Journal Article

DKFZ-2021-00359

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Ultra high-risk PFA ependymoma is characterized by loss of chromosome 6q.

Baroni, L. ; Sundaresan, L. ; Heled, A. ; Coltin, H. ; Pajtler, K. W.DKFZ* ; Lin, T. ; Merchant, T. E. ; McLendon, R. ; Faria, C. ; Buntine, M. ; White, C. L. ; Pfister, S. M.DKFZ* ; Gilbert, M. R. ; Armstrong, T. S. ; Bouffet, E. ; Kumar, S. ; Taylor, M. D. ; Aldape, K. D. ; Ellison, D. W. ; Gottardo, N. G. ; Kool, M.DKFZ* ; Korshunov, A.DKFZ* ; Hansford, J. R. ; Ramaswamy, V.

2021
Oxford Univ. Press Oxford

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Please use a persistent id in citations: doi:10.1093/neuonc/noab034

Abstract: Within PF-EPN-A, 1q gain is a marker of poor prognosis, however, it is unclear if within PF-EPN-A additional cytogenetic events exist which can refine risk stratification.Five independent non-overlapping cohorts of PF-EPN-A were analyzed applying genome wide methylation arrays for chromosomal and clinical variables predictive of survival.Across all cohorts, 663 PF-EPN-A were identified. The most common broad copy number event was 1q gain (18.9%), followed by 6q loss (8.6%), 9p gain (6.5%), and 22q loss (6.8%). Within 1q gain tumors, there was significant enrichment for 6q loss (17.7%), 10q loss (16.9%) and 16q loss (15.3%). The 5-year progression free survival (PFS) was strikingly worse in those patients with 6q loss, with a 5-year PFS of 50% (95%CI 45-55%) for balanced tumors, compared with 32% (95%CI 24-44%) for 1q gain only, 7.3% (95%CI 2.0-27%) for 6q loss only and 0 for both 1q gain and 6q loss (p=1.65x10 -13 ). After accounting for treatment, 6q loss remained the most significant independent predictor of survival in PF-EPN-A but is not in PF-EPN-B. Distant relapses were more common in 1q gain irrespective of 6q loss. RNA-sequencing comparing 6q loss to 6q balanced PF-EPN-A suggests that 6q loss forms a biologically distinct group.We have identified an ultra high-risk PF-EPN-A ependymoma subgroup, which can be reliably ascertained using cytogenetic markers in routine clinical use. A change in treatment paradigm is urgently needed for this particular subset of PF-EPN-A where novel therapies should be prioritized for upfront therapy.

Keyword(s): 1q gain ; 6qloss ; PFA ; PFB ; ependymoma ; posterior fossa ; subgrouping

Note: 2021 Aug 2;23(8):1360-1370

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Contributing Institute(s):

1. B062 Pädiatrische Neuroonkologie (B062)
2. DKTK HD zentral (HD01)
3. KKE Neuropathologie (B300)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2021

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Database coverage:
; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Essential Science Indicators ; IF >= 10 ; JCR ; Nationallizenz ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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