Oligosarcomas, IDH-mutant are distinct and aggressive

Suwala A.K.

Oligosarcomas, IDH-mutant are distinct and aggressive

Issued Date

2022-02-01

Resource Type

Article

ISSN

00016322

eISSN

14320533

DOI

10.1007/s00401-021-02395-z

Scopus ID

2-s2.0-85122093997

Pubmed ID

34967922

Journal Title

Acta Neuropathologica

Volume

143

Issue

2

Start Page

263

End Page

281

Rights Holder(s)

SCOPUS

Bibliographic Citation

Acta Neuropathologica Vol.143 No.2 (2022) , 263-281

Suggested Citation

Suwala A.K. Oligosarcomas, IDH-mutant are distinct and aggressive. Acta Neuropathologica Vol.143 No.2 (2022) , 263-281. 281. doi:10.1007/s00401-021-02395-z Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/86168

Title

Oligosarcomas, IDH-mutant are distinct and aggressive

Author(s)

Suwala A.K.

Other Contributor(s)

Mahidol University

Abstract

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

Keyword(s)

Medicine

URI

https://repository.li.mahidol.ac.th/handle/20.500.14594/86168

Collections

Scopus 2022

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