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

Christopher Dardis*, David Donner, Nader Sanai, Joanne Xiu, Sandeep Mittal, Sharon K. Michelhaugh, Manjari Pandey, Santosh Kesari, Amy B. Heimberger, Zoran Gatalica, Michael W. Korn, Ashley L. Sumrall, Surasak Phuphanich

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number231
JournalBMC Neurology
Volume21
Issue number1
DOIs
StatePublished - Dec 2021

Keywords

  • Epithelial-to-mesenchymal transition
  • Glioblastoma
  • Gliosarcoma
  • Immuno-evasion
  • Molecular profiling
  • Pan-cancer analysis

ASJC Scopus subject areas

  • Clinical Neurology

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