Significant increase of high-risk chromosome 1q gain and 6q loss at recurrence in posterior fossa group A ependymoma: A multicenter study

• DOI: 10.1093/neuonc/noad096
• Publication Date: 2023-05-26T01:44:23Z
• Authors: Andrew M Donson; Kelsey C Bertrand; Kent A Riemondy; Dexiang Gao; Yonghua Zhuang; Bridget Sanford; Gregory A Norris; Rebecca J Chapman; Rui Fu; Nicholas Willard; Andrea M Griesinger; Graziella Ribeiro...; Vladimir Amani; Enrique Grimaldo; Todd C Hankinson; Ffyona Booker; Martin Sill; Richard G Grundy; Kristian W Pajtler; David W Ellison; Nicholas K Foreman; Timothy A Ritzmann
• Keywords: Ependymoma; Chromosome instability

Abstract Background Ependymoma (EPN) posterior fossa group A (PFA) has the highest rate of recurrence and worst prognosis all EPN molecular groups. At relapse, it is typically incurable even with re-resection re-irradiation. The biology recurrent PFA remains largely unknown; however, increasing use surgery at first now provided access to clinical samples facilitate a better understanding this. Methods In this large longitudinal international multicenter study, we examined matched primary disease from patients investigate recurrence. Results DNA methylome derived copy number variants (CNVs) revealed large-scale chromosome gains losses in PFA. CNV changes were dominated by 1q gain and/or 6q loss, both previously identified as high-risk factors PFA, which present 23% presentation but increased 61% Multivariate survival analyses cohort showed that cases or loss significantly more likely recur again. Predisposition 1q+/6q− correlated hypomethylation heterochromatin-associated presentation. Cellular had higher proportions proliferative neuroepithelial undifferentiated progenitors decreased differentiated neoplastic subpopulations. Conclusions This study provides clinically preclinically actionable insights into predisposition signature potential risk-classifier for trial stratification. We show cellular heterogeneity PFAs evolves because genetic evolution cells.