EPEN-07. A MULTICENTER STUDY OF POOR PROGNOSIS CHROMOSOME 1Q GAIN AND/OR 6Q LOSS IN POSTERIOR FOSSA A EPENDYMOMA SHOWS INCREASED PREVALENCE FROM 20% AT DIAGNOSIS TO 60% AT FIRST RECURRENCE

Abstract Ependymoma (EPN) posterior fossa group A (PFA) has the highest rate of recurrence and worst prognosis all EPN types. At relapse, it is typically incurable even with re-resection re-irradiation. The biology recurrent PFA remains largely unknown, which hinders clinical advances. In this longitudinal large multicenter study, we examined matched samples primary disease from patients (n=95) to investigate recurrence. DNA methylomic data was used measure copy number variants (CNVs), revealing progressive scale chromosome gains losses in successive recurrences. These CNV changes were dominated by 1q gain and/or 6q loss (1q+/6q-), both previously identified as high-risk factors EPN, present ~20% at presentation but increased ~60% 1st Because testing not routinely performed, very high incidence been reported. Evolution chromosomal aberrations further explored using analysis single-nuclei RNAseq on approximately 46,000 cells 6 pairs relapse tumors that harbored No evidence rare subclones observed, suggesting rearrangement events occur after initial presentation. Cellular molecular characteristics associated CNVs RNAseq, bulk transcriptomic immunohistochemistry, 1q+/6q- have a significantly higher mitotic index, proportions proliferative epithelial progenitors decreased differentiated neoplastic subpopulations. Multivariate survival analyses showed cases or more likely recur than no change. prevalence shortened survival, suggest these abnormalities should be tested for, for trial stratification.