Ependymomas in infancy: underlying genetic alterations, histological features, and clinical outcome
Open Access
- 30 May 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Child's Nervous System
- Vol. 36 (11), 2693-2700
- https://doi.org/10.1007/s00381-020-04655-x
Abstract
Introduction Young age is an adverse prognostic factor in children with ependymomas. Treatment of these infants is challenging since beneficial therapeutic options are limited. As ependymomas are considered a biologically heterogeneous group, we aimed to characterize infant ependymomas with regard to their histological and genetic features. Materials and methods We analyzed 28 ependymomas occurring in children younger than 18 months at diagnosis enrolled into the HIT2000-E protocols with the aim to postpone irradiation until the age of 18 months if possible. All cases underwent neuropathological review, including immunohistochemical characterization. Genome-wide copy number alterations (CNA) were assessed by molecular inversion probe assays, and RELA and YAP1 fusions were detected by RT-PCR and sequencing. Results All infant ependymomas were anaplastic (WHO grade III). Twenty-one (75%) cases were located in the posterior fossa. Gross total resection was accomplished in 12 (57%) of these cases. All posterior fossa tumors showed loss of H3-K27me3 characteristic of PFA ependymomas. CNA analysis showed a stable genome in all cases with lack of chromosome 1q gain, an adverse prognostic marker in PFA ependymomas of older children. However, after a median follow-up of 5.4 years, 15 (71%) relapsed, and 9 (43%) died. Seven ependymomas (25%) occurred in the supratentorial region. Gross total resection could be achieved in only two of these cases. Four tumors carried C11orf95-RELA fusions, and two cases had typical YAP1-MAMLD1 fusions (one case was not analyzable). The RELA-fused cases did not display CDKN2A loss as an adverse indicator of prognosis in this disease entity. Although three infants (43%) with supratentorial ependymomas relapsed, all patients survived (median follow-up, 8.0 years). Conclusion Infant ependymomas seem to fall into three biological entities, with supratentorial tumors carrying RELA or YAP fusions and PFA posterior fossa ependymomas. The latter showed a poor outcome even though chromosome 1q gain was absent.Funding Information
- Deutsche Kinderkrebsstiftung (DKS 2006.03, 2009.19, 2011.01 and 2014.17)
This publication has 29 references indexed in Scilit:
- Supratentorial ependymomas of childhood carry C11orf95–RELA fusions leading to pathological activation of the NF-κB signaling pathwayActa Neuropathologica, 2014
- Molecular inversion probes: a novel microarray technology and its application in cancer researchCancer Genetics, 2012
- Copy Number Gain of 1q25 Predicts Poor Progression-Free Survival for Pediatric Intracranial Ependymomas and Enables Patient Risk Stratification: A Prospective European Clinical Trial Cohort Analysis on Behalf of the Children's Cancer Leukaemia Group (CCLG), Société Française d'Oncologie Pédiatrique (SFOP), and International Society for Pediatric Oncology (SIOP)Clinical Cancer Research, 2012
- Histopathological grading of pediatric ependymoma: reproducibility and clinical relevance in European trial cohortsJournal of Negative Results in BioMedicine, 2011
- Molecular Staging of Intracranial Ependymoma in Children and AdultsJournal of Clinical Oncology, 2010
- Pediatric Ependymoma: Biological PerspectivesMolecular Cancer Research, 2009
- The prognostic value of histological grading of posterior fossa ependymomas in children: a Children's Oncology Group study and a review of prognostic factorsLaboratory Investigation, 2008
- The 2007 WHO classification of tumours of the central nervous systemActa Neuropathologica, 2007
- Radial glia cells are candidate stem cells of ependymomaCancer Cell, 2005
- Genomic Imbalances in Pediatric Intracranial Ependymomas Define Clinically Relevant GroupsThe American Journal of Pathology, 2002