Isomorphic diffuse glioma is a morphologically and molecularly distinct tumour entity with recurrent gene fusions of MYBL1 or MYB and a benign disease course.

Wefers, Annika K and Stichel, Damian and Schrimpf, Daniel and Coras, Roland and Pages, Mélanie and Tauziède-Espariat, Arnault and Varlet, Pascale and Schwarz, Daniel and Söylemezoglu, Figen and Pohl, Ute and Pimentel, José and Meyer, Jochen and Hewer, Ekkehard and Japp, Anna and Joshi, Abhijit and Reuss, David E and Reinhardt, Annekathrin and Sievers, Philipp and Casalini, M Belén and Ebrahimi, Azadeh and Huang, Kristin and Koelsche, Christian and Low, Hu Liang and Rebelo, Olinda and Marnoto, Dina and Becker, Albert J and Staszewski, Ori and Mittelbronn, Michel and Hasselblatt, Martin and Schittenhelm, Jens and Cheesman, Edmund and de Oliveira, Ricardo Santos and Queiroz, Rosane Gomes P and Valera, Elvis Terci and Hans, Volkmar H and Korshunov, Andrey and Olar, Adriana and Ligon, Keith L and Pfister, Stefan M and Jaunmuktane, Zane and Brandner, Sebastian and Tatevossian, Ruth G and Ellison, David W and Jacques, Thomas S and Honavar, Mrinalini and Aronica, Eleonora and Thom, Maria and Sahm, Felix and von Deimling, Andreas and Jones, David T W and Blumcke, Ingmar and Capper, David (2019) Isomorphic diffuse glioma is a morphologically and molecularly distinct tumour entity with recurrent gene fusions of MYBL1 or MYB and a benign disease course. Acta neuropathologica. ISSN 1432-0533. This article is available to all UHB staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their UHB Athens login IDs

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Official URL: https://link.springer.com/article/10.1007%2Fs00401...

Abstract

The "isomorphic subtype of diffuse astrocytoma" was identified histologically in 2004 as a supratentorial, highly differentiated glioma with low cellularity, low proliferation and focal diffuse brain infiltration. Patients typically had seizures since childhood and all were operated on as adults. To define the position of these lesions among brain tumours, we histologically, molecularly and clinically analysed 26 histologically prototypical isomorphic diffuse gliomas. Immunohistochemically, they were GFAP-positive, MAP2-, OLIG2- and CD34-negative, nuclear ATRX-expression was retained and proliferation was low. All 24 cases sequenced were IDH-wildtype. In cluster analyses of DNA methylation data, isomorphic diffuse gliomas formed a group clearly distinct from other glial/glio-neuronal brain tumours and normal hemispheric tissue, most closely related to paediatric MYB/MYBL1-altered diffuse astrocytomas and angiocentric gliomas. Half of the isomorphic diffuse gliomas had copy number alterations of MYBL1 or MYB (13/25, 52%). Gene fusions of MYBL1 or MYB with various gene partners were identified in 11/22 (50%) and were associated with an increased RNA-expression of the respective MYB-family gene. Integrating copy number alterations and available RNA sequencing data, 20/26 (77%) of isomorphic diffuse gliomas demonstrated MYBL1 (54%) or MYB (23%) alterations. Clinically, 89% of patients were seizure-free after surgery and all had a good outcome. In summary, we here define a distinct benign tumour class belonging to the family of MYB/MYBL1-altered gliomas. Isomorphic diffuse glioma occurs both in children and adults, has a concise morphology, frequent MYBL1 and MYB alterations and a specific DNA methylation profile. As an exclusively histological diagnosis may be very challenging and as paediatric MYB/MYBL1-altered diffuse astrocytomas may have the same gene fusions, we consider DNA methylation profiling very helpful for their identification.

Item Type: Article
Additional Information: This article is available to all UHB staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their UHB Athens login IDs
Subjects: QZ Pathology. Oncology
Divisions: Clinical Support > Pathology
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Depositing User: Mr Philip O'Reilly
Date Deposited: 07 Oct 2019 13:15
Last Modified: 07 Oct 2019 13:15
URI: http://www.repository.uhblibrary.co.uk/id/eprint/2453

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