title: Meningiomas exhibit loss of heterozygosity of the APC gene.
abstract: The molecular mechanisms and candidate genes involved in development of meningiomas still need investigation and elucidation. In the present study 33 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 four LOHs were exclusive for exon 11 and four 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 (chi(2 )= 13.81, df = 2, P < 0.001). We also showed that nuclear localization of beta-catenin correlates to APC genetic changes (chi(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.
authors: Laboratory of Neurooncology, Croatian Institute for Brain Research, Medical School University of Zagreb, Salata 12, 10000, Zagreb, Croatia. nina@mef.hr
authors: Nives
authors: N
authors: Pećina-Slaus
authors: Tamara
authors: T
authors: Nikuseva Martić
authors: Davor
authors: D
authors: Tomas
authors: Vili
authors: V
authors: Beros
authors: Martina
authors: M
authors: Zeljko
authors: Hrvoje
authors: H
authors: Cupić
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D017491:Genes, APC; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D008297:Male; D008577:Meningeal Neoplasms / Q000235:genetics* / Q000473:pathology; D008579:Meningioma / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length