engleski

Involvement of APC/beta-catenin signalling and E-cadherin in sporadic colon cancer

Activation of APC/beta-catenin signalling pathway by mutation in the APC or beta-catenin gene contributes to colorectal carcinogenesis. E-cadherin is involved in control of intercellular adhesion and acts as an invasion supressor. We examined 60 cases of human sporadic colon cancer and corresponding normal tissue samples to evaluate the loss of heterozygosity (LOH) and presence of mutations at the APC and E-cadherin gene loci. The presence of beta-catenin mutations was examined in 100 sporadic colorectal tumor samples. DNAs were used for PCR, RFLP, VNTR and LOH analysis. To analyze LOH at the APC gene loci we used three RFLP intragenic markers (exon 11 RsaI, exon 15 MspI, and exon 15 AspHI). The presence of the mutations in the amplicon 15H of the APC gene, and APC gene mutation in codon 1309 were analyzed as well. To analyze mutations in the beta-catenin gene we amplified exon 3 and the intronic sequences flanking it from tumor DNAs. For the LOH analysis of E-cadherin gene locus we used D16S752 polymorphic marker. The informativity for all three APC intragenic markers was 53.3 % (32 of 60 assayed), and 25 % of tumors (8 of 32 informative) demonstrated LOH. We found two APC gene mutations in our tumor samples: a deletion in codon 1309, and an insetrion in the amplicon 15H of the APC gene. In 4 % of tumor samples (4 of 100 tested) the mutation of the beta-catenin gene was found. The informativity of D16S752 E-cadherin gene polymorphic marker was 75% (45 of 60 tested) and 28.8 % of tumors (13 of 45 informative) demonstrated LOH.

sporadic colon cancer; APC; beta-catenin; E-cadherin

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