Abstract
IntroductionGlioblastoma 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.ResultsThree 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.ConclusionsOur 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s40478-015-0270-7) contains supplementary material, which is available to authorized users.
Highlights
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
Our results showed that despite having overlapping morphologic features, our GBM-O cohort was composed of three discrete molecular subgroups, each with characteristic coding variants, copy-number aberrations (CNAs) and gene expression patterns
Previous investigations have attempted to clarify the significance of GBM-O through molecular testing
Summary
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, one secondary) cases. Glioblastoma (GBM) is the highest grade infiltrating astrocytoma and the World Health Organization (WHO) recognizes several morphologic patterns. Glioblastoma with Oligodendroglioma component (GBM-O), WHO grade IV, was recently described as a diffusely infiltrative, Prior studies suggested that GBM-O is enriched for IDH mutations and has fewer PTEN deletions than other forms of GBM [2]. In order to better characterize GBM-O, we performed copy number microarray, whole transcriptome RNA-sequencing and gene panel deep sequencing
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