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

BMC Neurology

Nader Sanai¹  Ashley L. Sumrall²  Manjari Pandey³  Surasak Phuphanich⁴  Christopher Dardis⁵  Zoran Gatalica⁶  Sharon K. Michelhaugh⁷  Sandeep Mittal⁷  Santosh Kesari⁸  Joanne Xiu⁹  Michael W. Korn⁹  David Donner^1,10  Amy B. Heimberger^1,11 

[1] Barrow Brain Tumor Research Center, Department of Neurosurgery, Barrow Neurological Institute;Department of Medical Oncology, Levine Cancer Institute, Atrium Health;Department of Medical Oncology, West Cancer Center, University of Tennessee Health Science Center;Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center;Department of Neurology, Barrow Neurological Institute;Department of Pathology, University of Oklahoma Health Sciences Center;Fralin Biomedical Research Institute, Virginia Tech Carilion School of Medicine;Pacific Neuroscience Institute and Department of Translational Neurosciences and Neurotherapeutics, John Wayne Cancer Institute;Precision Oncology Alliance, Caris Life Sciences;School of Medicine, Creighton University;Simpson Querry Biomedical Research Center, Department of Neurosurgery, Feinberg School of Medicine, Northwestern University;

关键词: Gliosarcoma;    Glioblastoma;    Molecular profiling;    Pan-cancer analysis;    Epithelial-to-mesenchymal transition;    Immuno-evasion;   

DOI  :  10.1186/s12883-021-02233-5

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown