Molecular characteristics of glioblastoma with 1p/19q co-deletion.
Recent developments in molecular analysis have revealed genetic alterations in human gliomas. Loss of heterozygosity (LOH) is a critical molecular marker for classification of human glioma, and is useful for predicting outcome. Our previous LOH study identified a small subgroup of glioblastoma (GBM), with 1p/19q co-deletion, with a favorable clinical outcome. In this study, we investigated molecular pathological features of eight GBM with 1p/19q co-deletion compared with "classic" GBM and anaplastic oligodendroglioma (AO). We estimated EGFR gene amplification, EGFRvIII expression, CDKN2A (p16) homozygous deletion, and isocitrate dehydrogenase 1/2 (IDH1/2) gene mutations. We also conducted an analysis of the expression of proneural genes (DLL3, OLIG2, SOX2). On histopathological review, only one GBM was diagnosed as glioblastoma with oligodendroglioma component (GBMO). Loss of chromosomes 10 and 17p is common, and neither IDH1/2 mutations nor EGFRvIII expression were detected in GBM with 1p/19q co-deletion. The expression profile revealed high expression of the OLIG2 gene in this subgroup. High expression of proneural gene OLIG2 without EGFRvIII expression may be associated with a favorable clinical outcome; however, IDH1/2 gene status and the extent of LOH regions may indicate that this small subgroup of GBM is a distinct genetic subgroup from oligodendroglial tumors.
Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan. mmizoguc@ns.med.kyushu-u.ac.jp
Masahiro
M
Mizoguchi
Koji
K
Yoshimoto
Xinlong
X
Ma
Yanlei
Y
Guan
Nobuhiro
N
Hata
Toshiyuki
T
Amano
Akira
A
Nakamizo
Satoshi O
SO
Suzuki
Toru
T
Iwaki
Tomio
T
Sasaki
D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics*; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics; D017353:Gene Deletion; D005909:Glioblastoma / Q000235:genetics*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D019656:Loss of Heterozygosity; D009419:Nerve Tissue Proteins / Q000235:genetics; D000076104:Oligodendrocyte Transcription Factor 2; D060888:Real-Time Polymerase Chain Reaction; D059467:Transcriptome
D051792:Basic Helix-Loop-Helix Proteins; D066246:ErbB Receptors; D007521:Isocitrate Dehydrogenase; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; C405708:OLIG2 protein, human; C410723:epidermal growth factor receptor VIII; C538784:IDH2 protein, human; C543588:IDH1 protein, human