Farewell to GBM-O: Genomic and transcriptomic profiling of glioblastoma with oligodendroglioma component reveals distinct molecular subgroups.

• Type of Material: Article
• Authors: Benjamin H. Hinrichs, Emory University; Scott Newman, Emory University; Christina L. Appin, Northwestern University of Feinberg School of Medicine; William Dunn, Emory University; Lee Cooper, Emory University; Rini Pauly, Greenwood Genetics Center; Jeanne Kowalski, Emory University; Michael Rossi, Emory University; Daniel Brat, Emory University
• Language: English
• Date: 2016
• Publisher: BioMed Central
• Publication Version: Final Published Version
• Copyright Statement: © Hinrichs et al. 2016
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1186/s40478-015-0270-7
• Title of Journal or Parent Work: Acta Neuropathologica Communications
• ISSN: 2051-5960
• Volume: 4
• Issue: 1
• Start Page: 4
• End Page: 4
• Grant/Funding Information: The Winship Cancer Tissue and Pathology Shared Resource, including Jennifer Shelton and Dianne Alexis, were instrumental in their assistance with this work.; Research reported in this publication was supported in part by the Biostatistics and Bioinformatics Shared resource of Winship Cancer Institute of Emory University and NIH/NCI under award number P30CA138292.; The work was also supported by NIH/NCI award R01 CA176659 (DJB).
• Research Categories: Health Sciences, Oncology; Health Sciences, Radiology

Abstract

INTRODUCTION: Glioblastoma with oligodendroglioma component (GBM-O) was recognized as a histologic pattern of glioblastoma (GBM) by the World Health Organization (WHO) in 2007 and is distinguished by the presence of oligodendroglioma-like differentiation. To better understand the genetic underpinnings of this morphologic entity, we performed a genome-wide, integrated copy number, mutational and transcriptomic analysis of eight (seven primary, primary secondary) cases. RESULTS: Three GBM-O samples had IDH1 (p.R132H) mutations; two of these also demonstrated 1p/19q co-deletion and had a proneural transcriptional profile, a molecular signature characteristic of oligodendroglioma. The additional IDH1 mutant tumor lacked 1p/19q co-deletion, harbored a TP53 mutation, and overall, demonstrated features most consistent with IDH mutant (secondary) GBM. Finally, five tumors were IDH wild-type (IDHwt) and had chromosome seven gains, chromosome 10 losses, and homozygous 9p deletions (CDKN2A), alterations typical of IDHwt (primary) GBM. IDHwt GBM-Os also demonstrated EGFR and PDGFRA amplifications, which correlated with classical and proneural expression subtypes, respectively. CONCLUSIONS: Our findings demonstrate that GBM-O is composed of three discrete molecular subgroups with characteristic mutations, copy number alterations and gene expression patterns. Despite displaying areas that morphologically resemble oligodendroglioma, the current results indicate that morphologically defined GBM-O does not correspond to a particular genetic signature, but rather represents a collection of genetically dissimilar entities. Ancillary testing, especially for IDH and 1p/19q, should be used for determining these molecular subtypes.