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EPEN-06. CELL ECOSYSTEM AND SIGNALING PATHWAYS OF PRIMARY AND METASTATIC PEDIATRIC POSTERIOR FOSSA EPENDYMOMA
Childhood ependymoma is a cancer of the central nervous system with a chronic relapsing pattern. In children, 90% of ependymal tumors occur intracranially where prognosis is grim. Standard care for this disease includes surgical resection followed by radiation. Despite several clinical trials, adjuv...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168247/ http://dx.doi.org/10.1093/neuonc/noab090.056 |
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author | Aubin, Rachael Troisi, Emma Alghalith, Adam Nasrallah, MacLean Santi, Mariarita Camara, Pablo |
author_facet | Aubin, Rachael Troisi, Emma Alghalith, Adam Nasrallah, MacLean Santi, Mariarita Camara, Pablo |
author_sort | Aubin, Rachael |
collection | PubMed |
description | Childhood ependymoma is a cancer of the central nervous system with a chronic relapsing pattern. In children, 90% of ependymal tumors occur intracranially where prognosis is grim. Standard care for this disease includes surgical resection followed by radiation. Despite several clinical trials, adjuvant chemotherapies have yet to extend patient survival, highlighting a need for more effective treatment options. Ependymal tumors have been stratified into nine molecular subgroups based on their DNA methylation profile. The most prevalent and aggressive pediatric subgroup is known as posterior fossa ependymoma type A (PFA) which represents approximately 60% of pediatric cases and has a 5-year progression free survival rate of 30%. Whole genome sequencing studies have revealed that PFA tumors rarely harbor recurrent mutations. To inform the potential development of new treatment options for this disease, we sought to decipher the specific mechanisms leading to the tumorigenesis, progression, and metastasis of PFA tumors. By means of single-nuclei RNA-seq and an array of computational methods, we show that the expression profile of PFA tumor cells recapitulate the developmental lineages of radial glia in neurogenic niches, and is consistent with an origin in LGR+ stem cells and a pro-inflammatory environment. In addition, our analysis reveals the abundance of a mesenchymal cell population expressing TGF-β signaling, reactive gliosis, and hypoxia-related genes in distal metastases from PFA tumors. Taken together, our results uncover the cell ecosystem of pediatric posterior fossa ependymoma and identify WNT/β-catenin and TGF-β signaling as candidate drivers of tumorigenesis for this cancer. |
format | Online Article Text |
id | pubmed-8168247 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-81682472021-06-02 EPEN-06. CELL ECOSYSTEM AND SIGNALING PATHWAYS OF PRIMARY AND METASTATIC PEDIATRIC POSTERIOR FOSSA EPENDYMOMA Aubin, Rachael Troisi, Emma Alghalith, Adam Nasrallah, MacLean Santi, Mariarita Camara, Pablo Neuro Oncol Ependymoma Childhood ependymoma is a cancer of the central nervous system with a chronic relapsing pattern. In children, 90% of ependymal tumors occur intracranially where prognosis is grim. Standard care for this disease includes surgical resection followed by radiation. Despite several clinical trials, adjuvant chemotherapies have yet to extend patient survival, highlighting a need for more effective treatment options. Ependymal tumors have been stratified into nine molecular subgroups based on their DNA methylation profile. The most prevalent and aggressive pediatric subgroup is known as posterior fossa ependymoma type A (PFA) which represents approximately 60% of pediatric cases and has a 5-year progression free survival rate of 30%. Whole genome sequencing studies have revealed that PFA tumors rarely harbor recurrent mutations. To inform the potential development of new treatment options for this disease, we sought to decipher the specific mechanisms leading to the tumorigenesis, progression, and metastasis of PFA tumors. By means of single-nuclei RNA-seq and an array of computational methods, we show that the expression profile of PFA tumor cells recapitulate the developmental lineages of radial glia in neurogenic niches, and is consistent with an origin in LGR+ stem cells and a pro-inflammatory environment. In addition, our analysis reveals the abundance of a mesenchymal cell population expressing TGF-β signaling, reactive gliosis, and hypoxia-related genes in distal metastases from PFA tumors. Taken together, our results uncover the cell ecosystem of pediatric posterior fossa ependymoma and identify WNT/β-catenin and TGF-β signaling as candidate drivers of tumorigenesis for this cancer. Oxford University Press 2021-06-01 /pmc/articles/PMC8168247/ http://dx.doi.org/10.1093/neuonc/noab090.056 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. https://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/ (https://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 | Ependymoma Aubin, Rachael Troisi, Emma Alghalith, Adam Nasrallah, MacLean Santi, Mariarita Camara, Pablo EPEN-06. CELL ECOSYSTEM AND SIGNALING PATHWAYS OF PRIMARY AND METASTATIC PEDIATRIC POSTERIOR FOSSA EPENDYMOMA |
title | EPEN-06. CELL ECOSYSTEM AND SIGNALING PATHWAYS OF PRIMARY AND METASTATIC PEDIATRIC POSTERIOR FOSSA EPENDYMOMA |
title_full | EPEN-06. CELL ECOSYSTEM AND SIGNALING PATHWAYS OF PRIMARY AND METASTATIC PEDIATRIC POSTERIOR FOSSA EPENDYMOMA |
title_fullStr | EPEN-06. CELL ECOSYSTEM AND SIGNALING PATHWAYS OF PRIMARY AND METASTATIC PEDIATRIC POSTERIOR FOSSA EPENDYMOMA |
title_full_unstemmed | EPEN-06. CELL ECOSYSTEM AND SIGNALING PATHWAYS OF PRIMARY AND METASTATIC PEDIATRIC POSTERIOR FOSSA EPENDYMOMA |
title_short | EPEN-06. CELL ECOSYSTEM AND SIGNALING PATHWAYS OF PRIMARY AND METASTATIC PEDIATRIC POSTERIOR FOSSA EPENDYMOMA |
title_sort | epen-06. cell ecosystem and signaling pathways of primary and metastatic pediatric posterior fossa ependymoma |
topic | Ependymoma |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168247/ http://dx.doi.org/10.1093/neuonc/noab090.056 |
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