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BIOL-15. PATIENT-DERIVED XENOGRAFTS OF MATCHED PRIMARY-RECURRENT PEDIATRIC BRAIN TUMORS AS A RESOURCE FOR IDENTIFYING THERAPY RESISTANCE PROFILES

Tumor recurrence developing from therapy resistance, immune escape and metastasis is the leading cause of death of malignant pediatric brain tumors. By studying paired primary-recurrent patient samples we previously identified significant accumulation of SOX9-positive cells in Group 3 medulloblastom...

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Autores principales: Zhao, Miao, Olsen, Thale, Bergström, Tobias, Rosén, Gabriela, Dalmo, Erika, Vikström, Elin, Larsson, Ida, Lin, Tina, Sundström, Anders, Holmberg, Karl, Weishaupt, Holger, Nelander, Sven, Giraud, Geraldine, Swartling, Fredrik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10260138/
http://dx.doi.org/10.1093/neuonc/noad073.034
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author Zhao, Miao
Olsen, Thale
Bergström, Tobias
Rosén, Gabriela
Dalmo, Erika
Vikström, Elin
Larsson, Ida
Lin, Tina
Sundström, Anders
Holmberg, Karl
Weishaupt, Holger
Nelander, Sven
Giraud, Geraldine
Swartling, Fredrik
author_facet Zhao, Miao
Olsen, Thale
Bergström, Tobias
Rosén, Gabriela
Dalmo, Erika
Vikström, Elin
Larsson, Ida
Lin, Tina
Sundström, Anders
Holmberg, Karl
Weishaupt, Holger
Nelander, Sven
Giraud, Geraldine
Swartling, Fredrik
author_sort Zhao, Miao
collection PubMed
description Tumor recurrence developing from therapy resistance, immune escape and metastasis is the leading cause of death of malignant pediatric brain tumors. By studying paired primary-recurrent patient samples we previously identified significant accumulation of SOX9-positive cells in Group 3 medulloblastoma that was similarly induced following long-term irradiation in transgenic mouse models of MYC-induced medulloblastoma. To follow relapse biology in malignant pediatric brain tumors at the single cell level we have established patient-derived xenografts (PDXs) from a number of matched primary-relapse samples, including pediatric high-grade glioma, medulloblastoma and ependymoma profiled with DNA methylation analysis. We next used scRNA-Seq to identify clones with particular expression of genes and distinct signaling pathways enriched in recurrent tumor cells as compared to their matched primary tumor cells. We further used a lentivirus-based barcoding strategy coupled to scRNA-Seq to study the molecular evolution of cell clones arising from genetically modified mouse models and PDXs that survive long-term fractionated irradiation, cisplatin or temozolomide treatment in vitro and in vivo. By using computational modeling we identified means of specific targeting of recurrent cells that could be of potential use in future treatments for patients affected by fatal relapses. Our results suggest that pediatric brain tumors of distinct tumor entities use different ways to acquire therapy resistance in patients which is often coupled to an expansion of clones that are developing therapy-induced resistance.
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spelling pubmed-102601382023-06-13 BIOL-15. PATIENT-DERIVED XENOGRAFTS OF MATCHED PRIMARY-RECURRENT PEDIATRIC BRAIN TUMORS AS A RESOURCE FOR IDENTIFYING THERAPY RESISTANCE PROFILES Zhao, Miao Olsen, Thale Bergström, Tobias Rosén, Gabriela Dalmo, Erika Vikström, Elin Larsson, Ida Lin, Tina Sundström, Anders Holmberg, Karl Weishaupt, Holger Nelander, Sven Giraud, Geraldine Swartling, Fredrik Neuro Oncol Final Category: Basic Biology/Stem Cells/Models - BIOL Tumor recurrence developing from therapy resistance, immune escape and metastasis is the leading cause of death of malignant pediatric brain tumors. By studying paired primary-recurrent patient samples we previously identified significant accumulation of SOX9-positive cells in Group 3 medulloblastoma that was similarly induced following long-term irradiation in transgenic mouse models of MYC-induced medulloblastoma. To follow relapse biology in malignant pediatric brain tumors at the single cell level we have established patient-derived xenografts (PDXs) from a number of matched primary-relapse samples, including pediatric high-grade glioma, medulloblastoma and ependymoma profiled with DNA methylation analysis. We next used scRNA-Seq to identify clones with particular expression of genes and distinct signaling pathways enriched in recurrent tumor cells as compared to their matched primary tumor cells. We further used a lentivirus-based barcoding strategy coupled to scRNA-Seq to study the molecular evolution of cell clones arising from genetically modified mouse models and PDXs that survive long-term fractionated irradiation, cisplatin or temozolomide treatment in vitro and in vivo. By using computational modeling we identified means of specific targeting of recurrent cells that could be of potential use in future treatments for patients affected by fatal relapses. Our results suggest that pediatric brain tumors of distinct tumor entities use different ways to acquire therapy resistance in patients which is often coupled to an expansion of clones that are developing therapy-induced resistance. Oxford University Press 2023-06-12 /pmc/articles/PMC10260138/ http://dx.doi.org/10.1093/neuonc/noad073.034 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (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 Final Category: Basic Biology/Stem Cells/Models - BIOL
Zhao, Miao
Olsen, Thale
Bergström, Tobias
Rosén, Gabriela
Dalmo, Erika
Vikström, Elin
Larsson, Ida
Lin, Tina
Sundström, Anders
Holmberg, Karl
Weishaupt, Holger
Nelander, Sven
Giraud, Geraldine
Swartling, Fredrik
BIOL-15. PATIENT-DERIVED XENOGRAFTS OF MATCHED PRIMARY-RECURRENT PEDIATRIC BRAIN TUMORS AS A RESOURCE FOR IDENTIFYING THERAPY RESISTANCE PROFILES
title BIOL-15. PATIENT-DERIVED XENOGRAFTS OF MATCHED PRIMARY-RECURRENT PEDIATRIC BRAIN TUMORS AS A RESOURCE FOR IDENTIFYING THERAPY RESISTANCE PROFILES
title_full BIOL-15. PATIENT-DERIVED XENOGRAFTS OF MATCHED PRIMARY-RECURRENT PEDIATRIC BRAIN TUMORS AS A RESOURCE FOR IDENTIFYING THERAPY RESISTANCE PROFILES
title_fullStr BIOL-15. PATIENT-DERIVED XENOGRAFTS OF MATCHED PRIMARY-RECURRENT PEDIATRIC BRAIN TUMORS AS A RESOURCE FOR IDENTIFYING THERAPY RESISTANCE PROFILES
title_full_unstemmed BIOL-15. PATIENT-DERIVED XENOGRAFTS OF MATCHED PRIMARY-RECURRENT PEDIATRIC BRAIN TUMORS AS A RESOURCE FOR IDENTIFYING THERAPY RESISTANCE PROFILES
title_short BIOL-15. PATIENT-DERIVED XENOGRAFTS OF MATCHED PRIMARY-RECURRENT PEDIATRIC BRAIN TUMORS AS A RESOURCE FOR IDENTIFYING THERAPY RESISTANCE PROFILES
title_sort biol-15. patient-derived xenografts of matched primary-recurrent pediatric brain tumors as a resource for identifying therapy resistance profiles
topic Final Category: Basic Biology/Stem Cells/Models - BIOL
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10260138/
http://dx.doi.org/10.1093/neuonc/noad073.034
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