Hinz, Felix and Friedel, Dennis and Korshunov, Andrey and Ippen, Franziska M. and Bogumil, Henri and Banan, Rouzbeh and Brandner, Sebastian and Hasselblatt, Martin and Boldt, Henning B. and Dirse, Vaidas and Dohmen, Hildegard and Aronica, Eleonora and Brodhun, Michael and Broekman, Marike L. D. and Capper, David and Cherkezov, Asan and Deng, Maximilian Y. and van Dis, Vera and Felsberg, Joerg and Frank, Stephan and French, Pim J. and Gerlach, Ruediger and Goebel, Kirsten and Goold, Eric and Hench, Juergen and Kantelhardt, Sven and Kohlhof-Meinecke, Patricia and Krieg, Sandro and Mawrin, Christian and Morrison, Gillian and Muehlebner, Angelika and Ozduman, Koray and Pfister, Stefan M. and Poliani, Pietro Luigi and Prinz, Marco and Reifenberger, Guido and Riemenschneider, Markus J. and Sankowski, Roman and Schrimpf, Daniel and Sill, Martin and Snuderl, Matija and Verdijk, Robert M. and Voisin, Mathew R. and Wesseling, Pieter and Wick, Wolfgang and Reuss, David E. and von Deimling, Andreas and Sahm, Felix and Maas, Sybren L. N. and Suwala, Abigail K. (2025) IDH-mutant astrocytomas with primitive neuronal component have a distinct methylation profile and a higher risk of leptomeningeal spread. ACTA NEUROPATHOLOGICA, 149 (1): 12. ISSN 0001-6322, 1432-0533
Full text not available from this repository. (Request a copy)Abstract
IDH-mutant astrocytomas are diffuse gliomas that are defined by characteristic mutations in IDH1 or IDH2 and do not have complete 1p/19q co-deletion. The established grading criteria include histological features of brisk mitotic activity (grade 3) and necrosis and/or microvascular proliferation (grade 4). In addition, homozygous deletion of the CDKN2A/B locus has recently been implemented as a molecular marker for grade 4 IDH-mutant astrocytomas. Here, we describe a subgroup of high-grade IDH-mutant astrocytomas characterised by a primitive neuronal component based on histology and a distinct DNA methylation profile (n = 51, ASTRO PNC). Misinterpretation as carcinoma metastasis was common, since GFAP expression was absent in the primitive neuronal component, whereas TTF-1 expression was detected in 15/19 cases (79%) based on immunohistochemistry. Apart from mutations in IDH1, TP53, and ATRX, we observed enrichment for alterations in RB1 (n = 19/51, 37%) and MYCN (n = 14/51, 27%). Homozygous CDKN2A/B deletion (n = 1/51, 2%) and CDK4 amplification (n = 3/51, 6%) were relatively rare events. Clinical (n = 31 patients) and survival data (n = 23 patients) indicate a clinical behaviour similar to other CNS WHO grade 4 IDH-mutant astrocytomas, however with an increased risk for leptomeningeal (n = 7) and extra-axial (n = 2) spread. Taken together, ASTRO PNC is defined by a distinct molecular and histological appearance that can mimic metastatic disease and typically follows an aggressive clinical course.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CENTRAL-NERVOUS-SYSTEM; CLASSIFICATION; GLIOBLASTOMA; Astrocytoma; IDH-mutant; Primitive neuronal component; DNA methylation; <italic>RB1</italic>; <italic>MYCN</italic> |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Neuropathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 23 Mar 2026 13:36 |
| Last Modified: | 23 Mar 2026 13:36 |
| URI: | https://pred.uni-regensburg.de/id/eprint/68097 |
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