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Chromosome 1q gain and tenascin-C expression are candidate markers to define different risk groups in pediatric posterior fossa ependymoma

Intracranial classic (WHO grade II) and anaplastic (WHO grade III) ependymomas are among the most common tumors in pediatric patients and have due to frequent recurrences and late relapses a relatively poor outcome. The impact of histopathological grading on patient outcome is controversial and ther...

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Autores principales: Araki, Asuka, Chocholous, Monika, Gojo, Johannes, Dorfer, Christian, Czech, Thomas, Heinzl, Harald, Dieckmann, Karin, Ambros, Inge M., Ambros, Peter F., Slavc, Irene, Haberler, Christine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4994287/
https://www.ncbi.nlm.nih.gov/pubmed/27550150
http://dx.doi.org/10.1186/s40478-016-0349-9
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author Araki, Asuka
Chocholous, Monika
Gojo, Johannes
Dorfer, Christian
Czech, Thomas
Heinzl, Harald
Dieckmann, Karin
Ambros, Inge M.
Ambros, Peter F.
Slavc, Irene
Haberler, Christine
author_facet Araki, Asuka
Chocholous, Monika
Gojo, Johannes
Dorfer, Christian
Czech, Thomas
Heinzl, Harald
Dieckmann, Karin
Ambros, Inge M.
Ambros, Peter F.
Slavc, Irene
Haberler, Christine
author_sort Araki, Asuka
collection PubMed
description Intracranial classic (WHO grade II) and anaplastic (WHO grade III) ependymomas are among the most common tumors in pediatric patients and have due to frequent recurrences and late relapses a relatively poor outcome. The impact of histopathological grading on patient outcome is controversial and therefore, molecular prognostic and predictive markers are needed to improve patient outcome. To date, the most promising candidate marker is chromosome 1q gain, which has been associated in independent studies with adverse outcome. Furthermore, gene expression and methylation profiles revealed distinct molecular subgroups in the supratentorial and posterior fossa (PF) compartment and Laminin alpha-2 (LAMA2) and Neural Epidermal Growth Factor Like-2 (NELL2) were suggested as surrogate markers for the two PF subgroups PF-EPN-A and PF-EPN-B. PF-EPN-A tumors were also characterized by tenascin-C (TNC) expression and tenascin-C has been suggested as candidate gene on 9q, involved in tumor progression. Therefore, we have analyzed the status of chromosome 1q, TNC, LAMA2, and NELL2 expression in a series of pediatric PF ependymomas in terms of their frequency, associations among themselves, and clinical parameters, as well as their prognostic impact. We confirm the negative prognostic impact of 1q gain and TNC expression and could classify PF ependymomas by these two markers into three molecular subgroups. Tumors with combined 1q gain and TNC expression had the poorest, tumors without 1q gain and TNC expression had a favorable and TNC positive 1q non-gained cases had an intermediate outcome. We found also differences in age and tumor grade in the three subgroups and thus, provide evidence that PF pediatric ependymomas can be divided by chromosome 1q status and TNC expression in three molecular subgroups with distinct clinico-pathological features. These analyses require only few amounts of tumor tissue, are broadly available in the routine clinical neuropathological setting and thus, could be used in further therapy trials to optimize treatment of ependymoma patients.
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spelling pubmed-49942872016-08-24 Chromosome 1q gain and tenascin-C expression are candidate markers to define different risk groups in pediatric posterior fossa ependymoma Araki, Asuka Chocholous, Monika Gojo, Johannes Dorfer, Christian Czech, Thomas Heinzl, Harald Dieckmann, Karin Ambros, Inge M. Ambros, Peter F. Slavc, Irene Haberler, Christine Acta Neuropathol Commun Research Intracranial classic (WHO grade II) and anaplastic (WHO grade III) ependymomas are among the most common tumors in pediatric patients and have due to frequent recurrences and late relapses a relatively poor outcome. The impact of histopathological grading on patient outcome is controversial and therefore, molecular prognostic and predictive markers are needed to improve patient outcome. To date, the most promising candidate marker is chromosome 1q gain, which has been associated in independent studies with adverse outcome. Furthermore, gene expression and methylation profiles revealed distinct molecular subgroups in the supratentorial and posterior fossa (PF) compartment and Laminin alpha-2 (LAMA2) and Neural Epidermal Growth Factor Like-2 (NELL2) were suggested as surrogate markers for the two PF subgroups PF-EPN-A and PF-EPN-B. PF-EPN-A tumors were also characterized by tenascin-C (TNC) expression and tenascin-C has been suggested as candidate gene on 9q, involved in tumor progression. Therefore, we have analyzed the status of chromosome 1q, TNC, LAMA2, and NELL2 expression in a series of pediatric PF ependymomas in terms of their frequency, associations among themselves, and clinical parameters, as well as their prognostic impact. We confirm the negative prognostic impact of 1q gain and TNC expression and could classify PF ependymomas by these two markers into three molecular subgroups. Tumors with combined 1q gain and TNC expression had the poorest, tumors without 1q gain and TNC expression had a favorable and TNC positive 1q non-gained cases had an intermediate outcome. We found also differences in age and tumor grade in the three subgroups and thus, provide evidence that PF pediatric ependymomas can be divided by chromosome 1q status and TNC expression in three molecular subgroups with distinct clinico-pathological features. These analyses require only few amounts of tumor tissue, are broadly available in the routine clinical neuropathological setting and thus, could be used in further therapy trials to optimize treatment of ependymoma patients. BioMed Central 2016-08-22 /pmc/articles/PMC4994287/ /pubmed/27550150 http://dx.doi.org/10.1186/s40478-016-0349-9 Text en © The Author(s). 2016 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
Araki, Asuka
Chocholous, Monika
Gojo, Johannes
Dorfer, Christian
Czech, Thomas
Heinzl, Harald
Dieckmann, Karin
Ambros, Inge M.
Ambros, Peter F.
Slavc, Irene
Haberler, Christine
Chromosome 1q gain and tenascin-C expression are candidate markers to define different risk groups in pediatric posterior fossa ependymoma
title Chromosome 1q gain and tenascin-C expression are candidate markers to define different risk groups in pediatric posterior fossa ependymoma
title_full Chromosome 1q gain and tenascin-C expression are candidate markers to define different risk groups in pediatric posterior fossa ependymoma
title_fullStr Chromosome 1q gain and tenascin-C expression are candidate markers to define different risk groups in pediatric posterior fossa ependymoma
title_full_unstemmed Chromosome 1q gain and tenascin-C expression are candidate markers to define different risk groups in pediatric posterior fossa ependymoma
title_short Chromosome 1q gain and tenascin-C expression are candidate markers to define different risk groups in pediatric posterior fossa ependymoma
title_sort chromosome 1q gain and tenascin-c expression are candidate markers to define different risk groups in pediatric posterior fossa ependymoma
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4994287/
https://www.ncbi.nlm.nih.gov/pubmed/27550150
http://dx.doi.org/10.1186/s40478-016-0349-9
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