsense ones,indicating that there were moreframeshift mutations (69%).The frameshift mutations allexhibited deletion or insertion of 1-2 bp and most of them(7/9) happened at simple nucleotide repeat sequences,particularly within (A)n tracts (5/9).All point mutationspresented C-to-T transitions at CpG sites.CONCLUSION:Mutations of APC gene were detected inmore than half of HNPCC,indicating that its mutation was acommon molecular event and might play an important rolein the tumorigenesis of HNPCC.Locations of frameshiftmutations at simple nucleotide repeat sequences and pointmutations at CpG sites suggested that many mutationsprobably derived from endogenous processes includingmismatch repair (MMR) deficiency.Defective MMR mightaffect the nature of APC mutations in HNPCC and likely occurearlier than APC mutational inactivation in some patients.