The level of activity of the alternative lengthening of telomeres correlates with patient age in IDH-mutant ATRX-loss-of-expression anaplastic astrocytomas
Abstract 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 mecha...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-11-01
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| Series: | Acta Neuropathologica Communications |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s40478-019-0833-0 |
| _version_ | 1818256574982914048 |
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| author | Nathalie Grandin Bruno Pereira Camille Cohen Pauline Billard Caroline Dehais Catherine Carpentier Ahmed Idbaih Franck Bielle François Ducray Dominique Figarella-Branger Jean-Yves Delattre Marc Sanson Patrick Lomonte Delphine Poncet Pierre Verrelle Michel Charbonneau POLA network |
| author_facet | Nathalie Grandin Bruno Pereira Camille Cohen Pauline Billard Caroline Dehais Catherine Carpentier Ahmed Idbaih Franck Bielle François Ducray Dominique Figarella-Branger Jean-Yves Delattre Marc Sanson Patrick Lomonte Delphine Poncet Pierre Verrelle Michel Charbonneau POLA network |
| author_sort | Nathalie Grandin |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-12T17:29:56Z |
| format | Article |
| id | doaj.art-033e5e02097745a599971cc3a45d4b83 |
| institution | Directory Open Access Journal |
| issn | 2051-5960 |
| language | English |
| last_indexed | 2024-12-12T17:29:56Z |
| publishDate | 2019-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Acta Neuropathologica Communications |
| spelling | doaj.art-033e5e02097745a599971cc3a45d4b832022-12-22T00:17:24ZengBMCActa Neuropathologica Communications2051-59602019-11-017111310.1186/s40478-019-0833-0The level of activity of the alternative lengthening of telomeres correlates with patient age in IDH-mutant ATRX-loss-of-expression anaplastic astrocytomasNathalie Grandin0Bruno Pereira1Camille Cohen2Pauline Billard3Caroline Dehais4Catherine Carpentier5Ahmed Idbaih6Franck Bielle7François Ducray8Dominique Figarella-Branger9Jean-Yves Delattre10Marc Sanson11Patrick Lomonte12Delphine Poncet13Pierre Verrelle14Michel Charbonneau15POLA networkLaboratoire GReD, CNRS UMR6293, INSERM U1103, Faculty of MedicineCHU Clermont-Ferrand, Biostatistics unit, DRCIUniversité de Lyon, Université Claude Bernard Lyon 1, CNRS UMR 5310, INSERM U 1217, LabEx DEVweCAN, Institut NeuroMyoGène (INMG)Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Centre de recherche en cancérologie de LyonAP-HP, Groupe Hospitalier Pitié-Salpêtrière Charles Foix, Service de neurologie 2-MazarinSorbonne Université, INSERM, CNRS, UMR S1127, Institut du Cerveau et de la Moelle épinière, ICMAP-HP, Groupe Hospitalier Pitié-Salpêtrière Charles Foix, Service de neurologie 2-MazarinSorbonne Université, INSERM, CNRS, UMR S1127, Institut du Cerveau et de la Moelle épinière, ICMHospices Civils de Lyon, Hôpital Pierre Wertheimer, Service de Neuro-oncologieAPHM, Hôpital de la Timone, Service d’Anatomie Pathologique et de NeuropathologieAP-HP, Groupe Hospitalier Pitié-Salpêtrière Charles Foix, Service de neurologie 2-MazarinAP-HP, Groupe Hospitalier Pitié-Salpêtrière Charles Foix, Service de neurologie 2-MazarinUniversité de Lyon, Université Claude Bernard Lyon 1, CNRS UMR 5310, INSERM U 1217, LabEx DEVweCAN, Institut NeuroMyoGène (INMG)Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Centre de recherche en cancérologie de LyonUniversité Clermont AuvergneLaboratoire GReD, CNRS UMR6293, INSERM U1103, Faculty of MedicineAbstract 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.http://link.springer.com/article/10.1186/s40478-019-0833-0Anaplastic astrocytomaSecondary glioblastomaAlternative lengthening of telomeresIDH1/2 mutationsATRX loss of expression |
| spellingShingle | Nathalie Grandin Bruno Pereira Camille Cohen Pauline Billard Caroline Dehais Catherine Carpentier Ahmed Idbaih Franck Bielle François Ducray Dominique Figarella-Branger Jean-Yves Delattre Marc Sanson Patrick Lomonte Delphine Poncet Pierre Verrelle Michel Charbonneau POLA network The level of activity of the alternative lengthening of telomeres correlates with patient age in IDH-mutant ATRX-loss-of-expression anaplastic astrocytomas Acta Neuropathologica Communications Anaplastic astrocytoma Secondary glioblastoma Alternative lengthening of telomeres IDH1/2 mutations ATRX loss of expression |
| 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 | Anaplastic astrocytoma Secondary glioblastoma Alternative lengthening of telomeres IDH1/2 mutations ATRX loss of expression |
| url | http://link.springer.com/article/10.1186/s40478-019-0833-0 |
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