[Mutational studies of adenomatous polyposis coli gene in carcinomas from patients with hereditary non-polyposis colorectal cancers].
OBJECTIVE
To analyze the mutational features of adenomatous polyposis coli (APC) gene and to explore the effect of mismatch repair (MMR) deficiency on its mutations 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 patients.


RESULTS
Eleven cases with thirteen mutations were determined. The frequency of APC mutation was 58%(11/19). The exhibiting mutations consisted of 9 frameshift mutations and 4 nonsense ones, indicating the existence of more frameshift mutations (69%). All of frameshift mutations were 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 of four nonsense mutations resulted from C to T transitions at CpG sites.


CONCLUSIONS
Mutational inactivations of APC gene were detected in more than half of HNPCC patients in this study, indicating that APC mutation is a common molecular event in the tumorigenesis of HNPCC. According to the location of frameshift mutations at simple nucleotide repeat sequences and point mutations at CpG sites, it was suggested that endogenous mechanisms like MMR deficiency might exert an effect on the nature of APC mutations in most HNPCC.
Huang
Jian
J
Department of Oncology, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310009 PR China. hjys@zju.edu.cn
Jin
Shen-hang
SH
Zhang
Shu-zhan
SZ
Zheng
Shu
S
D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics* / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics; D017491:Genes, APC / Q000502:physiology*; D006801:Humans
D025601:Adenomatous Polyposis Coli Protein