Cargando…
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...
Autores principales: | , , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1783468058747076608 |
---|---|
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. |
format | Online Article Text |
id | pubmed-6842523 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT grandinnathalie thelevelofactivityofthealternativelengtheningoftelomerescorrelateswithpatientageinidhmutantatrxlossofexpressionanaplasticastrocytomas AT pereirabruno thelevelofactivityofthealternativelengtheningoftelomerescorrelateswithpatientageinidhmutantatrxlossofexpressionanaplasticastrocytomas AT cohencamille thelevelofactivityofthealternativelengtheningoftelomerescorrelateswithpatientageinidhmutantatrxlossofexpressionanaplasticastrocytomas AT billardpauline thelevelofactivityofthealternativelengtheningoftelomerescorrelateswithpatientageinidhmutantatrxlossofexpressionanaplasticastrocytomas AT dehaiscaroline thelevelofactivityofthealternativelengtheningoftelomerescorrelateswithpatientageinidhmutantatrxlossofexpressionanaplasticastrocytomas AT carpentiercatherine thelevelofactivityofthealternativelengtheningoftelomerescorrelateswithpatientageinidhmutantatrxlossofexpressionanaplasticastrocytomas AT idbaihahmed thelevelofactivityofthealternativelengtheningoftelomerescorrelateswithpatientageinidhmutantatrxlossofexpressionanaplasticastrocytomas AT biellefranck thelevelofactivityofthealternativelengtheningoftelomerescorrelateswithpatientageinidhmutantatrxlossofexpressionanaplasticastrocytomas AT ducrayfrancois thelevelofactivityofthealternativelengtheningoftelomerescorrelateswithpatientageinidhmutantatrxlossofexpressionanaplasticastrocytomas AT figarellabrangerdominique thelevelofactivityofthealternativelengtheningoftelomerescorrelateswithpatientageinidhmutantatrxlossofexpressionanaplasticastrocytomas AT delattrejeanyves thelevelofactivityofthealternativelengtheningoftelomerescorrelateswithpatientageinidhmutantatrxlossofexpressionanaplasticastrocytomas AT sansonmarc thelevelofactivityofthealternativelengtheningoftelomerescorrelateswithpatientageinidhmutantatrxlossofexpressionanaplasticastrocytomas AT lomontepatrick thelevelofactivityofthealternativelengtheningoftelomerescorrelateswithpatientageinidhmutantatrxlossofexpressionanaplasticastrocytomas AT poncetdelphine thelevelofactivityofthealternativelengtheningoftelomerescorrelateswithpatientageinidhmutantatrxlossofexpressionanaplasticastrocytomas AT verrellepierre thelevelofactivityofthealternativelengtheningoftelomerescorrelateswithpatientageinidhmutantatrxlossofexpressionanaplasticastrocytomas AT charbonneaumichel thelevelofactivityofthealternativelengtheningoftelomerescorrelateswithpatientageinidhmutantatrxlossofexpressionanaplasticastrocytomas AT thelevelofactivityofthealternativelengtheningoftelomerescorrelateswithpatientageinidhmutantatrxlossofexpressionanaplasticastrocytomas AT grandinnathalie levelofactivityofthealternativelengtheningoftelomerescorrelateswithpatientageinidhmutantatrxlossofexpressionanaplasticastrocytomas AT pereirabruno levelofactivityofthealternativelengtheningoftelomerescorrelateswithpatientageinidhmutantatrxlossofexpressionanaplasticastrocytomas AT cohencamille levelofactivityofthealternativelengtheningoftelomerescorrelateswithpatientageinidhmutantatrxlossofexpressionanaplasticastrocytomas AT billardpauline levelofactivityofthealternativelengtheningoftelomerescorrelateswithpatientageinidhmutantatrxlossofexpressionanaplasticastrocytomas AT dehaiscaroline levelofactivityofthealternativelengtheningoftelomerescorrelateswithpatientageinidhmutantatrxlossofexpressionanaplasticastrocytomas AT carpentiercatherine levelofactivityofthealternativelengtheningoftelomerescorrelateswithpatientageinidhmutantatrxlossofexpressionanaplasticastrocytomas AT idbaihahmed levelofactivityofthealternativelengtheningoftelomerescorrelateswithpatientageinidhmutantatrxlossofexpressionanaplasticastrocytomas AT biellefranck levelofactivityofthealternativelengtheningoftelomerescorrelateswithpatientageinidhmutantatrxlossofexpressionanaplasticastrocytomas AT ducrayfrancois levelofactivityofthealternativelengtheningoftelomerescorrelateswithpatientageinidhmutantatrxlossofexpressionanaplasticastrocytomas AT figarellabrangerdominique levelofactivityofthealternativelengtheningoftelomerescorrelateswithpatientageinidhmutantatrxlossofexpressionanaplasticastrocytomas AT delattrejeanyves levelofactivityofthealternativelengtheningoftelomerescorrelateswithpatientageinidhmutantatrxlossofexpressionanaplasticastrocytomas AT sansonmarc levelofactivityofthealternativelengtheningoftelomerescorrelateswithpatientageinidhmutantatrxlossofexpressionanaplasticastrocytomas AT lomontepatrick levelofactivityofthealternativelengtheningoftelomerescorrelateswithpatientageinidhmutantatrxlossofexpressionanaplasticastrocytomas AT poncetdelphine levelofactivityofthealternativelengtheningoftelomerescorrelateswithpatientageinidhmutantatrxlossofexpressionanaplasticastrocytomas AT verrellepierre levelofactivityofthealternativelengtheningoftelomerescorrelateswithpatientageinidhmutantatrxlossofexpressionanaplasticastrocytomas AT charbonneaumichel levelofactivityofthealternativelengtheningoftelomerescorrelateswithpatientageinidhmutantatrxlossofexpressionanaplasticastrocytomas AT levelofactivityofthealternativelengtheningoftelomerescorrelateswithpatientageinidhmutantatrxlossofexpressionanaplasticastrocytomas |