Methylation and molecular profiles of ependymoma: Influence of patient age and tumor anatomic location

Cho,Hwa Jin; Park,Ha Young; Kim,Kwangsoo; Chae,Heejoon; Paek,Sun Ha; Kim,Seung-Ki; Park,Chul-Kee; Choi,Seung-Hong; Park,Sung-Hye

doi:10.3892/mco.2021.2250

Methylation and molecular profiles of ependymoma: Influence of patient age and tumor anatomic location

Authors:
- Hwa Jin Cho
- Ha Young Park
- Kwangsoo Kim
- Heejoon Chae
- Sun Ha Paek
- Seung-Ki Kim
- Chul-Kee Park
- Seung-Hong Choi
- Sung-Hye Park
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Affiliations: Department of Pathology, Inje University Busan Paik Hospital, Busan 47392, Republic of Korea, Division of Clinical Bioinformatics, Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Republic of Korea, Division of Computer Science, Sookmyung Women's University, Seoul 04310, Republic of Korea, Department of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Republic of Korea, Department of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Republic of Korea, Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
Published online on: March 5, 2021 https://doi.org/10.3892/mco.2021.2250
Article Number: 88

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Abstract

Ependymomas are tumors of the central nervous system that can occur in patients of all ages. Guidelines from the World Health Organization (WHO) for the grading of ependymomas consider patient age, tumor resection range, tumor location and histopathological grade. However, recent studies have suggested that a greater focus on both tumor location and patient age in terms of transcriptomic, genetic, and epigenetic analyses may provide a more accurate assessment of clinical prognosis than the grading system proposed by WHO guidelines. The current study identified the differences and similarities in ependymoma characteristics using three different molecular analyses and methylation arrays. Primary intracranial ependymoma tissues were obtained from 13 Korean patients (9 adults and 4 children), after which whole‑exome sequencing (WES), ion‑proton comprehensive cancer panel (CCP) analysis, RNA sequencing, and Infinium HumanMethylation450 BeadChip array analysis was performed. Somatic mutations, copy number variations, and fusion genes were identified. It was observed that the methylation status and differentially expressed genes were significantly different according to tumor location and patient age. Several novel gene fusions and somatic mutations were identified, including a yes‑associated protein 1 fusion mutation in a child with a good prognosis. Moreover, the methylation microarray revealed that genes associated with neurogenesis and neuron differentiation were hypermethylated in the adult group, whereas genes in the homeobox gene family were hypermethylated in the supratentorial (ST) group. The results confirmed the existence of significantly differentially expressed tumor‑specific genes based on tumor location and patient age. These results provided valuable insight into the epigenetic and genetic profiles of intracranial ependymomas and uncovered potential strategies for the identification of location‑ and age‑based ependymoma‑related prognostic factors.

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