title: Somatic mutations of APC gene in carcinomas from hereditary non-polyposis colorectal cancer patients.
abstract: OBJECTIVE
  To investigate the mutational features of adenomatous polyposis coli (APC) gene and its possible arising mechanism in hereditary non-polyposis colorectal cancers (HNPCC).
  
  
  METHODS
  PCR-based In Vitro Synthesized Protein Test (IVSP) assay and sequencing analysis were used to confirm somatic mutations of whole APC gene in 19 HNPCC cases.
  
  
  RESULTS
  Eleven cases with 13 mutations were determined to harbor APC mutations. The prevalence of APC mutation was 58%(11/19). The mutations consisted of 9 frameshift and 4 nonsense ones, indicating that there were more frameshift mutations (69%). The frameshift mutations all exhibited 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 mutations presented C-to-T transitions at CpG sites.
  
  
  CONCLUSIONS
  Mutations of APC gene were detected in more than half of HNPCC, indicating that its mutation was a common molecular event and might play an important role in the tumorigenesis of HNPCC. Locations of frameshift mutations at simple nucleotide repeat sequences and point mutations at CpG sites suggested that many mutations probably derived from endogenous processes including mismatch repair (MMR) deficiency. Defective MMR might affect the nature of APC mutations in HNPCC and likely occur earlier than APC mutational inactivation in some patients.
authors.affiliation: Department of Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China. hjys@zju.edu.cn
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
authors.forename: Shu
authors.initials: S
authors.lastname: Zheng
authors.forename: Shen-Hang
authors.initials: SH
authors.lastname: Jin
authors.forename: Su-Zhan
authors.initials: SZ
authors.lastname: Zhang
mesh_terms: D002277:Carcinoma / Q000235:genetics*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D005787:Gene Frequency; D017491:Genes, APC; D006801:Humans; D009154:Mutation; D020133:Reverse Transcriptase Polymerase Chain Reaction