Somatic mutations of APC gene in carcinomas from hereditary non-polyposis colorectal cancer patients.
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.
Huang
Jian
J
Department of Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China. hjys@zju.edu.cn
Zheng
Shu
S
Jin
Shen-Hang
SH
Zhang
Su-Zhan
SZ
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