Johannes Nowak1,2, Stephanie Theresa Jünger3, Henner Huflage4, Carolin Seidel5, Annika Hohm5, Lindsey A Vandergrift6, Katja von Hoff7, Stefan Rutkowski7, Torsten Pietsch3, Monika Warmuth-Metz5. 1. Reference Center for Neuroradiology, Institute for Diagnostic and Interventional Neuroradiology, University Hospital of Würzburg, Josef-Schneider-Str. 11, 97080, Würzburg, Germany. Nowak_J1@ukw.de. 2. Department of Diagnostic and Interventional Radiology, University Hospital of Würzburg, Oberdürrbacher Str. 6, 97080, Würzburg, Germany. Nowak_J1@ukw.de. 3. Department of Neuropathology, Brain Tumor Reference Center of the DGNN, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany. 4. Department of Diagnostic and Interventional Radiology, University Hospital of Würzburg, Oberdürrbacher Str. 6, 97080, Würzburg, Germany. 5. Reference Center for Neuroradiology, Institute for Diagnostic and Interventional Neuroradiology, University Hospital of Würzburg, Josef-Schneider-Str. 11, 97080, Würzburg, Germany. 6. Departments of Radiology and Pathology, Massachusetts General Hospital, Harvard Medical School, 149 Thirteenth St, MA 02129, Charlestown, USA. 7. Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
Abstract
PURPOSE: Epigenetic profiling has recently identified clinically and molecularly distinct subgroups of ependymoma. The 2016 World Health Organization (WHO) classification recognized supratentorial ependymomas (ST-EPN) with REL-associated protein/p65 (RELA) fusion as a clinicopathological entity. These tumors represent 70% of pediatric ST-EPN characterized by recurrent C11orf95-RELA fusion transcripts, which lead to pathological activation of the nuclear factor 'kappa-light-chain-enhancer' of activated B-cells (NF-κB) signaling pathway. Cyclin-dependent kinase inhibitor 2A (CDKN2A) inactivation has also been reported to correlate with poor prognosis. Here, we systematically describe magnetic resonance imaging (MRI) characteristics of RELA-fused ST-EPN, with respect to CDKN2A deletion status. METHODS: Our cohort of patients with ST-EPN (n = 57) was obtained from the database of the German Brain Tumor Reference Center of the German Society for Neuropathology and Neuroanatomy (DGNN), and tumors were diagnosed according to the 2016 WHO classification. Molecular characterization identified 47 RELA-fused tumors. We analyzed the preoperative MRI according to standardized criteria, and comparison was performed between CDKN2A altered (n = 21) and CDKN2A wild type (n = 26) tumors. RESULTS: The RELA-fused ST-EPN showed a spectrum of predominantly hemispheric tumors with cysts and necrosis. Statistical analysis on CDKN2A status revealed significant differences in terms of younger manifestation age (p =0.002) and more intratumoral hemorrhage in T2-weighted imaging (T2WI) (p =0.010) in wild type tumors; however, the location was not a parameter for differentiation. CONCLUSION: This study first provides comprehensive MRI data for RELA-fused ST-EPN as a distinct entity, with further interest on CDKN2A genomic status. Patient stratification by morphological MRI alone seems difficult at present. The results may support ongoing research in ST-EPN within the framework of the radiogenomics concept.
PURPOSE: Epigenetic profiling has recently identified clinically and molecularly distinct subgroups of ependymoma. The 2016 World Health Organization (WHO) classification recognized supratentorial ependymomas (ST-EPN) with REL-associated protein/p65 (RELA) fusion as a clinicopathological entity. These tumors represent 70% of pediatric ST-EPN characterized by recurrent C11orf95-RELA fusion transcripts, which lead to pathological activation of the nuclear factor 'kappa-light-chain-enhancer' of activated B-cells (NF-κB) signaling pathway. Cyclin-dependent kinase inhibitor 2A (CDKN2A) inactivation has also been reported to correlate with poor prognosis. Here, we systematically describe magnetic resonance imaging (MRI) characteristics of RELA-fused ST-EPN, with respect to CDKN2A deletion status. METHODS: Our cohort of patients with ST-EPN (n = 57) was obtained from the database of the German Brain Tumor Reference Center of the German Society for Neuropathology and Neuroanatomy (DGNN), and tumors were diagnosed according to the 2016 WHO classification. Molecular characterization identified 47 RELA-fused tumors. We analyzed the preoperative MRI according to standardized criteria, and comparison was performed between CDKN2A altered (n = 21) and CDKN2A wild type (n = 26) tumors. RESULTS: The RELA-fused ST-EPN showed a spectrum of predominantly hemispheric tumors with cysts and necrosis. Statistical analysis on CDKN2A status revealed significant differences in terms of younger manifestation age (p =0.002) and more intratumoral hemorrhage in T2-weighted imaging (T2WI) (p =0.010) in wild type tumors; however, the location was not a parameter for differentiation. CONCLUSION: This study first provides comprehensive MRI data for RELA-fused ST-EPN as a distinct entity, with further interest on CDKN2A genomic status. Patient stratification by morphological MRI alone seems difficult at present. The results may support ongoing research in ST-EPN within the framework of the radiogenomics concept.
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