Giant cell glioblastoma does not represent a distinct entity but stratifies into different genetically defined entities

A Wiedey; E Doerner; A zur Mühlen; C Kramm; A Waha; T Pietsch

doi:10.1055/s-0039-1687127

Klinische Pädiatrie, Table of Contents

Klin Padiatr 2019; 231(03): 158
DOI: 10.1055/s-0039-1687127

Abstracts

Georg Thieme Verlag KG Stuttgart · New York

Giant cell glioblastoma does not represent a distinct entity but stratifies into different genetically defined entities

Authors

A Wiedey

¹Institute of Neuropathology, University of Bonn, Germany
E Doerner

¹Institute of Neuropathology, University of Bonn, Germany
A zur Mühlen

¹Institute of Neuropathology, University of Bonn, Germany
C Kramm

²Department of Paediaric Haematology/Oncology, University of Goettingen, Germany
A Waha

¹Institute of Neuropathology, University of Bonn, Germany
T Pietsch

¹Institute of Neuropathology, University of Bonn, Germany

Abstract

Full Text

Giant cell glioblastoma (G-GBM) is a rare variant of glioblastoma characterized by very large often multinucleated tumour cells. G-GBM occur most frequently de novo; in contrast to IDH wildtype GBM they carry TP53 mutations in high frequency. We performed a systematic (immuno)histological and genetic analysis by MIP, panel NGS and pyrosequencing in a cohort of 58 G-GBM (25 children, 33 adults). 78.4% of G-GBM carried mutations of TP53. Five G-GBM represented IDH-mutated gliomas, 5 cases had H3F3A-G34, and 3 had H3-K27 M mutations. The vast majority (75%) lacked IDH or histone gene mutations. In these, chromosome 7 showed a copy number gain in 2/3 of the cases. TERT promotor mutations occurred only in adult patients at a frequency of 35.5%. Chrom. 1q gain, 10 and 13 loss was more frequent in adults. MGMT promotor was methylated in 30.6% of G-GBM. As a potential therapeutic target, PDGFR-alpha was found expressed in most cases and its gene showed copy number gain in 34.5%. In summary, G-GBM is a histological phenotype most likely related to p53 dysfunction but can occur in different genetically defined GBM entities (IDH-, histone gene mutated or in IDH/histone wildtype GBM).