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The level of activity of the alternative lengthening of telomeres correlates with patient age in IDH-mutant ATRX-loss-of-expression anaplastic astrocytomas

All cancer cells need to maintain functional telomeres to sustain continuous cell division and proliferation. In human diffuse gliomas, functional telomeres are maintained due either to reactivation of telomerase expression, the main pathway in most cancer types, or to activation of a mechanism call...

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Autores principales: Grandin, Nathalie, Pereira, Bruno, Cohen, Camille, Billard, Pauline, Dehais, Caroline, Carpentier, Catherine, Idbaih, Ahmed, Bielle, Franck, Ducray, François, Figarella-Branger, Dominique, Delattre, Jean-Yves, Sanson, Marc, Lomonte, Patrick, Poncet, Delphine, Verrelle, Pierre, Charbonneau, Michel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6842523/
https://www.ncbi.nlm.nih.gov/pubmed/31706351
http://dx.doi.org/10.1186/s40478-019-0833-0
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author Grandin, Nathalie
Pereira, Bruno
Cohen, Camille
Billard, Pauline
Dehais, Caroline
Carpentier, Catherine
Idbaih, Ahmed
Bielle, Franck
Ducray, François
Figarella-Branger, Dominique
Delattre, Jean-Yves
Sanson, Marc
Lomonte, Patrick
Poncet, Delphine
Verrelle, Pierre
Charbonneau, Michel
author_facet Grandin, Nathalie
Pereira, Bruno
Cohen, Camille
Billard, Pauline
Dehais, Caroline
Carpentier, Catherine
Idbaih, Ahmed
Bielle, Franck
Ducray, François
Figarella-Branger, Dominique
Delattre, Jean-Yves
Sanson, Marc
Lomonte, Patrick
Poncet, Delphine
Verrelle, Pierre
Charbonneau, Michel
author_sort Grandin, Nathalie
collection PubMed
description All cancer cells need to maintain functional telomeres to sustain continuous cell division and proliferation. In human diffuse gliomas, functional telomeres are maintained due either to reactivation of telomerase expression, the main pathway in most cancer types, or to activation of a mechanism called the alternative lengthening of telomeres (ALT). The presence of IDH1/2 mutations (IDH-mutant) together with loss of ATRX expression (ATRX-lost) are frequently associated with ALT in diffuse gliomas. However, detection of ALT, and a fortiori its quantification, are rarely, if ever, measured in neuropathology laboratories. We measured the level of ALT activity using the previously described quantitative “C-circle” assay and analyzed it in a well characterized cohort of 104 IDH-mutant and ATRX-lost adult diffuse gliomas. We report that in IDH-mutant ATRX-lost anaplastic astrocytomas, the intensity of ALT was inversely correlated with age (p < 0.001), the younger the patient, the higher the intensity of ALT. Strikingly, glioblastomas having progressed from anaplastic astrocytomas did not exhibit this correlation. ALT activity level in the tumor did not depend on telomere length in healthy tissue cells from the same patient. In summary, we have uncovered the existence, in anaplastic astrocytomas but not in glioblastomas with the same IDH and ATRX mutations, of a correlation between patient age and the level of activity of ALT, a telomerase-independent pathway of telomere maintenance.
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spelling pubmed-68425232019-11-14 The level of activity of the alternative lengthening of telomeres correlates with patient age in IDH-mutant ATRX-loss-of-expression anaplastic astrocytomas Grandin, Nathalie Pereira, Bruno Cohen, Camille Billard, Pauline Dehais, Caroline Carpentier, Catherine Idbaih, Ahmed Bielle, Franck Ducray, François Figarella-Branger, Dominique Delattre, Jean-Yves Sanson, Marc Lomonte, Patrick Poncet, Delphine Verrelle, Pierre Charbonneau, Michel Acta Neuropathol Commun Research All cancer cells need to maintain functional telomeres to sustain continuous cell division and proliferation. In human diffuse gliomas, functional telomeres are maintained due either to reactivation of telomerase expression, the main pathway in most cancer types, or to activation of a mechanism called the alternative lengthening of telomeres (ALT). The presence of IDH1/2 mutations (IDH-mutant) together with loss of ATRX expression (ATRX-lost) are frequently associated with ALT in diffuse gliomas. However, detection of ALT, and a fortiori its quantification, are rarely, if ever, measured in neuropathology laboratories. We measured the level of ALT activity using the previously described quantitative “C-circle” assay and analyzed it in a well characterized cohort of 104 IDH-mutant and ATRX-lost adult diffuse gliomas. We report that in IDH-mutant ATRX-lost anaplastic astrocytomas, the intensity of ALT was inversely correlated with age (p < 0.001), the younger the patient, the higher the intensity of ALT. Strikingly, glioblastomas having progressed from anaplastic astrocytomas did not exhibit this correlation. ALT activity level in the tumor did not depend on telomere length in healthy tissue cells from the same patient. In summary, we have uncovered the existence, in anaplastic astrocytomas but not in glioblastomas with the same IDH and ATRX mutations, of a correlation between patient age and the level of activity of ALT, a telomerase-independent pathway of telomere maintenance. BioMed Central 2019-11-09 /pmc/articles/PMC6842523/ /pubmed/31706351 http://dx.doi.org/10.1186/s40478-019-0833-0 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Grandin, Nathalie
Pereira, Bruno
Cohen, Camille
Billard, Pauline
Dehais, Caroline
Carpentier, Catherine
Idbaih, Ahmed
Bielle, Franck
Ducray, François
Figarella-Branger, Dominique
Delattre, Jean-Yves
Sanson, Marc
Lomonte, Patrick
Poncet, Delphine
Verrelle, Pierre
Charbonneau, Michel
The level of activity of the alternative lengthening of telomeres correlates with patient age in IDH-mutant ATRX-loss-of-expression anaplastic astrocytomas
title The level of activity of the alternative lengthening of telomeres correlates with patient age in IDH-mutant ATRX-loss-of-expression anaplastic astrocytomas
title_full The level of activity of the alternative lengthening of telomeres correlates with patient age in IDH-mutant ATRX-loss-of-expression anaplastic astrocytomas
title_fullStr The level of activity of the alternative lengthening of telomeres correlates with patient age in IDH-mutant ATRX-loss-of-expression anaplastic astrocytomas
title_full_unstemmed The level of activity of the alternative lengthening of telomeres correlates with patient age in IDH-mutant ATRX-loss-of-expression anaplastic astrocytomas
title_short The level of activity of the alternative lengthening of telomeres correlates with patient age in IDH-mutant ATRX-loss-of-expression anaplastic astrocytomas
title_sort level of activity of the alternative lengthening of telomeres correlates with patient age in idh-mutant atrx-loss-of-expression anaplastic astrocytomas
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6842523/
https://www.ncbi.nlm.nih.gov/pubmed/31706351
http://dx.doi.org/10.1186/s40478-019-0833-0
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