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Persistent STAG2 mutation despite multimodal therapy in recurrent pediatric glioblastoma
Similar to their adult counterparts, the prognosis for pediatric patients with high-grade gliomas remains poor. At time of recurrence, treatment options are limited and remain without consensus. This report describes the genetic findings, obtained from whole-exome sequencing of a pediatric patient w...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7264170/ https://www.ncbi.nlm.nih.gov/pubmed/32528726 http://dx.doi.org/10.1038/s41525-020-0130-7 |
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author | Hong, Christopher S. Vasquez, Juan C. Kundishora, Adam J. Elsamadicy, Aladine A. Beckta, Jason M. Sule, Amrita Marks, Asher M. Leelatian, Nalin Huttner, Anita Bindra, Ranjit S. DiLuna, Michael L. Kahle, Kristopher T. Erson-Omay, E. Zeynep |
author_facet | Hong, Christopher S. Vasquez, Juan C. Kundishora, Adam J. Elsamadicy, Aladine A. Beckta, Jason M. Sule, Amrita Marks, Asher M. Leelatian, Nalin Huttner, Anita Bindra, Ranjit S. DiLuna, Michael L. Kahle, Kristopher T. Erson-Omay, E. Zeynep |
author_sort | Hong, Christopher S. |
collection | PubMed |
description | Similar to their adult counterparts, the prognosis for pediatric patients with high-grade gliomas remains poor. At time of recurrence, treatment options are limited and remain without consensus. This report describes the genetic findings, obtained from whole-exome sequencing of a pediatric patient with glioblastoma who underwent multiple surgical resections and treatment with standard chemoradiation, as well as a novel recombinant poliovirus vaccine therapy. Strikingly, despite the variety of treatments, there was persistence of a tumor clone, characterized by a deleterious STAG2 mutation, whose deficiency in preclinical studies can cause aneuploidy and aberrant mitotic progression, but remains understudied in the clinical setting. There was near elimination of an EGFR mutated and amplified tumor clone after gross total resection, standard chemoradiation, and poliovirus therapy, followed by the emergence of a persistently STAG2 mutated clone, with rare mutations in PTPN11 and BRAF, the latter composed of a novel deleterious mutation previously not reported in pediatric glioblastoma (p.D594G). This was accompanied by a mutation signature shift towards one characterized by increased DNA damage repair defects, consistent with the known underlying STAG2 deficiency. As such, this case represents a novel report following the clinical and genetic progression of a STAG2 mutated glioblastoma, including treatment with a novel and emerging immunotherapy. Although STAG2 deficiency comprises only a small subset of gliomas, this case adds clinical evidence to existing preclinical data supporting a role for STAG2 mutations in gliomagenesis and resistance to standard therapies. |
format | Online Article Text |
id | pubmed-7264170 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-72641702020-06-10 Persistent STAG2 mutation despite multimodal therapy in recurrent pediatric glioblastoma Hong, Christopher S. Vasquez, Juan C. Kundishora, Adam J. Elsamadicy, Aladine A. Beckta, Jason M. Sule, Amrita Marks, Asher M. Leelatian, Nalin Huttner, Anita Bindra, Ranjit S. DiLuna, Michael L. Kahle, Kristopher T. Erson-Omay, E. Zeynep NPJ Genom Med Case Report Similar to their adult counterparts, the prognosis for pediatric patients with high-grade gliomas remains poor. At time of recurrence, treatment options are limited and remain without consensus. This report describes the genetic findings, obtained from whole-exome sequencing of a pediatric patient with glioblastoma who underwent multiple surgical resections and treatment with standard chemoradiation, as well as a novel recombinant poliovirus vaccine therapy. Strikingly, despite the variety of treatments, there was persistence of a tumor clone, characterized by a deleterious STAG2 mutation, whose deficiency in preclinical studies can cause aneuploidy and aberrant mitotic progression, but remains understudied in the clinical setting. There was near elimination of an EGFR mutated and amplified tumor clone after gross total resection, standard chemoradiation, and poliovirus therapy, followed by the emergence of a persistently STAG2 mutated clone, with rare mutations in PTPN11 and BRAF, the latter composed of a novel deleterious mutation previously not reported in pediatric glioblastoma (p.D594G). This was accompanied by a mutation signature shift towards one characterized by increased DNA damage repair defects, consistent with the known underlying STAG2 deficiency. As such, this case represents a novel report following the clinical and genetic progression of a STAG2 mutated glioblastoma, including treatment with a novel and emerging immunotherapy. Although STAG2 deficiency comprises only a small subset of gliomas, this case adds clinical evidence to existing preclinical data supporting a role for STAG2 mutations in gliomagenesis and resistance to standard therapies. Nature Publishing Group UK 2020-06-01 /pmc/articles/PMC7264170/ /pubmed/32528726 http://dx.doi.org/10.1038/s41525-020-0130-7 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Case Report Hong, Christopher S. Vasquez, Juan C. Kundishora, Adam J. Elsamadicy, Aladine A. Beckta, Jason M. Sule, Amrita Marks, Asher M. Leelatian, Nalin Huttner, Anita Bindra, Ranjit S. DiLuna, Michael L. Kahle, Kristopher T. Erson-Omay, E. Zeynep Persistent STAG2 mutation despite multimodal therapy in recurrent pediatric glioblastoma |
title | Persistent STAG2 mutation despite multimodal therapy in recurrent pediatric glioblastoma |
title_full | Persistent STAG2 mutation despite multimodal therapy in recurrent pediatric glioblastoma |
title_fullStr | Persistent STAG2 mutation despite multimodal therapy in recurrent pediatric glioblastoma |
title_full_unstemmed | Persistent STAG2 mutation despite multimodal therapy in recurrent pediatric glioblastoma |
title_short | Persistent STAG2 mutation despite multimodal therapy in recurrent pediatric glioblastoma |
title_sort | persistent stag2 mutation despite multimodal therapy in recurrent pediatric glioblastoma |
topic | Case Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7264170/ https://www.ncbi.nlm.nih.gov/pubmed/32528726 http://dx.doi.org/10.1038/s41525-020-0130-7 |
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