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000157450 1001_ $$aBanan, Rouzbeh$$b0
000157450 245__ $$aInfratentorial IDH-mutant astrocytoma is a distinct subtype.
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000157450 520__ $$aDiffuse 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.
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000157450 7001_ $$aHong, Bujung$$b3
000157450 7001_ $$aLehmann, Ulrich$$b4
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000157450 7001_ $$aBuslei, Rolf$$b8
000157450 7001_ $$aStadelmann, Christine$$b9
000157450 7001_ $$aEhlert, Karoline$$b10
000157450 7001_ $$aPrinz, Marco$$b11
000157450 7001_ $$aAcker, Till$$b12
000157450 7001_ $$aSchittenhelm, Jens$$b13
000157450 7001_ $$aKaul, David$$b14
000157450 7001_ $$0P:(DE-He78)db2e8cf0dd8fa826896839ffee4b1411$$aSchweizer, Leonille$$b15$$udkfz
000157450 7001_ $$0P:(DE-He78)51bf9ae9cb5771b30c483e5597ef606c$$aCapper, David$$b16$$udkfz
000157450 7001_ $$0P:(DE-He78)b15b56a6ed37417d476470c60c0140ff$$aHarter, Patrick$$b17
000157450 7001_ $$aEtminan, Nima$$b18
000157450 7001_ $$0P:(DE-He78)551bb92841f634070997aa168d818492$$aJones, David T W$$b19$$udkfz
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000157450 7001_ $$aHerold-Mende, Christel$$b21
000157450 7001_ $$0P:(DE-He78)92e9783ca7025f36ce14e12cd348d2ee$$aWick, Wolfgang$$b22$$udkfz
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000157450 7001_ $$aHartmann, Christian$$b25
000157450 7001_ $$0P:(DE-He78)d5149ffd74f42a2fa87a086d66645aaa$$aReuß, David$$b26$$eLast author$$udkfz
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