Journal Article

DKFZ-2020-02381

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png A subset of pediatric-type thalamic gliomas share a distinct DNA methylation profile, H3K27me3 loss and frequent alteration of EGFR.

Sievers, P. (First author)DKFZ* ; Sill, M.DKFZ* ; Schrimpf, D.DKFZ* ; Stichel, D.DKFZ* ; Reuß, D.DKFZ* ; Sturm, D.DKFZ* ; Hench, J. ; Frank, S. ; Krskova, L. ; Vicha, A. ; Zapotocky, M. ; Bison, B. ; Castel, D. ; Grill, J. ; Debily, M.-A.DKFZ* ; Harter, P. N.DKFZ* ; Snuderl, M. ; Kramm, C. M. ; Reifenberger, G.DKFZ* ; Korshunov, A.DKFZ* ; Jabado, N. ; Wesseling, P. ; Wick, W.DKFZ* ; Solomon, D. A. ; Perry, A. ; Jacques, T. S. ; Jones, C. ; Witt, O.DKFZ* ; Pfister, S.DKFZ* ; von Deimling, A.DKFZ* ; Jones, D. (Last author)DKFZ* ; Sahm, F. (Last author)DKFZ*

2021
Oxford Univ. Press Oxford

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Please use a persistent id in citations: doi:10.1093/neuonc/noaa251

Abstract: Malignant astrocytic gliomas in children show a remarkable biological and clinical diversity. Small in-frame insertions or missense mutations in the EGFR gene have recently been identified in a distinct subset of pediatric-type bithalamic gliomas with a unique DNA methylation pattern.Here, we investigated an epigenetically homogeneous cohort of malignant gliomas (n=58) distinct from other subtypes and enriched for pediatric cases and thalamic location, in comparison with this recently identified subtype of pediatric bithalamic gliomas.EGFR gene amplification was detected in 16/58 (27%) tumors, and missense mutations or small in-frame insertions in EGFR were found in 20/30 tumors with available sequencing data (67%; five of them co-occurring with EGFR amplification). Additionally, eight of the 30 tumors (27%) harbored an H3.1 or H3.3 K27M mutation (six of them with a concomitant EGFR alteration). All tumors tested showed loss of H3K27me3 staining, with evidence of EZHIP overexpression in the H3 wildtype cases. Although some tumors indeed showed a bithalamic growth pattern, a significant proportion of tumors occurred in the unilateral thalamus or in other (predominantly midline) locations.Our findings present a distinct molecular class of pediatric-type malignant gliomas largely overlapping with the recently reported bithalamic gliomas characterized by EGFR alteration, but additionally showing a broader spectrum of EGFR alterations and tumor localization. Global H3K27me3 loss in this group appears to be mediated by either H3 K27 mutation or EZHIP overexpression. EGFR inhibition may represent a potential therapeutic strategy in these highly aggressive gliomas.

Note: 2021 Jan 30;23(1):34-43 #EA:B360#LA:B300#

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Contributing Institute(s):

1. DKTK HD zentral (HD01)
2. DKTK ED ES zentral (ED01)
3. KKE Neuropathologie (B300)
4. B062 Pädiatrische Neuroonkologie (B062)
5. KKE Neuroonkologie (B320)
6. Pediatric Glioma (B360)

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 ; NCBI Molecular Biology Database ; Nationallizenz ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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