PURPOSE: The molecular mechanisms and candidate genes involved in development of meningiomas still needs investigation and elucidation. METHODS: In the present study 60 meningiomas were analyzed regarding changes of tumor suppressor gene E-cadherin (CDH1), a component of adherens junction and an indirect modulator of the wnt signaling. Gene instability was tested by polymerase chain reaction/loss of heterozygosity (LOH) method. Protein expression was analyzed by immunohistochemistry. RESULTS: The results of our analysis showed altogether 32% of samples with LOH of the CDH1 gene. Interestingly, another type of genomic instability was detected; replication error-positive samples (RER+). Three out of 28 heterozygous samples were RER+ (11%). The instability is the result of impaired cellular mismatch repair. Fibrous and angiomatous cases showed higher percent of genetic changes, 67 and 75%, respectively. Immunostaining showed that overall 73% of samples had downregulation of E-cadherin expression. Intense downregulation of E-cadherin was noticed in tumors with grades II and III. Five out of nine samples with LOH were accompanied with the downregulation of E-cadherin protein expression (56%). One RER+ sample had lower expression of E-cadherin. We noticed that 36.4% of samples with lower E-cadherin expression had beta-catenin located in the nucleus. Also, 75% of samples with genomic instabilities had beta-catenin in the nucleus. Our findings demonstrated that there is significant association between the genetic changes of CDH1 and the nuclear localization of beta-catenin protein (chi(2) = 5.25, df = 1, P < 0.022). Beta-catenin was progressively upregulated from meningothelial to atypical, while 60% of anaplastic showed upregulation and nuclear localization of the protein. CONCLUSIONS: Our results suggest that genetic instabilities of the E-cadherin gene have a role in meningioma development and progression. Detected microsatellite instability indicates that mismatch repair may also be targeted in meningioma.
PURPOSE: The molecular mechanisms and candidate genes involved in development of meningiomas still needs investigation and elucidation. METHODS: In the present study 60 meningiomas were analyzed regarding changes of tumor suppressor gene E-cadherin (CDH1), a component of adherens junction and an indirect modulator of the wnt signaling. Gene instability was tested by polymerase chain reaction/loss of heterozygosity (LOH) method. Protein expression was analyzed by immunohistochemistry. RESULTS: The results of our analysis showed altogether 32% of samples with LOH of the CDH1 gene. Interestingly, another type of genomic instability was detected; replication error-positive samples (RER+). Three out of 28 heterozygous samples were RER+ (11%). The instability is the result of impaired cellular mismatch repair. Fibrous and angiomatous cases showed higher percent of genetic changes, 67 and 75%, respectively. Immunostaining showed that overall 73% of samples had downregulation of E-cadherin expression. Intense downregulation of E-cadherin was noticed in tumors with grades II and III. Five out of nine samples with LOH were accompanied with the downregulation of E-cadherin protein expression (56%). One RER+ sample had lower expression of E-cadherin. We noticed that 36.4% of samples with lower E-cadherin expression had beta-catenin located in the nucleus. Also, 75% of samples with genomic instabilities had beta-catenin in the nucleus. Our findings demonstrated that there is significant association between the genetic changes of CDH1 and the nuclear localization of beta-catenin protein (chi(2) = 5.25, df = 1, P < 0.022). Beta-catenin was progressively upregulated from meningothelial to atypical, while 60% of anaplastic showed upregulation and nuclear localization of the protein. CONCLUSIONS: Our results suggest that genetic instabilities of the E-cadherin gene have a role in meningioma development and progression. Detected microsatellite instability indicates that mismatch repair may also be targeted in meningioma.
Authors: David W Ellison; Olabisi E Onilude; Janet C Lindsey; Meryl E Lusher; Claire L Weston; Roger E Taylor; Andrew D Pearson; Steven C Clifford Journal: J Clin Oncol Date: 2005-11-01 Impact factor: 44.544
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Authors: Dieter-Chichung Lie; Sophia A Colamarino; Hong-Jun Song; Laurent Désiré; Helena Mira; Antonella Consiglio; Edward S Lein; Sebastian Jessberger; Heather Lansford; Alejandro R Dearie; Fred H Gage Journal: Nature Date: 2005-10-27 Impact factor: 49.962
Authors: Patrícia Domingues; María González-Tablas; Álvaro Otero; Daniel Pascual; Laura Ruiz; David Miranda; Pablo Sousa; Jesús María Gonçalves; María Celeste Lopes; Alberto Orfao; María Dolores Tabernero Journal: Oncotarget Date: 2015-05-10