PXD030442-1

PXD030442 is an original dataset announced via ProteomeXchange.

Title	Oligosarcomas, IDH-mutant are distinct and aggressive
Description	Oligodendrogliomas are defined by IDH-mutations and codeletions 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 23 IDH-mutant oligosarcomas forming a distinct methylation class. The tumors were recurrences from prior oligodendrogliomas or developed de novo. Precursor tumors of 11 oligosarcomas were histologically and molecularly indistinguishable from conventional oligodendrogliomas. Oligosarcoma tumor cells were embedded in a dens network of reticulin fibers, frequently showing p53 accumulation, positivity for SMA, 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. Oligosarcomas harbored an increased chromosomal copy number variation load with frequent CDKN2A/B deletions. Proteomic profiling demonstrated oligosarcomas to be highly distinct from conventional 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 than for grade 3 oligodendrogliomas and comparable to that of grade 4 IDH-mutant astrocytomas. These results establish oligosarcoma as a distinct type of IDH-mutant glioma differing from conventional oligodendrogliomas on the histologic, epigenetic, proteomic, molecular and clinical level. Diagnosis can be based on the characteristic DNA methylation profile or the combined evidence of sarcomatous histology, IDH-mutation and an oligodendroglioma-typical molecular alteration as TERT promoter mutation and/or 1p/19q codeletion.
HostingRepository	MassIVE
AnnounceDate	2021-12-28
AnnouncementXML	Submission_2021-12-28_01:12:49.665.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Dennis Friedel
SpeciesList	scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2021-12-16 04:52:07	ID requested
⏵ 1	2021-12-28 01:12:50	announced

no publication

submitter keyword: Oligosarcoma, Oligodendroglioma

David E.Reuss
contact affiliation	University Hospital Heidelberg Neuropathology
contact email	David.Reuss@med.uni-heidelberg.de
lab head
Dennis Friedel
contact affiliation	University Hospital Heidelberg
contact email	Dennis.Friedel@med.uni-heidelberg.de
dataset submitter

MassIVE dataset URI

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