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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...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2016
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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. |
format | Online Article Text |
id | pubmed-5409217 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
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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