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EPEN-11. TUMOR DIFFERENTIATION IMPACTS THE BIOLOGY OF RECURRENCE IN CHILDHOOD POSTERIOR FOSSA EPENDYMOMA

Donson, Andrew; Ritzmann, Timothy; Willard, Nicholas; Griesinger, Andrea; Amani, Vladimir; Harris, Faith; Grimaldo, Enrique; Sanford, Bridget; Riemondy, Kent; Hankinson, Todd; Grundy, Richard; Foreman, Nicholas

EPEN-11. TUMOR DIFFERENTIATION IMPACTS THE BIOLOGY OF RECURRENCE IN CHILDHOOD POSTERIOR FOSSA EPENDYMOMA Thumbnail


Authors

Andrew Donson

Nicholas Willard

Andrea Griesinger

Vladimir Amani

Faith Harris

Enrique Grimaldo

Bridget Sanford

Kent Riemondy

Todd Hankinson

RICHARD GRUNDY richard.grundy@nottingham.ac.uk
Professor of Paediatric Neuro-Oncology

Nicholas Foreman



Abstract

Ependymoma (EPN) of childhood is curable in only 50% of cases, with recurrences in the remainder that are refractory to treatment. In recent years significant advances have been made in understanding the molecular and cellular biology of EPN. Recent studies show that PFA subgroup EPN are comprised of multiple neoplastic subpopulations that show undifferentiated, differentiated and mesenchymal characteristics. These studies focused on tumor at presentation, with recurrent EPN being less well understood. In the present longitudinal study we examine changes in neoplastic cell heterogeneity in serial presentations of PFA EPN using deconvolution (Cibersort) of bulk RNAseq data. Analysis of a cohort of 48 PFA EPN presenting at Children’s Colorado showed survival and PFA1/PFA2 subtype assignment was associated with the proportion of individual neoplastic subpopulations as determined by deconvolution. Tumors that subsequently regrew had a significantly higher estimated proportion of undifferentiated EPN cells (UEC) at presentation, than those that were non-recurrent after 5 years follow-up. This outcome association potentially age related, as UEC proportions are significantly higher in PFA arising in children < 1 year old who have a particularly poor prognosis. Changes in PFA neoplastic subpopulations at recurrence was performed in two cohorts of patients from Children’s Colorado (n=23) and Nottingham, UK (n=15). As a whole, no subpopulation proportion was significantly changed at recurrence. However, separation of PFA into subtypes PFA1 and PFA2 revealed an increase in the proportion of the cilia-differentiated EPN cell subpopulation is more frequent event in PFA1 (15/24), and rare in PFA2 (2/11). Changes in other neoplastic subpopulations at recurrence were smaller and only seen in PFA1, both UEC and mesenchymal subpopulations being lower at recurrence. In summary, only PFA1 showed dynamic changes in neoplastic subpopulation proportions at recurrence, with potential impacts on transcriptomic based-subgroup assignment, whereas PFA2 proportions remained largely stable.

Journal Article Type Article
Acceptance Date Mar 1, 2021
Online Publication Date Jun 1, 2021
Publication Date 2021-06
Deposit Date Nov 7, 2022
Publicly Available Date Nov 8, 2022
Journal Neuro-Oncology
Print ISSN 1522-8517
Electronic ISSN 1573-7373
Peer Reviewed Not Peer Reviewed
Volume 23
Issue Supplement 1
Pages i15-i16
DOI https://doi.org/10.1093/neuonc/noab090.061
Public URL https://nottingham-repository.worktribe.com/output/13181173
Publisher URL https://academic.oup.com/neuro-oncology/article/23/Supplement_1/i15/6288317

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