000157450 001__ 157450 000157450 005__ 20240229123138.0 000157450 0247_ $$2doi$$a10.1007/s00401-020-02194-y 000157450 0247_ $$2pmid$$apmid:32776277 000157450 0247_ $$2ISSN$$a0001-6322 000157450 0247_ $$2ISSN$$a1432-0533 000157450 0247_ $$2altmetric$$aaltmetric:88010578 000157450 037__ $$aDKFZ-2020-01629 000157450 041__ $$aeng 000157450 082__ $$a610 000157450 1001_ $$aBanan, Rouzbeh$$b0 000157450 245__ $$aInfratentorial IDH-mutant astrocytoma is a distinct subtype. 000157450 260__ $$aHeidelberg$$bSpringer$$c2020 000157450 3367_ $$2DRIVER$$aarticle 000157450 3367_ $$2DataCite$$aOutput Types/Journal article 000157450 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1608122851_20752 000157450 3367_ $$2BibTeX$$aARTICLE 000157450 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000157450 3367_ $$00$$2EndNote$$aJournal Article 000157450 500__ $$a2020 Oct;140(4):569-581#LA:B300# 000157450 520__ $$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. 000157450 536__ $$0G:(DE-HGF)POF3-312$$a312 - Functional and structural genomics (POF3-312)$$cPOF3-312$$fPOF III$$x0 000157450 588__ $$aDataset connected to CrossRef, PubMed, 000157450 7001_ $$0P:(DE-He78)d20d08adc992abdb6ccffa1686f1ba17$$aStichel, Damian$$b1$$udkfz 000157450 7001_ $$aBleck, Anja$$b2 000157450 7001_ $$aHong, Bujung$$b3 000157450 7001_ $$aLehmann, Ulrich$$b4 000157450 7001_ $$0P:(DE-He78)c77fccff3e6c42b017b2e8a09813590c$$aSuwala, Abigail$$b5$$udkfz 000157450 7001_ $$0P:(DE-He78)856d5c1d0205a79190ed88218ffaf9b2$$aReinhardt, Annekathrin$$b6$$udkfz 000157450 7001_ $$0P:(DE-He78)e54a1e0999c1d8c95869ef9188b794cc$$aSchrimpf, Daniel$$b7$$udkfz 000157450 7001_ $$aBuslei, Rolf$$b8 000157450 7001_ $$aStadelmann, Christine$$b9 000157450 7001_ $$aEhlert, Karoline$$b10 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