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MGMT-Methylated Alleles Are Distributed Heterogeneously Within Glioma Samples Irrespective of IDH Status and Chromosome 10q Deletion

Several molecular markers drive diagnostic classification, prognostic stratification, and/or prediction of response to therapy in patients with gliomas. Among them, IDH gene mutations are valuable markers for defining subtypes and are strongly associated with epigenetic silencing of the methylguanin...

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Autores principales: Fontana, Laura, Tabano, Silvia, Bonaparte, Eleonora, Marfia, Giovanni, Pesenti, Chiara, Falcone, Rossella, Augello, Claudia, Carlessi, Nicole, Silipigni, Rosamaria, Guerneri, Silvana, Campanella, Rolando, Caroli, Manuela, Maria Sirchia, Silvia, Bosari, Silvano, Miozzo, Monica
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5409217/
https://www.ncbi.nlm.nih.gov/pubmed/27346749
http://dx.doi.org/10.1093/jnen/nlw052
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author Fontana, Laura
Tabano, Silvia
Bonaparte, Eleonora
Marfia, Giovanni
Pesenti, Chiara
Falcone, Rossella
Augello, Claudia
Carlessi, Nicole
Silipigni, Rosamaria
Guerneri, Silvana
Campanella, Rolando
Caroli, Manuela
Maria Sirchia, Silvia
Bosari, Silvano
Miozzo, Monica
author_facet Fontana, Laura
Tabano, Silvia
Bonaparte, Eleonora
Marfia, Giovanni
Pesenti, Chiara
Falcone, Rossella
Augello, Claudia
Carlessi, Nicole
Silipigni, Rosamaria
Guerneri, Silvana
Campanella, Rolando
Caroli, Manuela
Maria Sirchia, Silvia
Bosari, Silvano
Miozzo, Monica
author_sort Fontana, Laura
collection PubMed
description Several molecular markers drive diagnostic classification, prognostic stratification, and/or prediction of response to therapy in patients with gliomas. Among them, IDH gene mutations are valuable markers for defining subtypes and are strongly associated with epigenetic silencing of the methylguanine DNA methyltransferase (MGMT) gene. However, little is known about the percentage of MGMT-methylated alleles in IDH-mutated cells or the potential association between MGMT methylation and deletion of chromosome 10q, which encompasses the MGMT locus. Here, we quantitatively assessed MGMT methylation and IDH1 mutation in 208 primary glioma samples to explore possible differences associated with the IDH genotype. We also explored a potential association between MGMT methylation and loss of chromosome 10q. We observed that MGMT methylation was heterogeneously distributed within glioma samples irrespective of IDH status suggesting an incomplete overlap between IDH1-mutated and MGMT-methylated alleles and indicating a partial association between these 2 events. Moreover, loss of one MGMT allele did not affect the methylation level of the remaining allele. MGMT was methylated in about half of gliomas harboring a 10q deletion; in those cases, loss of heterozygosity might be considered a second hit leading to complete inactivation of MGMT and further contributing to tumor progression.
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spelling pubmed-54092172017-05-03 MGMT-Methylated Alleles Are Distributed Heterogeneously Within Glioma Samples Irrespective of IDH Status and Chromosome 10q Deletion Fontana, Laura Tabano, Silvia Bonaparte, Eleonora Marfia, Giovanni Pesenti, Chiara Falcone, Rossella Augello, Claudia Carlessi, Nicole Silipigni, Rosamaria Guerneri, Silvana Campanella, Rolando Caroli, Manuela Maria Sirchia, Silvia Bosari, Silvano Miozzo, Monica J Neuropathol Exp Neurol Original Articles Several molecular markers drive diagnostic classification, prognostic stratification, and/or prediction of response to therapy in patients with gliomas. Among them, IDH gene mutations are valuable markers for defining subtypes and are strongly associated with epigenetic silencing of the methylguanine DNA methyltransferase (MGMT) gene. However, little is known about the percentage of MGMT-methylated alleles in IDH-mutated cells or the potential association between MGMT methylation and deletion of chromosome 10q, which encompasses the MGMT locus. Here, we quantitatively assessed MGMT methylation and IDH1 mutation in 208 primary glioma samples to explore possible differences associated with the IDH genotype. We also explored a potential association between MGMT methylation and loss of chromosome 10q. We observed that MGMT methylation was heterogeneously distributed within glioma samples irrespective of IDH status suggesting an incomplete overlap between IDH1-mutated and MGMT-methylated alleles and indicating a partial association between these 2 events. Moreover, loss of one MGMT allele did not affect the methylation level of the remaining allele. MGMT was methylated in about half of gliomas harboring a 10q deletion; in those cases, loss of heterozygosity might be considered a second hit leading to complete inactivation of MGMT and further contributing to tumor progression. Oxford University Press 2016-08 2016-06-24 /pmc/articles/PMC5409217/ /pubmed/27346749 http://dx.doi.org/10.1093/jnen/nlw052 Text en © 2016 American Association of Neuropathologists, Inc. http://creativecommons.org/licenses/by-nc/4.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Original Articles
Fontana, Laura
Tabano, Silvia
Bonaparte, Eleonora
Marfia, Giovanni
Pesenti, Chiara
Falcone, Rossella
Augello, Claudia
Carlessi, Nicole
Silipigni, Rosamaria
Guerneri, Silvana
Campanella, Rolando
Caroli, Manuela
Maria Sirchia, Silvia
Bosari, Silvano
Miozzo, Monica
MGMT-Methylated Alleles Are Distributed Heterogeneously Within Glioma Samples Irrespective of IDH Status and Chromosome 10q Deletion
title MGMT-Methylated Alleles Are Distributed Heterogeneously Within Glioma Samples Irrespective of IDH Status and Chromosome 10q Deletion
title_full MGMT-Methylated Alleles Are Distributed Heterogeneously Within Glioma Samples Irrespective of IDH Status and Chromosome 10q Deletion
title_fullStr MGMT-Methylated Alleles Are Distributed Heterogeneously Within Glioma Samples Irrespective of IDH Status and Chromosome 10q Deletion
title_full_unstemmed MGMT-Methylated Alleles Are Distributed Heterogeneously Within Glioma Samples Irrespective of IDH Status and Chromosome 10q Deletion
title_short MGMT-Methylated Alleles Are Distributed Heterogeneously Within Glioma Samples Irrespective of IDH Status and Chromosome 10q Deletion
title_sort mgmt-methylated alleles are distributed heterogeneously within glioma samples irrespective of idh status and chromosome 10q deletion
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5409217/
https://www.ncbi.nlm.nih.gov/pubmed/27346749
http://dx.doi.org/10.1093/jnen/nlw052
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