Oligosarcomas, IDH-mutant are distinct and aggressive

• DOI: 10.1007/s00401-021-02395-z
• Publication Date: 2021-12-30T16:04:23Z
• Authors: Abigail K. Suwala; Marius Felix; Dennis Friedel; Damian Stichel; Daniel Schrimpf; Felix Hinz; Ekkehard Hewer; Leonille Schweizer; Hildegard Dohmen; Ute Pohl; Ori Staszewski; Andrey Korshunov; Marco Stein; Thidathip Wongsur...; Pornsuk Cheunsuac...; Sith Sathornsumetee; Christian Koelsche; Clinton Turner; Emilie Le Rhun; Angelika Mühlebner; Philippe Schucht; Koray Özduman; Takahiro Ono; Hiroaki Shimizu; Marco Prinz; Till Acker; Christel Herold-M...; Tobias Kessler; Wolfgang Wick; David Capper; Pieter Wesseling; Felix Sahm; Andreas von Deimling; Christian Hartmann; David E. Reuss
• Keywords: Oligodendroglial Tumor

Abstract Oligodendrogliomas are defined at the molecular level by presence of an IDH mutation and codeletion chromosomal arms 1p 19q. In past, case reports small studies described gliomas with sarcomatous features arising from oligodendrogliomas, so called oligosarcomas. Here, we report a series 24 IDH-mutant oligosarcomas 23 patients forming distinct methylation class. The tumors were recurrences prior oligodendrogliomas or developed de novo. Precursor 12 histologically molecularly indistinguishable conventional oligodendrogliomas. Oligosarcoma tumor cells embedded in dense network reticulin fibers, frequently showing p53 accumulation, positivity for SMA CALD1, loss OLIG2 gain H3K27 trimethylation (H3K27me3) as compared to primary lesions. 5 no 1p/19q was detectable, although it present Copy number neutral LOH determined underlying mechanism. Oligosarcomas harbored increased copy variation load frequent CDKN2A/B deletions. Proteomic profiling demonstrated be highly CNS WHO grade 3 consistent evidence smooth muscle differentiation. Expression several suppressors reduced NF1 being lost frequently. contrast, oncogenic YAP1 aberrantly overexpressed Panel sequencing revealed mutations TP53 along IDH1/2 TERT promoter mutations. Survival significantly poorer first recurrence than recurrence. These results establish group differing on histologic, epigenetic, proteomic, clinical level. diagnosis can based combined (a) histology, (b) IDH-mutation (c) and/or codeletion, or, unresolved cases, its characteristic DNA profile.