Journal Article

DKFZ-2020-01629

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Infratentorial IDH-mutant astrocytoma is a distinct subtype.

Banan, R. ; Stichel, D.DKFZ* ; Bleck, A. ; Hong, B. ; Lehmann, U. ; Suwala, A.DKFZ* ; Reinhardt, A.DKFZ* ; Schrimpf, D.DKFZ* ; Buslei, R. ; Stadelmann, C. ; Ehlert, K. ; Prinz, M. ; Acker, T. ; Schittenhelm, J. ; Kaul, D. ; Schweizer, L.DKFZ* ; Capper, D.DKFZ* ; Harter, P.DKFZ* ; Etminan, N. ; Jones, D. T. W.DKFZ* ; Pfister, S. M.DKFZ* ; Herold-Mende, C. ; Wick, W.DKFZ* ; Sahm, F.DKFZ* ; von Deimling, A.DKFZ* ; Hartmann, C. ; Reuß, D. (Last author)DKFZ*

2020
Springer Heidelberg

This record in other databases:  

Please use a persistent id in citations: doi:10.1007/s00401-020-02194-y

Abstract: Diffuse IDH-mutant astrocytic tumors are rarely diagnosed in the cerebellum or brainstem. In this multi-institutional study, we characterized a series of primary infratentorial IDH-mutant astrocytic tumors with respect to clinical and molecular parameters. We report that about 80% of IDH mutations in these tumors are of non-IDH1-R132H variants which are rare in supratentorial astrocytomas. Most frequently, IDH1-R132C/G and IDH2-R172S/G mutations were present. Moreover, the frequencies of ATRX-loss and MGMT promoter methylation, which are typically associated with IDH mutations in supratentorial astrocytic tumors, were significantly lower in the infratentorial compartment. Gene panel sequencing revealed two samples with IDH1-R132C/H3F3A-K27M co-mutations. Genome-wide DNA methylation as well as chromosomal copy number profiling provided further evidence for a molecular distinctiveness of infratentorial IDH-mutant astrocytomas. Clinical outcome of patients with infratentorial IDH-mutant astrocytomas is significantly better than that of patients with diffuse midline gliomas, H3K27M-mutant (p < 0.005) and significantly worse than that of patients with supratentorial IDH-mutant astrocytomas (p = 0.028). The presented data highlight the very existence and distinctiveness of infratentorial IDH-mutant astrocytomas that have important implications for diagnostics and prognostication. They imply that molecular testing is critical for detection of these tumors, since many of these tumors cannot be identified by immunohistochemistry applied for the mutated IDH1-R132H protein or loss of ATRX.

Note: 2020 Oct;140(4):569-581#LA:B300#

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Contributing Institute(s):

1. KKE Neuropathologie (B300)
2. DKTK HD zentral (HD01)
3. DKTK BE zentral (BE01)
4. DKTK FM zentral (FM01)
5. Pediatric Glioma (B360)
6. B062 Pädiatrische Neuroonkologie (B062)
7. KKE Neuroonkologie (B320)

Research Program(s):

1. 312 - Functional and structural genomics (POF3-312) (POF3-312)

Appears in the scientific report 2020

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Springer ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 15 ; JCR ; NCBI Molecular Biology Database ; Nationallizenz ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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