Title :

Oligosarcomas, idh-mutant are distinct and aggressive

Author(s) :

Suwala, Abigail K. [Auteur]
Felix, Marius [Auteur]
Universität Heidelberg [Heidelberg] = Heidelberg University
Friedel, Dennis [Auteur]
Stichel, Damian [Auteur]
Schrimpf, Daniel [Auteur]
Hinz, Felix [Auteur]
Hewer, Ekkehard [Auteur]
Schweizer, Leonille [Auteur]
Dohmen, Hildegard [Auteur]
Pohl, Ute [Auteur]
Staszewski, Ori [Auteur]
University Hospital Freiburg
Korshunov, Andrey [Auteur]
Heidelberg University Hospital [Heidelberg]
Stein, Marco [Auteur]
Wongsurawat, Thidathip [Auteur]
Cheunsuacchon, Pornsuk [Auteur]
Sathornsumetee, Sith [Auteur]
Koelsche, Christian [Auteur]
NN Burdenko Neurosurgical Institute [NNBNI]
Turner, Clinton [Auteur]
Le Rhun, Emilie [Auteur]
Universität Zürich [Zürich] = University of Zurich [UZH]
Muhlebner, Angelika [Auteur]
Schucht, Philippe [Auteur]
Bern University Hospital [Berne] [Inselspital]
Ozduman, Koray [Auteur]
Ono, Takahiro [Auteur]
Shimizu, Hiroaki [Auteur]
Prinz, Marco [Auteur]
Acker, Till [Auteur]
Herold-Mende, Christel [Auteur]
Kessler, Tobias [Auteur]
Wick, Wolfgang [Auteur]
Capper, David [Auteur]
Wesseling, Pieter [Auteur]
Sahm, Felix [Auteur]
Von Deimling, Andreas [Auteur]
Hartmann, Christian [Auteur]
Reuss, David E. [Auteur]

Journal title :

Acta Neuropathologica

Abbreviated title :

Acta Neuropathol.

Volume number :

143

Pages :

263-281

Publication date :

2021-12-30

ISSN :

0001-6322

Keyword(s) :

Subtype
Codeletion
19q
1p
Gliosarcoma
Oligodendroglioma
Oligosarcoma
YAP1
NF1
TP53
TERT
DNA methylation
Type
SMA
Variant
Prognosis

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

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 ...
Show more >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.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

INSERM
Université de Lille

Collections :

• Autres travaux scientifiques

Submission date :

2022-06-15T14:00:42Z
2023-03-08T10:33:06Z