Infratentorial C11orf95 -fused gliomas share histologic, immunophenotypic, and molecular characteristics of supratentori
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Infratentorial C11orf95‑fused gliomas share histologic, immunophenotypic, and molecular characteristics of supratentorial RELA‑fused ependymoma Camille Keenan1 · Richard T. Graham1 · Julie H. Harreld2 · John T. Lucas Jr.3 · David Finkelstein4 · David Wheeler4 · Xiaoyu Li5 · James Dalton5 · Santhosh A. Upadhyaya1 · Susana C. Raimondi5 · Frederick A. Boop6 · Michael DeCuypere6 · Jinghui Zhang4 · Anna Vinitsky1 · Lu Wang5 · Jason Chiang5,7 Received: 23 August 2020 / Revised: 11 October 2020 / Accepted: 12 October 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Ependymomas are a heterogeneous group of gliomas that occur across CNS compartments and show a wide range of histopathology. DNA methylome profiling and transcriptome analysis have identified at least nine molecular groups of ependymoma separated by anatomical sites and molecular alterations [6]. Supratentorial (ST) ependymomas characteristically harbor gene fusions involving RELA or YAP1 [1, 7]. There are two broad groups of posterior fossa (PF) ependymomas: PFA occurs in young children with worse prognosis, while PFB occurs in older children and adults with better outcomes [2, 5, 8]. While PF ependymomas with C11orf95-RELA fusions have been observed [4], it remains unclear whether they represent a distinct subset of ependymoma or are closely related to ST RELA-fused ependymomas, despite their infratentorial location. We identified three infratentorial (one cervicomedullary and two cerebellar, Fig. 1a–c and Supplementary Table 1, online resource) gliomas with histopathologic features Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00401-020-02238-3) contains supplementary material, which is available to authorized users.
closely resembling ST RELA-fused ependymomas (Fig. 1d–f and Supplementary Figs. 1 and 2, online resource): All tumors had non-infiltrative growth and distinct margins from the adjacent cerebellar or spinal cord tissue. The cytology and architecture varied among and within the same tumors, but a monotonous tumor cell population, cytoplasmic clearing, perivascular anucleate zones, and dystrophic microcalcifications were consistent features. The cervicomedullary tumor additionally showed focal papillary growth. Mitotic activity was readily apparent, and Ki-67 labeling was high in all tumors, justifying a high-grade designation. All tumors showed characteristic immunophenotype of ST RELA-fused ependymomas—there was variable GFAP immunoreactivity. Olig2 and Sox10 were expressed in occasional cells. All tumors were diffusely and strongly positive for L1CAM and retained nuclear immunoreactivity for trimethylation of histone H3 K27 residue. Rearrangements of C11orf95 and RELA were identified by fluorescence in situ hybridization (FISH) in two (cases 2 and 3) and one (case 3) tumor, respectively (Fig. 1g and Supplementary Fig. 3, online resource). By RNA sequencing, we identified C11orf95-MAML2, C11orf95-NCOA2,
* Anna Vinitsky [email protected]
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