TY - JOUR
T1 - Farewell to GBM-O
T2 - Genomic and transcriptomic profiling of glioblastoma with oligodendroglioma component reveals distinct molecular subgroups
AU - Hinrichs, Benjamin H.
AU - Newman, Scott
AU - Appin, Christina L.
AU - Dunn, William
AU - Cooper, Lee
AU - Pauly, Rini
AU - Kowalski, Jeanne
AU - Rossi, Michael R.
AU - Brat, Daniel J.
N1 - Funding Information:
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 Winship Cancer Tissue and Pathology Shared Resource, including Jennifer Shelton and Dianne Alexis, were instrumental in their assistance with this work. The work was also supported by NIH/NCI award R01 CA176659 (DJB).
PY - 2016/1/13
Y1 - 2016/1/13
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84987718350&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84987718350&partnerID=8YFLogxK
U2 - 10.1186/s40478-015-0270-7
DO - 10.1186/s40478-015-0270-7
M3 - Article
C2 - 26757882
AN - SCOPUS:84987718350
VL - 4
SP - 4
JO - Acta neuropathologica communications
JF - Acta neuropathologica communications
SN - 2051-5960
ER -