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Genetic changes of CDH1, APC and CTNNB1 found in human brain tumors

This study focused on changes of E-cadherin (CDH1), adenomatous polyposis coli (APC) and beta-catenin (CTNNB1) in a palette of 50 CNS tumors. All gene products are components of adherens junctions, but are also involved in the Wnt signalling. PCR amplification of D16S752 polymorphism linked to CDH1 gene was used to test loss of heterozygosity (LOH) in tumors. Instability of APC gene was investigated by PCR/LOH using RFLP, and changes of CTNNB1 were tested by heteroduplex. The results showed LOH of CDH1 gene in 31% of meningiomas examined (correlation significant at 0.002 level). One LOH was also found in germinoma, while other tumor types did not show changes of CDH1. Fourteen samples (29.2%) with changes of APC were observed. 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 two exons. Ten % of our sample (two meningiomas, an astrocytoma, a glioblastoma, and a germinoma) showed heteroduplexes encompassed in β -catenin’ s exon 3. Our results suggest that genetic changes of the wnt components are involved in brain tumor genesis. Changes of CDH1 are involved in meningiomas, while changes of APC are distributed among different tumor types, with glioblastomas showing the highest percentage.

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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