engleski

WNT Signal Transduction Pathway is Targeted in Meningioma

The molecular mechanisms and candidate genes involved in development of meningiomas still need investigation and elucidation. In the present study thirty-three meningiomas were analyzed regarding genetic changes of tumor suppressor gene Adenomatous polyposis coli (APC), a component of the wnt signaling. Gene instability was tested by polymerase chain reaction/loss of heterozygosity (LOH) using Restriction Fragment Length Polymorphism (RFLP) method. RFLP was performed by two genetic markers, Rsa I in APC’ s exon 11 and Msp I in its exon 15. The results of our analysis showed altogether 15 samples with LOH of the APC gene out of 32 heterozygous patients (47%). Seven patients had LOHs at both exons, while 4 LOHs were exclusive for exon 11 and 4 for exon 15. The changes were distributed according to pathohistological grade as follows: 46% of meningothelial meningioma showed LOH ; 33% of fibrous ; 75% of mixed (transitional) ; 75% of angiomatous, and one LOH was found in a single case of psammomatous meningioma. None of the LOHs were found in atypical and anaplastic cases. Immunostaining showed that samples with LOHs were accompanied with the absence of APC protein expression or presence of mutant APC proteins ( 2 =13.81, df = 2, P 0.001). We also showed that nuclear localization of beta-catenin correlates to APC genetic changes ( 2 =21, 96, df = 2, P 0.0001). The results of this investigation suggest that genetic changes of APC gene play a role in meningioma formation.

Wnt; APC; meningioma

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