Molecular Characteristics of a ZFTA::RELA Fusion Gliosarcoma: A Case Report

Abstract

The combination of ependymoma and gliosarcoma elements in the same tumor is extremely rare, and the molecular characteristics of these entities are not clear. Here, we present a rare aggressive brain tumor in a 12-year-old boy harboring a ZFTA::RELA gene fusion, a characteristic feature of supratentorial ependymomas. On the other hand, the histopathological, molecular, and methylation profiles were compatible with a diagnosis of a mesenchymal type, IDH wild-type glioblastoma multiforme (GBM). Additional somatic alterations provide evidence of RAS/MAPK signaling pathway activation. Overall, this report highlights the histopathological and molecular characteristics of a rare and aggressive glial tumor.

Keywords

Gliosarcoma ependymosarcoma

Get full access to this article

View all access options for this article.

References

Louis

Perry

Wesseling

, et al. The 2021 WHO classification of tumors of the central nervous system: a summary. Neuro Oncol. 2021;23(8):1231–1251.

Kozak

Mahadevan

Moody

. Adult gliosarcoma: epidemiology, natural history, and factors associated with outcome. Neuro Oncol. 2009;11(2):183–191.

Brennan

Verhaak

RGW

McKenna

, et al. The somatic genomic landscape of glioblastoma. Cell. 2013;155(2):462–477.

Zaki

Mashouf

Woodward

, et al. Genomic landscape of gliosarcoma: distinguishing features and targetable alterations. Sci Rep. 2021;11(1):18009.

Lowder

Hauenstein

Woods

, et al. Gliosarcoma: distinct molecular pathways and genomic alterations identified by DNA copy number/SNP microarray analysis. J Neurooncol. 2019;143(3):381–392.

Mahajan

Nambirajan

Sharma

, et al. Ependymosarcoma harboring C11orf95:RELA fusion transcript: report of two cases and review of the literature. Neuropathology. 2021;41(5):412–421.

Rodriguez

Scheithauer

Perry

, et al. Ependymal tumors with sarcomatous change (“ependymosarcoma”): a clinicopathologic and molecular cytogenetic study. Am J Surg Pathol. 2008;32(5):699–709.

Dadario

Pruitt

Silverstein

, et al. Sarcomatous change of cerebellopontine angle ependymoma following radiosurgery: a case report. Cureus. 2022;14(1):e20864.

Cachia

Wani

Penas-Prado

, et al. C11orf95-RELA fusion present in a primary supratentorial ependymoma and recurrent sarcoma. Brain Tumor Pathol. 2015;32(2):105–111.

10.

Yajima

Takayanagi

Takami

, et al. Novel case of ependymoma-like tumor with mesenchymal differentiation harboring ZFTA::RELA fusion in an adult. Brain Tumor Pathol. 2024;41(3):139–144.

11.

Zehir

Benayed

Shah

, et al. Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients. Nat Med. 2017;23(6):703–713.

12.

Lee

Wang

, et al. Spatiotemporal genomic architecture informs precision oncology in glioblastoma. Nat Genet. 2017;49(4):594–599.

13.

Milinkovic

Skender Gazibara

Manojlovic Gacic

Gazibara

Tanic

. The impact of TP53 and RAS mutations on cerebellar glioblastomas. Exp Mol Pathol. 2014;97(2):202–207.

14.

Fadhlullah

SFB

Halim

NBA

Yeo

JYT

, et al. Pathogenic mutations in neurofibromin identifies a leucine-rich domain regulating glioma cell invasiveness. Oncogene. 2019;38(27):5367–5380.

15.

Philpott

Tovell

Frayling

Cooper

Upadhyaya

. The NF1 somatic mutational landscape in sporadic human cancers. Hum Genomics. 2017;11(1):13.

16.

Verhaak

RGW

Hoadley

Purdom

, et al. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell. 2010;17(1):98–110.