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Acta Neuropathol Commun. 2016 Jan 13;4:4. doi: 10.1186/s40478-015-0270-7.

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

Author information

1
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, 1648 Pierce Dr NE, Atlanta, GA, 30307, USA.
2
Biostatistics and Bioinformatics Shared Resource, Winship Cancer Institute of Emory University, 1365 Clifton Rd, Atlanta, GA, 30322, USA.
3
Department of Pathology, Northwestern University of Feinberg School of Medicine, 303 East Chicago Avenue Ward 3-140W127, Chicago, IL, 60611, USA.
4
Department of Biomedical Informatics, Emory University, 36 Eagle Row 5th Floor South, Atlanta, GA, 30322, USA.
5
Greenwood Genetics Center, JC Self Research Institute, 106 Gregor Mendel Circle, Greenwood, SC, 29646, USA.
6
Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, 1518 Clifton Road, Atlanta, GA, 30322, USA.
7
Department of Radiation Oncology, Emory University School of Medicine, 1648 Pierce Dr NE, Atlanta, GA, 30307, USA.
8
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, 1648 Pierce Dr NE, Atlanta, GA, 30307, USA. dbrat@emory.edu.
9
Department of Biomedical Informatics, Emory University, 36 Eagle Row 5th Floor South, Atlanta, GA, 30322, USA. dbrat@emory.edu.

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.

PMID:
26757882
PMCID:
PMC4711079
DOI:
10.1186/s40478-015-0270-7
[Indexed for MEDLINE]
Free PMC Article

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