Naslov
APC, beta-catenin and E-cadherin genetic changes in colorectal carcinogenesis

Autori
Čačev, Tamara ; Spaventi, Radan ; Pavelić, Krešimir ; Kapitanović, Sanja

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Revista de Oncologia 4 Suppl 1 / EACR - Granada : Federacion de Sociedades Espanolas de Oncologia y del Instituto Nacional de Cancerologia de Mexico, 2002

Skup
17th Meeting of the European Association for Cancer Research

Mjesto i datum
Granada, Španjolska, 08.06.2002. - 11.06.2002

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
APC; beta-catenin; E-cadherin; colon cancer

Sažetak
Background: Activation of APC/beta-catenin signalling pathway by mutation in either the APC or beta-catenin gene contributes to colorectal carcinogenesis. E-cadherin is involved in control and maintenance of normal intercellular adhesion and acts as a strong 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, beta-catenin and E-cadherin gene loci. Methods: 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 15H amplicon of the APC gene, and most frequent APC gene mutation in codon 1309 were analyzed as well. To analyze mutations in the beta-catenin gene we amplified exon 3 and the entire intronic sequences flanking it from genomic DNAs of all 60 tumors. For the LOH analysis of E-cadherin gene locus we used D16S752 polymorphic marker. Results: 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 5bp deletion in codon 1309, and an insertion in the 15H amplicon of the APC gene. In 3.3 % of tumor samples (2 of 60 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. Conclusion: Our study showed that activation of the APC/beta-catenin signalling and loss of E-cadherin function are important events in colorectal cancerogenesis.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA