GERMLINE AND SOMATIC MUTATIONS OF APC GENE AND THE GENOTYPE-PHENOTYPE ANALYSIS IN FAP AND SPORADIC COLORECTAL CANCERS

摘要

Genomic DNA was extracted from peripheral blood lymphocytes of 22 FAP and from normal/tumor colorectal tissues of 43 sporadic colorectal cancers. APC gene was screened for germline and somatic mutations with systematic analysis techniques including DHPLC, PTT, MLPA and DNA sequencing. Germline APC mutations were identified in 13 of 22 FAP patients, and somatic mutations were found in 18 of 43 tumors of patients with sporadic colorectal cancers. One germline and nine somatic mutations found in this study was novel. The clinical features of FAP were related to the positions of germline mutations carried in APC gene. The ratio of tumors uncovered somatic APC mutations in the younger CRC patients was higher than that in the older patients. The sporadic colorectal cancer with a mutation between the codon 1020 and 1169 of APC gene had a higher frequency of tumor metastasis. Our results in this study indicate that the phenotype of some FAP and sporadic colorectal cancers may be predisposed by the genotype of APC gene that is involved in a genetic pathway in tumorigenesis.