Genetic Variations of the CTNNA1 And The CTNNB1 Genes in Sporadic Colorectal Cancer in Polish Population

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Abstract

Experimental as well as clinical observations have demonstrated that the E-cadherin/catenin complex is a powerful inhibitor of invasion. Abrogation of this pathway is implicated in the carcinogenesis of several malignancies, especially colorectal cancer.

The aim of the study was to determine the CTNNA1 and the CTNNB1 mutations and its relationship to clinical and pathological features of sporadic colorectal cancer (CRC) in Polish patients.

Material and methods. Paired tumor and normal tissue samples from 110 sporadic CRC patients undergoing resective surgery were prospectively studied for the alpha catenin (CTNNA1) gene and beta catenin (CTNNB1)gene mutations by PCR/single strand conformation polymorphism (SSCP).

Results. The CTNNA1 gene alteration in exon 7 were detected in 4 samples and in exon 3 of CTNNB1 gene were found in 3 samples. There was a trend at the limit of statistical significance associating younger age at diagnosis (<50) with CTNNA1 and the CTNNB1 mutations. The mutation of CTNNB1 seemed to occur more frequently in the proximal colon than distal. The CRC patients with CTNNA1 mutation had a significantly increased lymph node metastasis. On the other hand, there was no correlation between mutations and the other clinical variables (e.g. sex, grade and depth of invasion).

Conclusion. Although we found a low frequency of mutations in the CTNNA1 and the CTNNB1 genes, but the analysis the relationship with clinical and pathological features of CRC patients may indicated an association of these mutations with the risk and progression of CRC.

1. W ijnhoven BP, Dinjens WN , Pignatelli M: E-cadherin- catenin cell-cell adhesion complex and human cancer. Br J Surg 2000; 87: 992-1005.

2. S cholten AN , Aliredjo R, Creutzberg CL, SmitVT: Combined E-cadherin, _-catenin, and _-catenin expression is a favorable prognostic factor in endometrial carcinoma. Int J Gynecol Cancer 2006; 16: 1379-85.

3. K obielak A, Fuchs E: Alpha-catenin: at the junction of intercellular adhesion and actin dynamics.

Nat Rev Mol Cell Biol 2004; 5(8): 614-25.

4. Gumbiner BM: Cell adhesion: the molecular basis of tissue architecture and morphogenesis. Cell 1996; 84: 345-57.

5. Lustig B, Behrens J: The Wnt signaling pathway and its role in tumor development. J Cancer ResClin Oncol 2003; 129: 199-221.

6. Shimoyama Y et al.: Cadherin dysfunction in a human cancer cell line: possible involvement of loss of α-catenin expression in reduced cell-cell adhesiveness. Cancer Res 1992; 52: 5770-74.

7. Morton RA, Ewing CM, Nagafuchi A et al.: Reduction of E-cadherin levels and deletion of the α-catenin gene in human prostate cancer cells.

Cancer Res 1993; 53: 3585-90.

8. Vermeulen SJ, Nollet F, Teugels E et al.: The alphaE-catenin gene (CTNNA1) acts as an invasion- suppressor gene in human colon cancer cells.

Oncogene 1999; 28; 18(4): 905-15.

9. Shibata H, Takano H, Ito M et al.: Alpha-catenin is essential in intestinal adenoma formation.

Proc Natl Acad Sci USA . 2007; 104 (46): 18199-204.

10. Giannini AL , Vivanco M, Kypta RM : alphacatenin inhibits beta-catenin signaling by preventing formation of a beta-catenin*T-cell factor*DNA complex. J Biol Chem 2000; 21; 275(29): 21883-88.

11. Baldus SE, Monig SP, Huxel S et al.: MUC1 and nuclear beta-catenin are coexpressed at the invasion front of colorectal carcinomas and are both correlated with tumor prognosis. Clin Cancer Res 2004; 10: 2790-96.

12. R aftopoulos I, Davaris P, Karatzas G et al.: Level of alpha-catenin expression in colorectal cancer correlates with invasiveness, metastatic potential, and survival. J Surg Oncol 1998; 68(2): 92-99.

13. K im IJ, Kang HC, Park JH et al.: Development and applications of a beta-catenin oligonucleotide microarray: beta-catenin mutations are dominantly found in the proximal colon cancers with microsatellite instability. Clin Cancer Res 2003; 1; 9(8): 2920-25.14. Albuquerque C, Baltazar C, Filipe B et al.: Colorectal cancers show distinct mutation spectra in members of the canonical WNT signaling pathway according to their anatomical location and type of genetic instability. Genes Chromosomes Cancer 2010; 49(8): 746-59.

15. Vanpoucke G, Nollet F, Tejpar S et al.: The human alphaE-catenin gene CTNNA1: mutational analysis and rare occurrence of a truncated splice variant. Biochim Biophys Acta 2002; 12; 1574(3): 262-68.

16. Ebert MP, Fei G, Kahmann S et al.: Increased beta-catenin mRNA levels and mutational alterations of the APC and beta-catenin gene are present in intestinal-type gastric cancer. Carcinogenesis 2002; 23(1): 87-91.

17. I wao K , Nakamori S, Kameyama M et al. Activation of the β-catenin gene by interstitial deletions involving exon 3 in primary colorectal carcinomas without adenomatous polyposis coli mutations.

Cancer Res 1998; 58: 1021-26.

18. Khiari M, Arfaoui A, Kriaa L et al.: The prognostic value of the immunohistochemical expression and mutational pattern of the key mediator of Wnt signaling: beta-catenin in Tunisian patients with colorectal carcinoma. Appl ImmunohistochemMol Morphol 2012; 20(1): 62-70.

19. K itaeva MN , Grogan L, Williams JP et al.: Mutations in beta-catenin are uncommon in colorectal cancer occurring in occasional replication error-positive tumors. Cancer Res 1997; 57: 4478-81.

20. Langner E, Przybylowska K, Trzcinski R et al.: Loss of hMSH2 gene expression correlates with improved survival in patients with sporadic colorectal cancer. J Genet 2010; 89(1): 101-04.

21. Glebov OK , Rodriguez LM , Nakahara K et al.: Distinguishing right from left colon by the pattern of gene expression. Cancer Epidemiol Biomark Prev 2003; 12: 755-62.

22. Sugai T, Habano W, Jiao YF et al.: Analysis of molecular alterations in left- and right-sided colorectal carcinomas reveals distinct pathways of carcinogenesis: Proposal for new molecular profile of colorectal carcinomas. J Mol Diagn 2006; 8: 193-201.

23. S hiozaki H, Iihara K, Oka H et al.: Immunohistochemical detection of alpha-catenin expression in human cancers. Am J Pathol 1994; 144: 667-74

24. Gofuku J, Shiozaki H, Tsujinaka T et al.: Expression of E-cadherin and alpha-catenin in patients with colorectal carcinoma. Correlation with cancer invasion and metastasis. Am J ClinPathol 1999; 111: 29-37.

Polish Journal of Surgery

The Journal of Foundation of the Polish Journal of Surgery

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