Spinal cord astroblastoma with EWSR1-BEND2 fusion classified as HGNET-MN1 by methylation classification: a case report

Abstract

The most recurrent fusion of central nervous system high-grade neuroepithelial tumor with MN1 alteration (HGNET-MN1) is MN1 rearrangement. Here, we report the case of a 36-year-old man with spinal cord astroblastoma showing Ewing Sarcoma breakpoint region 1/EWS RNA-binding protein 1 (EWSR1)-BEN domain-containing 2 (BEND2) fusion. The patient presented with back pain, gait disturbance and dysesthesia in the lower extremities and trunk. Magnetic resonance imaging showed an intramedullary tumor at the T3-5 level, displaying homogeneous gadolinium enhancement. Partial tumor removal was performed with laminectomy. Histological examinations demonstrated solid growth of epithelioid tumor cells showing high cellularity, a pseudopapillary structure, intervening hyalinized fibrous stroma, and some mitoses. Astroblastoma was diagnosed, classified as HGNET-MN1 by the German Cancer Research Center methylation classifier. MN1 alteration was not detected by fluorescence in situ hybridization (FISH), but EWSR1-BEND2 fusion was detected by FISH and RNA sequencing. Previously, a child with EWSR1-BEND2 fusion-positive spinal astroblastoma classified as HGNET-MN1was reported. In conjunction with that, the present case provides evidence that EWSR1-BEND2 fusion is identified in the entity of HGNET-MN1. Taken together, the BEND2 A Self-archived copy in Kyoto University Research Information Repository https://repository.kulib.kyoto-u.ac.jp 5 alteration rather than MN1 may determine the biology of a subset of the central nervous system HGNET-MN1 subclass. Keywords astroblastoma, CNS high-grade neuroepithelial tumor with MN1 alteration (HGNET-MN1), Ewing Sarcoma breakpoint region 1/EWS RNA-binding protein 1 (EWSR1), BEN domain-containing 2 (BEND2), EWSR1-BEND2 fusion

Soft‐tissue sarcoma with MN1‐BEND2 fusion: A case report and comparison with astroblastoma

“…3 MN1-BEND2 fusion, like MN1 fusions with other partners that have been reported thus far [7][8][9] maintains sequences encoding polyQ stretches, and similar enhancer hijacking mechanisms may be operating. Conversely, a small number of astroblastoma cases with alternative EWSR1-BEND2 fusions have been reported mainly in the spinal cord or brain stem, which belong to the MN1-altered astroblastoma methylation class, [14][15][16] suggesting a more critical role for BEND2 in oncogenesis. BEND2 (Xp22.13) encodes one of nine BEN-domain-containing proteins in humans, and includes two tandem BEN domains in the C-terminus.…”

The Diagnostic and Prognostic Value of BEN-Domain (BEND) Family Genes in Gastric Cancer

“…Correlation analysis of BEND family gene expression with Stemness index, tumor microenvironment in STAD. (1)(2)(3)(4)(5)(6)(7)(8)(9) Correlation analysis between BEND family gene expression and RNAss; (10)(11)(12)(13)(14)(15)(16)(17)(18) Correlation analysis between BEND family gene expression and DNAss; (19)(20)(21)(22)(23)(24)(25)(26)(27) Correlation analysis between BEND family gene expression and stromal score; (28)(29)(30)(31)(32)(33)(34)(35)(36) Correlation analysis between BEND family gene expression and immune score; (37)(38)(39)(40)(41)(42)(43)(44)(45) Correlation analysis between BEND family gene expression and ESTIMATE score. Light brown background indicates that the gene is signi cantly related to the corresponding index (P<0.05).…”

“…The protein synthesized by BEND5 can induce embryonic stem cells to differentiate into primordial germ progenitor-like cells 9 . According to 2 case reports, fusion mutations of BEND2 and some genes may induce the occurrence of spinal astroblastoma and high-grade neuroepithelial tumor 10,11 .BEND6 is an independent factor of neural BEN that binds to mammalian CSL protein CBF1 and antagonizes Notchdependent target activation, and its reduction increases the self-renewal of NSC in the wild-type neocortex 12 . At present, there are few studies on BEND family genes in gastric cancer.…”

Paediatric astroblastoma‐like neuroepithelial tumour of the spinal cord with a MAMLD1‐BEND2 rearrangement

“…25 months from surgery [7][8][9]11]. Only one patient was alive with stable disease at 4.5 years from the diagnosis, after experiencing a tumour relapse at 3.5 years, which was partially resected and treated with proton therapy [10].…”

“…A group of AB-like tumours without MN1 alteration but carrying a EWSR1-BEND2 fusion has recently emerged, with eight cases described with clinical correlates up to date [7][8][9][10][11]. This group is strikingly enriched for non-hemispheric cases, involving either the brainstem (one case) [11], the cervicomedullary junction (three cases) [7,9,10] or the spinal cord (two cases) [8,11]. Half of the cases were paediatric, including an infantile case [7,10,11], and half affected adults in their third or fourth decade [8,9,11].…”