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

This paper focuses on changes in E-cadherin (CDH1), adenomatous polyposis coli (APC), and beta-catenin (CTNNB1) in 50 tumors of the central nervous system. All gene products are components of adherens junctions, but are also involved in wnt signaling. The results of our analysis showed LOH of CDH1 gene in 31% of meningiomas examined (significant correlation; p=0.002). LOH was noted in a single case of germinoma, while other tumor types did not demonstrate any change in CDH1. Fourteen samples (29.2%) with changes in APC gene were observed. The changes were seen in 33.3% of glioblastomas and in 27% of meningiomas; LOH occurred in five informative astocytomas (20%) and in six informative neurinomas (17%). One oligoastrocytoma showed LOH at exon 11, and one medulloblastoma had allelic imbalance at both exons. Five samples (10%) showed heteroduplexes in exon 3 of beta-catenin. Potential mutations were confined to two meningiomas, one astrocytoma, one glioblastoma, and one germinoma. Our results suggest that genetic changes in wnt components are involved in brain tumor genesis. Changes in E-cadherin are involved in meningiomas, while changes in APC gene occur in different tumor types, with glioblastomas showing the highest percentage

A Case of Prenatal Neurocytoma Associated With ATR-16 Syndrome

A Case of Prenatal Neurocytoma Associated With ATR-16 Syndrom

Meningiomas exhibit loss of heterozygosity of the APC gene

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