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Gliosarcoma vs. glioblastoma: a retrospective case series using molecular profiling

BACKGROUND: Gliosarcoma (GS) refers to the presence of mesenchymal differentiation (as seen using light microscopy) in the setting of glioblastoma (GB, an astrocytoma, WHO Grade 4). Although the same approach to treatment is typically adopted for GS and GB, there remains some debate as to whether GS...

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Autores principales: Dardis, Christopher, Donner, David, Sanai, Nader, Xiu, Joanne, Mittal, Sandeep, Michelhaugh, Sharon K., Pandey, Manjari, Kesari, Santosh, Heimberger, Amy B., Gatalica, Zoran, Korn, Michael W., Sumrall, Ashley L., Phuphanich, Surasak
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220715/
https://www.ncbi.nlm.nih.gov/pubmed/34162346
http://dx.doi.org/10.1186/s12883-021-02233-5
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author Dardis, Christopher
Donner, David
Sanai, Nader
Xiu, Joanne
Mittal, Sandeep
Michelhaugh, Sharon K.
Pandey, Manjari
Kesari, Santosh
Heimberger, Amy B.
Gatalica, Zoran
Korn, Michael W.
Sumrall, Ashley L.
Phuphanich, Surasak
author_facet Dardis, Christopher
Donner, David
Sanai, Nader
Xiu, Joanne
Mittal, Sandeep
Michelhaugh, Sharon K.
Pandey, Manjari
Kesari, Santosh
Heimberger, Amy B.
Gatalica, Zoran
Korn, Michael W.
Sumrall, Ashley L.
Phuphanich, Surasak
author_sort Dardis, Christopher
collection PubMed
description BACKGROUND: Gliosarcoma (GS) refers to the presence of mesenchymal differentiation (as seen using light microscopy) in the setting of glioblastoma (GB, an astrocytoma, WHO Grade 4). Although the same approach to treatment is typically adopted for GS and GB, there remains some debate as to whether GS should be considered a discrete pathological entity. Differences between these tumors have not been clearly established at the molecular level. METHODS: Patients with GS (n=48) or GB (n=1229) underwent molecular profiling (MP) with a pan-cancer panel of tests as part of their clinical care. The methods employed included next-generation sequencing (NGS) of DNA and RNA, copy number variation (CNV) of DNA and immunohistochemistry (IHC). The MP comprised 1153 tests in total, although results for each test were not available for every tumor profiled. We analyzed this data retrospectively in order to determine if our results were in keeping with what is known about the pathogenesis of GS by contrast with GB. We also sought novel associations between the MP and GS vs. GB which might improve our understanding of pathogenesis of GS. RESULTS: Potentially meaningful associations (p<0.1, Fisher’s exact test (FET)) were found for 14 of these tests in GS vs. GB. A novel finding was higher levels of proteins mediating immuno-evasion (PD-1, PD-L1) in GS. All of the differences we observed have been associated with epithelial-to-mesenchymal transition (EMT) in other tumor types. Many of the changes we saw in GS are novel in the setting of glial tumors, including copy number amplification in LYL1 and mutations in PTPN11. CONCLUSIONS: GS shows certain characteristics of EMT, by contrast with GB. Treatments targeting immuno-evasion may be of greater therapeutic value in GS relative to GB. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at (10.1186/s12883-021-02233-5).
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spelling pubmed-82207152021-06-23 Gliosarcoma vs. glioblastoma: a retrospective case series using molecular profiling Dardis, Christopher Donner, David Sanai, Nader Xiu, Joanne Mittal, Sandeep Michelhaugh, Sharon K. Pandey, Manjari Kesari, Santosh Heimberger, Amy B. Gatalica, Zoran Korn, Michael W. Sumrall, Ashley L. Phuphanich, Surasak BMC Neurol Research BACKGROUND: Gliosarcoma (GS) refers to the presence of mesenchymal differentiation (as seen using light microscopy) in the setting of glioblastoma (GB, an astrocytoma, WHO Grade 4). Although the same approach to treatment is typically adopted for GS and GB, there remains some debate as to whether GS should be considered a discrete pathological entity. Differences between these tumors have not been clearly established at the molecular level. METHODS: Patients with GS (n=48) or GB (n=1229) underwent molecular profiling (MP) with a pan-cancer panel of tests as part of their clinical care. The methods employed included next-generation sequencing (NGS) of DNA and RNA, copy number variation (CNV) of DNA and immunohistochemistry (IHC). The MP comprised 1153 tests in total, although results for each test were not available for every tumor profiled. We analyzed this data retrospectively in order to determine if our results were in keeping with what is known about the pathogenesis of GS by contrast with GB. We also sought novel associations between the MP and GS vs. GB which might improve our understanding of pathogenesis of GS. RESULTS: Potentially meaningful associations (p<0.1, Fisher’s exact test (FET)) were found for 14 of these tests in GS vs. GB. A novel finding was higher levels of proteins mediating immuno-evasion (PD-1, PD-L1) in GS. All of the differences we observed have been associated with epithelial-to-mesenchymal transition (EMT) in other tumor types. Many of the changes we saw in GS are novel in the setting of glial tumors, including copy number amplification in LYL1 and mutations in PTPN11. CONCLUSIONS: GS shows certain characteristics of EMT, by contrast with GB. Treatments targeting immuno-evasion may be of greater therapeutic value in GS relative to GB. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at (10.1186/s12883-021-02233-5). BioMed Central 2021-06-23 /pmc/articles/PMC8220715/ /pubmed/34162346 http://dx.doi.org/10.1186/s12883-021-02233-5 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/, corrected publication 2021 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Dardis, Christopher
Donner, David
Sanai, Nader
Xiu, Joanne
Mittal, Sandeep
Michelhaugh, Sharon K.
Pandey, Manjari
Kesari, Santosh
Heimberger, Amy B.
Gatalica, Zoran
Korn, Michael W.
Sumrall, Ashley L.
Phuphanich, Surasak
Gliosarcoma vs. glioblastoma: a retrospective case series using molecular profiling
title Gliosarcoma vs. glioblastoma: a retrospective case series using molecular profiling
title_full Gliosarcoma vs. glioblastoma: a retrospective case series using molecular profiling
title_fullStr Gliosarcoma vs. glioblastoma: a retrospective case series using molecular profiling
title_full_unstemmed Gliosarcoma vs. glioblastoma: a retrospective case series using molecular profiling
title_short Gliosarcoma vs. glioblastoma: a retrospective case series using molecular profiling
title_sort gliosarcoma vs. glioblastoma: a retrospective case series using molecular profiling
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220715/
https://www.ncbi.nlm.nih.gov/pubmed/34162346
http://dx.doi.org/10.1186/s12883-021-02233-5
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