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Genes of the WNT Signaling Pathway are Altered in Human Brain Tumors

Research carried out in this paper focused on changes of three genes, E-cadherin (CDH1), adenomatous polyposis coli (APC) and beta-catenin (CTNNB1) in a palette of 50 central nervous system tumors. All gene products are components of adherens junctions, but are also involved in the Wnt signalling pathway. PCR amplification of tetranucleotide GATA polymorphism (D16S752) linked to CDH1 gene was used to test loss of heterozygosity (LOH) of E-cadherin in brain tumor samples. Instability of the APC gene was investigated by PCR/LOH using RFLP and changes of beta-catenin were tested by heteroduplex method. The results of our analysis showed LOH of CDH1 gene in 31% of meningiomas examined. One LOH was also found in a single case of germinoma, while other tumor types did not demonstrate changes of the CDH1 gene. Fourteen samples (29.2%) with changes of the APC gene were observed out of 48 heterozygous patients. The changes were distributed to: 33.3% of glioblastomas, 27% of meningiomas, 1 LOH in five informative astocytomas (20%), and 1 in six informative neurinomas (17%). One oligoastrocytoma showed LOH at exon 11 and one medulloblastoma had allelic imbalance at both exons. There were 5 samples (10%) showing heteroduplexes encompassed in β -catenin’ s exon 3. Potential mutations were confined to two meningiomas, an astrocytoma, a glioblastoma, and a germinoma. Conclusion. The results of this research suggests that genetic changes of the wnt components are involved in brain tumor genesis. Changes of E-cadherin are involved in meningiomas, while changes of APC gene are more commonly distributed among different tumor types, with glioblastomas showing the highest percentage of changes.

tumors of the CNS; E-cadherin gene (CDH1); beta-catenin gene (CTNNB1); adenomatous polyposis coli gene (APC); genetic instabilities; wnt signaling pathway

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